Request History

• Restore to current request
• applications/view/1408
• applications/view/624
• applications/view/1396
• applications/view/1378

Session

• Config(array)
  • userAgent9c3d2c89526db53b7b69e8c9faa06145
  • time1776437857
  • countdown10

Request

Cake Params

• plugin(null)
• controllerapplications
• actionindex
• named(array)
  • page20
  • sortstudy_title
  • directionasc
• pass(empty)
• isAjax(false)
• paging(array)
  • Application(array)
    • page20
    • current5
    • count559
    • prevPage(true)
    • nextPage(true)
    • pageCount112
    • order(array)
      • Application.study_titleasc
    • limit5
    • options(array)
      • page20
      • order(array)
        • Application.study_titleasc
      • sortstudy_title
      • directionasc
    • paramTypenamed

Post data

• Application(empty)

Query string

No querystring data.

Cookie

To view Cookies, add CookieComponent to Controller

Current Route

• keys(array)
  • 0controller
  • 1action
• options(empty)
• defaults(array)
  • plugin(null)
• template/:controller/:action/*

Sql Logs

Logs

View Variables

• trial_statuses(array)
  • 1Recruiting
  • 2Not yet recruiting
  • 3Suspended
  • 4Stopped
  • 5Completed
  • 6In follow-up
  • 7Analysing
  • 8Writing-up
  • 9Application withdrawn
  • 10Ongoing Closeout Phase
• applications(array)
  • 0(array)
    • Application(array)
      • id612
      • user_id94
      • trial_status_id8
      • abstract_of_study<p>\n Current WHO-recommended treatment for Visceral Leishmaniasis (VL) in Eastern Africa is a combination of Sodium Stibogluconate (SSG) and paromomycin (PM) administered for 17 days, with an efficacy of 91%. This treatment is far from optimal as it requires 17 days of two separate painful injections, necessitating patients to be hospitalized during the whole treatment period. In addition, the antimonial SSG exhibits life-threatening toxicities such as cardiotoxicity, hepatotoxicity and pancreatitis. Therefore, there is an urgent need to explore alternatives that are efficacious, safe, ideally of short duration, affordable and suitable to be used in remote areas where VL occurs.</p>\n<p>\n Until new chemical entities are developped, opportunities with currently available compounds should be assessed to improve on current treatment options, with the main aim to replace the toxic and patient-unfriendly SSG treatment-component.</p>\n<p>\n Miltefosine (MF) is the only oral drug available for VL treatment. It has been extensively used in Asia for VL treatment as monotherapy for 28 days, with satisfactory cure rates (>90%). However, MF as monotherapy showed lower efficacy in Eastern Africa (72%, 95%CI: 60–85%) than in Asia. PK data indicated under-exposure and higher relapse rates in children compared to adults with the conventional linear 2.5 mg/kg/day MF dose. To overcome this under-dosage in children, an allometrically scaled dosing regimen has been developed. This allometric dosage was assessed for paediatric VL in the LEAP 0714 trial in Kenya and Uganda. The 28 days regimen of MF allometric dose showed a cure rate of 90.0% (95% CI: 73.5-97.9%) at 6 months follow up in a population of 30 patients aged 4 to 12 years. These results showed that the efficacy level could be increased in children treated with the allometric dose, reaching similar efficacy observed in adults (i.e. 86.2%). </p>\n<p>\n PM has been well studied in Eastern Africa during the development of the combination SSG-PM. PM monotherapy of 20mg/kg/d IM for 21 days showed an overall efficacy at 6 months of 84.3%. Intramuscular PM can be administered at primary health care level, requires minimal training of health personnel and the drug can be stored at room temperature.</p>\n<p>\n Replacing the toxic SSG with oral MF can bring better safety and a more field-adapted, patient-friendly treatment.</p>\n<p>\n The current study aims to determine the safety and efficacy of two combination regimens of PM and MF as compared to SSG-PM for the treatment of primary VL patients in Eastern Africa.  This will be an open label, Phase III, randomized controlled, parallel arm multicentre non-inferiority clinical trial. The study treatments are:</p>\n<ul>\n <li>\n Arm 1: Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing BID for 14 days</li>\n <li>\n Arm 2: Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing BID for 28 days</li>\n</ul>\n<p>\n The control arm is the current standard treatment for VL in East Africa:</p>\n<ul>\n <li>\n Arm 3: Sodium Stibogluconate 20 mg/kg/day IM/IV combined with Paromomycin 15 mg/kg/day IM for 17 days</li>\n</ul>\n<p>\n MF allometric dosing will be calculated according to patient’s weight, height and sex. For patients weighing < 30 kg, an easy-to-use table with allometric dosing scheme by weight, height and sex will be provided to the investigators to define the exact daily dose to be administered. For patients weighing ≥ 30 kg, the allometric dose will correspond to the conventional dose in mg/kg. Therefore, patients weighing ≥ 30 to 44 kg will receive 100 mg/day and patients ≥ 45 kg will receive 150 mg/day.</p>\n<p>\n Subjects will be hospitalized for 14 days of PM and MF treatment in both arm 1 and arm 2.  MF treatment will start at the same time as PM treatment. At discharge (on day 15), patients allocated to arm 2 will be instructed to continue MF treatment on an out-patient basis until completion of the 28 days treatment. Subjects will receive clear instructions as well as a daily diary to guide them in their treatment schedule at home.</p>\n<p>\n SSG-PM combination therapy will be administered for 17 days according to routine VL treatment guidelines and patients will remain hospitalized for the entire duration of the treatment.</p>\n<p>\n The target population will be primary VL patients from 4 to 50 years. It is important to include a paediatric population which is particularly vulnerable and is a major factor in the East African disease burden. The trial will be run in the VL endemic countries at 6 LEAP sites: Kimalel and Kacheliba in Kenya, Amudat in Uganda, Doka and Um El Kher in Sudan and Gondar in Ethiopia.  </p>\n<p>\n Enrollment targe is 576 patients, 192 in each arm. Each patient’s participation in the study will be for approximately 7 months. This will consist of baseline assessments, treatment period (14, 17 or 28 days) and 6 months follow-up. Recruitment for the entire trial is expected to take 14 to 17 months assuming that 30 to 35% of all VL patients will meet the eligibility criteria. Therefore, study duration (first patient in to last patient, last visit) is expected to take approximately 24 months. Taking into account the analysis and reporting period, the study shall last at most 31 months.</p>\n<p>\n Primary efficacy endpoint will be the cure at day 210, based on clinical examination only (absence of clinical signs and symptoms of VL and no requirement for rescue treatment during the trial).</p>\n<p>\n Safety assessments will be done through routine monitoring of adverse events. A characterization of the nature and frequency of SAEs, AEs that lead to treatment discontinuation and overall frequency and severity of AEs from start of the treatment until 6 months follow-up will be made.</p>\n<p>\n Pharmacokinetics (PK) profile of PM and MF will be described and parasite clearance in each arm as indicated by direct microscopy and quantitative polymerase chain reaction (qPCR) will be evaluated as pharmacodynamics (PD) markers of cure. The relationship between PK and PD measurements will be further assessed through drug exposure-response modelling.</p>\n<p>\n Finally, compliance to MF treatment in an outpatient setting will also be assessed. If proven non-inferior to SSG-PM, the combination of PM and MF is expected to improve significantly treatment safety and to reduce pain, while ensuring low cost and suitability to be used in remote areas. It will provide the East African region with the first non-antimony-based effective treatment for VL.</p>\n
      • study_title<p align=\"center\">\n <span style=\"font-size:14px;\"><strong>An Open </strong><strong>Label</strong><strong>, Phase III, Randomized Controlled, </strong><strong>Multicentre</strong><strong> Non-Inferiority Trial </strong><strong>to</strong><strong> Compare Efficacy and Safety </strong><strong>of Miltefosine and </strong><strong>Paromomycin with Sodium Stibogluconate and Paromomycin Combination for Treatment </strong><strong>of</strong><strong> Primary Visceral Leishmaniasis (VL) Patients </strong><strong>in</strong><strong> Eastern </strong><strong>Africa</strong></span></p>\n<p>\n  </p>\n
      • laymans_summary<p>\n  </p>\n<p align=\"center\">\n <strong><u>LAY SUMMARY OF PROTOCOL FOR SERU SUBMISSION</u></strong></p>\n<p align=\"center\">\n  </p>\n<p>\n <strong>Protocol Title:</strong> An open-label, Phase lll, randomized controlled multicenter non-inferiority trial to compare efficacy and safety of Miltefosine and paromomycin with sodium stibogluconate and Paromomycin combination for treatment of primary visceral leishmaniasis patients in Eastern Africa</p>\n<p>\n <strong>Institutions and Investigators:</strong></p>\n<ol>\n <li>\n Kenya Medical Research Institute - Dr. Jane Mbui, Dr. Simon Njenga</li>\n <li>\n Kimalel Health Centre: Dr. Peter Kioko</li>\n <li>\n Kacheliba Sub-District Hospital: Mark Riongoita</li>\n</ol>\n<p>\n  </p>\n<p>\n <strong>Sponsor</strong>: Drugs for Neglected Diseases <em>initiative</em> (DNDi), 15 Chemin Louis Dunant, 1202 Geneva, Switzerland</p>\n<p>\n <strong>Protocol Summary:</strong></p>\n<p>\n The current treatment for Kala-azar in East Africa is Sodium Stibogluconate (SSG) with Paromomycin (PM) for 17 days. This treatment requires 2 injections every day for 17 days in the hospital. The injections are painful and can affect the heart, liver, and pancreas. This study is being done to find better treatments that take fewer days, are effective, safer, less painful, affordable and easy for use in remote areas.</p>\n<p>\n This study aims to determine the safety and efficacy (how well a treatment works) of two combination regimens of PM and Miltefosine (MF) as compared to SSG-PM for the treatment of Kala-azar in patients in Eastern Africa.  Miltefosine is taken by mouth while SSG and PM are given by injection.</p>\n<p>\n There will be three treatment groups. Two groups will receive PM+MF combination for 14 days with one of them extending MF until 28 days. A third group will receive SSG and PM combination for 17 days.</p>\n<ul>\n <li>\n Group 1: Paromomycin injection for 14 days combined with Miltefosine by mouth 2 times a day for 14 days</li>\n</ul>\n<p>\n  </p>\n<ul>\n <li>\n Group 2: Paromomycin injection for 14 days combined with Miltefosine by mouth 2 times  a day for 28 days</li>\n</ul>\n<ul>\n <li>\n Group 3: Sodium Stibogluconate injection combined with Paromomycin injection for 17 days\n <ul style=\"list-style-type:circle;\">\n <li>\n <em>Note: Group 3 is called the control group</em> – it is the current standard treatment for Kala-azar in East Africa</li>\n </ul>\n </li>\n</ul>\n<p>\n  </p>\n<p>\n In this study each patient’s treatment will be allocated randomly by chance, equally between the 3 treatment groups being tested and each patient will know what treatment they will receive.</p>\n<p>\n All patients will get the treatments in the hospital except patients in the group receiving Miltefosine for 28 days who will take the remaining medicines at home after they are discharged when they finish their PM and MF for 14 days.</p>\n<p>\n The study will allow us to compare how the treatments work, know which PM and MF combination is better, how safe the treatments are and how regularly patients take the medicines at home.</p>\n<p>\n <strong>Study population and duration of the study</strong></p>\n<p>\n The target population for this study is patients who are being diagnosed with Kala-azar for the first time and who have never been treated for Kala-azar. These patients will range from 4 to 50 years old. It is important to include children in this study because they are particularly at risk of this disease and contribute to the disease burden in the Eastern African region.</p>\n<p>\n The study will enroll a total of 576 patients in Kenya, Sudan, Ethiopia and Uganda where Kala-azar affects the population. Each of the 3 treatment groups will have 192 patients. There are 6 hospitals involved in the study: Kimalel, and Kacheliba in Kenya; Amudat in Uganda; Gondar in Ethiopia and Dooka and Um El Kheir in Sudan. Participation for each patient in the study will be around 7 months from the day of enrollment until the last study visit. The study itself will last about 2 years from the first patient enrolled until the last patient has finished their last visit and the study is closed.</p>\n<p>\n <strong>Procedures during the study</strong></p>\n<p>\n Each study participant will stay in the hospital for about 2-3 weeks depending on their treatment group. During study participation, the patient will have assessments done before starting the study medication, followed by the treatment period of either 14, 17 or 28 days and 6 months of follow up after completing treatment. During the treatment period, patients will be seen in the clinic on Day 1, 3, 7, 14. Some patients in treatment group 2 will also be seen on day 21 to check the amount of Paramomycin in their blood. After discharge patients will come for follow up visits from home, 28 days after treatment start, 1 month after treatment start and at 6 months after the end of treatment.</p>\n<p>\n The health care workers will closely monitor the safety of the patients throughout the study by checking for any medical illness or any reactions that may or may not be related to the study treatments. If deemed necessary, treatment may be interrupted to ensure the safety of the patient. All safety events will be recorded, followed closely and treated appropriately for resolution of the event.</p>\n<p>\n Patients will have blood collected for measurement of the levels of the Miltefosine in their blood on day 28 and day 56 in order to assess if they have taken their drugs consistently and correctly as recommended.</p>\n<p>\n In Kenya and Sudan, 40 patients (20 children and 20 adults) in treatment groups 1 and 2 will have blood collected for measurement of drug (MF and PM) levels more frequently during the treatment period.</p>\n<p>\n The amount of parasite in the blood and bone marrow or spleen will be checked to assess how well the different treatments work and compare the response with the different treatments. The amount of parasite will also be checked in the follow up period if it is suspected that the patient has had a relapse of disease.</p>\n<p>\n Finally, adherence to MF treatment in an outpatient setting will also be assessed. If it is proven that MF and PM combination works as well as the combination of SSG and PM, the combination of PM and MF is expected to significantly improve treatment safety and to reduce pain, while ensuring low cost and suitability to be used in remote areas.</p>\n
      • short_titleMF/PM Phase III
      • protocol_noECCT/17/06/01
      • version_no1.0
      • date_of_protocol20-02-2017
      • study_drugMiltefosine (Impavido), Paromomycin, Sodium Stibogluconate
      • disease_conditionPrimary Visceral Leishmaniasis
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameMiltefosine, Paromomycin, Sodium Stibogluconate
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjmalongo@dndi.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget0
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantGina Ouattara
      • declaration_date116-06-2017
      • declaration_principal_investigatorJane Mbui
      • declaration_date216-06-2017
      • placebo_presentNo
      • study_objectives<p>\n <br />\n Objectives<br />\n Primary Objective<br />\n • To compare the efficacy of two combination regimens of PM (14 days) and MF (14 or 28 days) with the standard 17-day course of SSG-PM for the treatment of primary VL patients in Eastern Africa<br />\n Secondary Objectives<br />\n • To compare the safety of two combination regimens of PM (14 days) and MF (14 or 28 days) with the standard 17-day course of SSG-PM<br />\n • To describe the pharmacokinetic (PK) profiles of PM and MF (14 days and 28 days regimen) in primary VL patients<br />\n • To evaluate parasite clearance in each arm as indicated by direct microscopy and quantitative polymerase chain reaction (qPCR)<br />\n • To assess the relationship between PK and PD measurements (parasitological and clinical outcome)<br />\n • To assess compliance to MF treatment in an outpatient setting</p>\n
      • principal_inclusion_criteria<ul>\n <li>\n Patients with clinical signs and symptoms of VL and confirmatory parasitological microscopic diagnosis</li>\n <li>\n Patients aged 4 to <u><</u> 50 years who are able to comply with the study protocol.</li>\n <li>\n Patients for whom written informed consent has been obtained (if aged 18 years and over) or signed by parents(s) or legal guardian for patients under 18 years of age. In the case of minors, assent from the children also needs to be obtained as per each country regulatory requirements</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Patients who are relapse cases</li>\n <li>\n Patients with Para-Kala azar dermal leishmaniasis</li>\n <li>\n Patients who have received any anti-leishmanial drugs in the last 6 months</li>\n <li>\n Patients with severe malnutrition (for children aged <5 years: weight-for-height WHO reference curves by sex, z score <-3; for children 5-18 years: BMI-for-age WHO reference curves by sex, z score < -3; for adults >18 years: BMI < 16)</li>\n <li>\n Patients with positive HIV diagnosis</li>\n <li>\n Patients with previous history of hypersensitivity reaction or known drug class allergy to any of the study treatments</li>\n <li>\n Patients with previous history of cardiac arrhythmia or with a clinically significant abnormal ECG</li>\n <li>\n Patients suffering from a concomitant severe infection such as TB or any other serious underlying disease (cardiac, renal, hepatic) which would preclude evaluation of the patient’s response to study medication</li>\n <li>\n Patients suffering from other conditions associated with splenomegaly such as schistosomiasis</li>\n <li>\n Pregnant or lactating women</li>\n <li>\n Female patients of child bearing age who do not accept to have a pregnancy test done at screening and/or who do not agree to use contraception from treatment period until 5 months after the end of treatment (see section 15.2)</li>\n <li>\n Patients with haemoglobin < 5g/dl</li>\n <li>\n Patients with WBC < 1 x 10³/mm³</li>\n <li>\n Patients with platelets < 40,000/mm³</li>\n <li>\n Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range</li>\n <li>\n Patients with total bilirubin more than 1.5 times the upper normal range</li>\n <li>\n Patients with serum creatinine above the ULN for age and sex</li>\n <li>\n Patients with clinical signs of severe VL disease such as jaundice and bleeding</li>\n <li>\n Patients with pre-existing clinical hearing loss based on audiometry at baseline</li>\n <li>\n Patients who cannot comply with the planned scheduled visits and procedures of the study protocol</li>\n</ul>\n
      • primary_end_points<p>\n <em>Definitive cure</em> - cure at 6 months follow up defined as absence of clinical signs and symptoms of VL at D210 and no requirement for rescue treatment during the trial (e.g. no relapse or initial treatment failure).</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <u><strong>KIMALEL SITE</strong></u></p>\n<p>\n <u><strong>Investigators:</strong></u></p>\n<ul>\n <li>\n Dr. Jane Mbui, MBChB, Mmed Internal Medicine – Principal Investigator</li>\n <li>\n Dr. Simon Njoroge, MBChB, Mmed Pediatrics – Co-Principal Investigator</li>\n</ul>\n<p>\n <strong><u>Site Investigators:</u></strong></p>\n<ul>\n <li>\n Dr. Peter Kioko – Medical Doctor (MBChB)</li>\n <li>\n Jonathan Chebotibin – Study Nurse (KRCHN)</li>\n <li>\n Bernard Kipkemboi Chepkwony - Study Pharmacist (Diploma in Pharmaceutical Technology)</li>\n</ul>\n<p>\n <strong><u>Site Facilities:</u></strong></p>\n<p>\n Kimalel health centre is a Ministry of Health hospital located in rift valley province, Baringo County, Marigat district, Kenya. The Kimalel hospital has a VL treatment centre with a 22 bed ward within the hospital.</p>\n<p>\n Previously, the site was managed by Medicines San Frontiers (MSF) but currently DNDi supports treatment at the kala azar treatment centre in this facility. The Kala Azar treatment centre has the objective to provide access to Diagnostics and Treatment for VL for the surrounding community. The treatment center treats approximately 200 patients/year. DNDi rehabilitated the hospital for clinical trial purposes and purchased an ambulance.</p>\n<p>\n Outpatient registration Desk - As per MOH procedure, all patients received in the clinic are registered in the Outpatient register and given an Outpatient number. The patients then receive a ‘General Outpatient Record’ card which is retained in the hospital as copy of the outpatient records. The outpatient record also becomes source document to record the Past Medical History and will be used for any future visits by the patient. The patient is also given ‘Kimalel Sub-District Hospital Attendance Card’ for future appointments.</p>\n<p>\n Clinical Officer’s Room- All patients are then referred to the Clinical Officer’s room for consultation, diagnosis and treatment. A decision is taken to treat, discharge or admit the patient depending on their medical condition. Patients suspected of Visceral Leishmaniasis have blood taken for Full Hemogram (Complete Blood Count) and PTI (Prothrombin Time Index). The patient is then admitted to the ward pending lab results and further investigation unless the picture from the CBC/PTI is not suggestive of VL. The Clinical Officer’s room serves as the phlebotomy room and initial Vital Signs observation station.</p>\n<p>\n Observation Room – After the Clinical Officer review, the patients is referred to the observation room. As per MOH procedure, all patients admitted are given an in-patient number. Patients with suspected VL will undergo pre-admission observations performed by the nurse. The in-patient file is opened and the patient is then taken to the ward.</p>\n<p>\n Male/Female Ward – After the patient has been registered for admission, they receive an in-patient number and file, patients suspected of VL undergo the full informed consent process. Once the patient has signed the informed consent, the patient receives a CCR number (equivalent to Study Participant number). The patients consented are entered into the screening log. The patient then receives a Study File and may now undergo a Spleen Aspirate for parasitology and inclusion/exclusion procedures as defined in the protocol. If the patient qualifies for the study, he/she is admitted in the ward and treatment commences.</p>\n<p>\n The study site will has the capacity to conduct the screening and safety laboratory tests. These include HIV testing, Hematology and Biochemistry analysis.</p>\n<p>\n  </p>\n<p>\n <u><strong>KACHELIBA SITE</strong></u></p>\n<p>\n <u>Investigators:</u></p>\n<ul>\n <li>\n Dr. Jane Mbui, MBChB, Mmed Internal Medicine – Principal Investigator</li>\n <li>\n Dr. Simon Njoroge, MBChB, Mmed Pediatrics – Co-Principal Investigator</li>\n</ul>\n<p>\n <u>Site Investigators:</u></p>\n<ul>\n <li>\n Mark Riongoita -Clinician (Diploma in clinical medicine and surgery)</li>\n <li>\n Charity Maingi – Study Nurse (KRN, KRM, KRPHN, BSc Nursing, MPH Epidemiology)</li>\n <li>\n Songio Kosgei Kipchirchir - Study Pharmacist (Diploma in Pharmaceutical Technology)</li>\n</ul>\n<p>\n <u>Site Facilities:</u></p>\n<p>\n Kacheliba sub district hospital is a Ministry of Health hospital located in Kacheliba, North Pokot District, West Pokot County, Kenya. The Kacheliba hospital has a VL treatment centre with a 50 bed ward within the hospital. DNDi supports treatment at the kala azar treatment centre in this facility. The Kala azar treatment centre has the objective to provide access to Diagnostics and Treatment for VL for the surrounding community.The treatment centre treats approximately 500 patients/year.</p>\n<p>\n Registration, outpatient clinic and ward: All patients received in the clinic are registered in the outpatient register and given an outpatient number.  All patients are referred to the clinician’s room for consultation, diagnosis and treatment. Patients who are suspected to have VL have blood samples taken for full hemogram (Complete Blood Count) and Prothrombin Time Index (PTI).  Patient is then admitted to the ward pending lab results.   Once the patient is confirmed to have VL and meet the inclusion exclusion criteria, informed consent form will be administered by the nurse or clinical officer in the kala azar treatment room.</p>\n<p>\n Observation room: After obtaining the informed consent, patient’s anthropometric data will be obtained within the kala azar treatment room. This room will also double as a storage area for Case Report Forms and the source documents.  The facility has a kala-azar suspect patient file where all patient information will be recorded.</p>\n<p>\n Male/female ward: Once patient is enrolled in the study, they will be admitted in the ward and treatment commenced.  During the hospitalization period, they will be reviewed by the study staff daily until they are discharged.</p>\n<p>\n The study site has the capacity to conduct the screening and safety laboratory tests. These include HIV testing, Hematology, Biochemistry analysis. The lab was  upgraded prior to the conduct of the previous Miltefosine trial.  New equipment was  installed, validated and commissioned for these purposes.  These equipment are still at site and will be used in this new trial. </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n This trial will be conducted in Kenya, Uganda, Sudan and Ethiopia, which are affected by Visceral Leishmaniasis (VL).  VL does not occur in Switzerland which is the sponsor host country.</p>\n<p>\n Eastern Africa is expected to become the VL region with the highest burden worldwide for global VL control, following significant VL elimination efforts in Southeast Asia.</p>\n<p>\n WHO revised the recommended VL treatment for Eastern Africa in 2010 from sodium stibogluconate (SSG) monotherapy (30 days treatment) to a combination of SSG and PM administered for 17 days, following a phase III trial conducted in the region (WHO, 2010). The efficacy of SSG-PM combination was 91% in the intention to treat population using a complete case analysis, which was non-inferior to a 30-day SSG monotherapy (Musa et al., 2012; Hailu et al., 2010). This new treatment is an improvement over the 30-day SSG monotherapy, but a few important drawbacks and limitations still preclude its general use. Although the treatment regimen is shorter, it still requires 17 days of two separate painful injections, necessitating patients to be hospitalized during the whole treatment period. In addition, there are life-threatening toxicities associated with the use of antimony-based treatments such as SSG. These include cardiotoxicity, hepatotoxicity and pancreatitis.</p>\n<p>\n AmBisome® (liposomal amphotericin B) is used as 2^nd line drug for rescue treatment and for specific target populations such as pregnant women, severe disease or HIV co-infection. The need for cold chain, high cost and the administration by well trained personnel limit the widespread use of AmBisome® in Eastern Africa.</p>\n<p>\n Therefore, there is a need to explore alternatives that are efficacious, safe, ideally of short duration, affordable and suitable to be used in remote areas where VL occurs. In this context, an oral efficacious and safe treatment would be more adapted to field conditions and would allow shorter hospitalization time.</p>\n<p>\n As we wait for the New Chemical Entities, new opportunities with currently available compounds should be assessed to improve on current treatment options, with the main aim to replace the toxic and patient-unfriendly SSG treatment-component.</p>\n
      • other_details_regulatory_notapproved<p>\n National Drug Authority - Uganda</p>\n<p>\n Application date: 7th April 2017</p>\n
      • other_details_regulatory_approved<p>\n None yet</p>\n
      • other_details_regulatory_rejected<p>\n None have rejected the trial so far</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_durationRecruitment for the entire trial is expected to take 14 - 17 months. Each patients participation in the study will be for approximately 7 months. Therefore the study duration (first patient in to last patient last visit) will be approximately 24 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard of care treatmen
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites2
      • multi_country_listKenya, Uganda, Sudan, Ethiopia
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKacheliba - approx. 15 participants per month\nKimalel - approx. 10 participants per month\nRecruitment for entire trial expected to take 14 - 17 months
      • total_participants_worldwide576
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyAll participants will be patients who require treatment for Visceral Leishmaniasis.\nAny woman of child bearing potential has to consent to use depoprovera contraception in order to be eligible to participate in the trial.\nChildren from 4 years of age upwards will be enrolled into the clinical trial based on consent from their parents. Children aged 12 yrs to < 18 years will give assent to participate in addition to consent from their parent/guardian
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJane
      • investigator1_middle_name
      • investigator1_family_nameMbui
      • investigator1_qualificationMBChB, MMed (Internal Medicine), MSc Epidemiology
      • investigator1_professional_addressCentre for Clinical Research Kenya Medical Research Institute
      • investigator1_telephone+254 20 2722541 ext 3211 (office) +254 722 755358 (mobile)
      • investigator1_emailjmbui@kemri.org
      • organisations_transferred_No
      • number_participantsDue to competitive enrolment between the 4 countries involve, approximately 150 patients, but could be less or more depending on speed of enrolment across the 4 countries.
      • notification
      • approval_date04-10-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n <strong>Protocol Title:</strong> An open-label, Phase lll, randomized controlled multicenter non-inferiority trial to compare efficacy and safety of Miltefosine and paromomycin with sodium stibogluconate and Paromomycin combination for treatment of primary visceral leishmaniasis patients in Eastern Africa</p>\n<p>\n <strong>Institutions and Investigators:</strong></p>\n<ol>\n <li>\n Kenya Medical Research Institute - Dr. Jane Mbui, Dr. Simon Njenga</li>\n <li>\n Kimalel Health Centre: Dr. Peter Kioko</li>\n <li>\n Kacheliba Sub-District Hospital: Mark Riongoita</li>\n</ol>\n<p>\n  </p>\n<p>\n <strong>Sponsor</strong>: Drugs for Neglected Diseases <em>initiative</em> (DNDi), 15 Chemin Louis Dunant, 1202 Geneva, Switzerland</p>\n<p>\n <strong>Protocol Summary:</strong></p>\n<p>\n The current treatment for Kala-azar in East Africa is Sodium Stibogluconate (SSG) with Paromomycin (PM) for 17 days. This treatment requires 2 injections every day for 17 days in the hospital. The injections are painful and can affect the heart, liver, and pancreas. This study is being done to find better treatments that take fewer days, are effective, safer, less painful, affordable and easy for use in remote areas.</p>\n<p>\n This study aims to determine the safety and efficacy (how well a treatment works) of two combination regimens of PM and Miltefosine (MF) as compared to SSG-PM for the treatment of Kala-azar in patients in Eastern Africa.  Miltefosine is taken by mouth while SSG and PM are given by injection.</p>\n<p>\n There will be three treatment groups. Two groups will receive PM+MF combination for 14 days with one of them extending MF until 28 days. A third group will receive SSG and PM combination for 17 days.</p>\n<ul>\n <li>\n Group 1: Paromomycin injection for 14 days combined with Miltefosine by mouth 2 times a day for 14 days</li>\n</ul>\n<p>\n  </p>\n<ul>\n <li>\n Group 2: Paromomycin injection for 14 days combined with Miltefosine by mouth 2 times  a day for 28 days</li>\n</ul>\n<ul>\n <li>\n Group 3: Sodium Stibogluconate injection combined with Paromomycin injection for 17 days\n <ul>\n <li>\n <em>Note: Group 3 is called the control group</em> – it is the current standard treatment for Kala-azar in East Africa</li>\n </ul>\n </li>\n</ul>\n<p>\n  </p>\n<p>\n In this study each patient’s treatment will be allocated randomly by chance, equally between the 3 treatment groups being tested and each patient will know what treatment they will receive.</p>\n<p>\n All patients will get the treatments in the hospital except patients in the group receiving Miltefosine for 28 days who will take the remaining medicines at home after they are discharged when they finish their PM and MF for 14 days.</p>\n<p>\n The study will allow us to compare how the treatments work, know which PM and MF combination is better, how safe the treatments are and how regularly patients take the medicines at home.</p>\n<p>\n <strong>Study population and duration of the study</strong></p>\n<p>\n The target population for this study is patients who are being diagnosed with Kala-azar for the first time and who have never been treated for Kala-azar. These patients will range from 4 to 50 years old. It is important to include children in this study because they are particularly at risk of this disease and contribute to the disease burden in the Eastern African region.</p>\n<p>\n The study will enroll a total of 576 patients in Kenya, Sudan, Ethiopia and Uganda where Kala-azar affects the population. Each of the 3 treatment groups will have 192 patients. There are 6 hospitals involved in the study: Kimalel, and Kacheliba in Kenya; Amudat in Uganda; Gondar in Ethiopia and Dooka and Um El Kheir in Sudan. Participation for each patient in the study will be around 7 months from the day of enrollment until the last study visit. The study itself will last about 2 years from the first patient enrolled until the last patient has finished their last visit and the study is closed.</p>\n<p>\n <strong>Procedures during the study</strong></p>\n<p>\n Each study participant will stay in the hospital for about 2-3 weeks depending on their treatment group. During study participation, the patient will have assessments done before starting the study medication, followed by the treatment period of either 14, 17 or 28 days and 6 months of follow up after completing treatment. During the treatment period, patients will be seen in the clinic on Day 1, 3, 7, 14. Some patients in treatment group 2 will also be seen on day 21 to check the amount of Paramomycin in their blood. After discharge patients will come for follow up visits from home, 28 days after treatment start, 1 month after treatment start and at 6 months after the end of treatment.</p>\n<p>\n The health care workers will closely monitor the safety of the patients throughout the study by checking for any medical illness or any reactions that may or may not be related to the study treatments. If deemed necessary, treatment may be interrupted to ensure the safety of the patient. All safety events will be recorded, followed closely and treated appropriately for resolution of the event.</p>\n<p>\n Patients will have blood collected for measurement of the levels of the Miltefosine in their blood on day 28 and day 56 in order to assess if they have taken their drugs consistently and correctly as recommended.</p>\n<p>\n In Kenya and Sudan, 40 patients (20 children and 20 adults) in treatment groups 1 and 2 will have blood collected for measurement of drug (MF and PM) levels more frequently during the treatment period.</p>\n<p>\n The amount of parasite in the blood and bone marrow or spleen will be checked to assess how well the different treatments work and compare the response with the different treatments. The amount of parasite will also be checked in the follow up period if it is suspected that the patient has had a relapse of disease.</p>\n<p>\n Finally, adherence to MF treatment in an outpatient setting will also be assessed. If it is proven that MF and PM combination works as well as the combination of SSG and PM, the combination of PM and MF is expected to significantly improve treatment safety and to reduce pain, while ensuring low cost and suitability to be used in remote areas.</p>\n
      • implication_results<p>\n <span style=\"font-size: 20pt; font-family: Calibri; color: rgb(86, 87, 85);\">- <span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"font-size:12px;\">Efficacy of 91.2% at 6 months follow-up in the MF/PM new treatment is </span></span></span><span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"font-size:12px;\"><span style=\"color: rgb(86, 87, 85);\">similar to</span><span style=\"color: rgb(86, 87, 85);\"> the efficacy of 91.8% in the SSG/PM arm. Non-inferiority was demonstrated in the Per Protocol analysis with </span><span style=\"color: rgb(86, 87, 85);\">92.0% efficacy in the MF/PM arm vs 91.7% in the SSG/PM arm</span></span></span></p>\n<p>\n <span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"font-size:12px;\"><span style=\"color: rgb(86, 87, 85);\">- </span><span style=\"color: rgb(86, 87, 85);\">MF/PM treatment reduces the use of SSG in </span><span style=\"color: rgb(86, 87, 85);\">Kenya. </span><span style=\"color: rgb(86, 87, 85);\">Treatment duration is reduced from 17 days to 14 days and removes one daily injection of SSG</span></span></span></p>\n
      • quantity_importedSSG 700 vial, PM 12,000-amp, MF 10136 tabs
      • quantity_dispensedSSG 331 vial, PM 7171-amp, MF 7245 tabs
      • quantity_destroyed269 Vials of Sodium Stibogluconate (SSG), 4829 amp of Paromomycin (PM) and 2891 tabs of miltefosinsin(MF)
      • quantity_exportedNA
      • balance_site0
      • final_date0000-00-00
      • modified2023-02-10 12:00:24
      • created2017-06-16 09:42:28
      • total_sites(null)
      • ecitizen_invoice(null)
      • ai_content(null)
    • InvestigatorContact(array)
      • 0(array)
        • id389
        • application_id612
        • given_nameJane
        • middle_name
        • family_nameMbui
        • qualificationMBChB, MMed (Internal Medicine), MSc Epidemiology
        • professional_addressCentre for Clinical Research Kenya Medical Research Institute
        • telephone+254 20 2722541 ext 3211 (office) +254 722 755358 (mobile)
        • emailjmbui@kemri.org
        • investigator_roleprincipal
        • created2017-06-16 10:14:04
        • modified2020-03-03 09:20:44
    • SiteDetail(array)
      • 0(array)
        • id493
        • application_id612
        • county_id30
        • site_nameKimalel Health Centre
        • physical_addressBaringo County, Marigat district, Kenya
        • contact_detailsDr. Kioko - +254710 372 352
        • contact_personDr. Kioko
        • site_capacity(null)
        • misc(null)
        • created2017-06-16 10:14:04
        • modified2020-03-03 09:20:44
        • County(array)
          • id30
          • county_nameBaringo
          • created2012-06-15 10:25:39
          • modified2012-06-15 10:25:39
      • 1(array)
        • id494
        • application_id612
        • county_id24
        • site_nameKacheliba sub-county hospital
        • physical_addressWest Pokot County, North Pokot district, Kacheliba division.
        • contact_detailsMark Riongoita - 0717478314 / 0735870606
        • contact_personMark Riongoita
        • site_capacity(null)
        • misc(null)
        • created2017-06-16 11:27:40
        • modified2020-03-03 09:20:44
        • County(array)
          • id24
          • county_nameWest Pokot
          • created2012-06-15 10:24:52
          • modified2012-06-15 10:24:52
    • Sponsor(array)
      • 0(array)
        • id313
        • application_id612
        • sponsorDrugs for Neglected Diseases Initiative
        • sponsor_typeOthers
        • contact_personGina Ouattara
        • addressTetezi Towers, 3rd Floor, George Padmore Road, Kilimani, P.O. Box, Nairobi, Kenya
        • telephone_number+254 20 3995 000
        • fax_number
        • cell_number+254790203107
        • email_addressgmouattara@dndi.org
        • created2017-06-16 10:14:04
        • modified2020-03-03 09:20:44
  • 1(array)
    • Application(array)
      • id1388
      • user_id613
      • trial_status_id6
      • abstract_of_study<p>\n Multidrug resistant TB (MDR TB) has been on the rise worldwide with WHO estimating that there were 480000 cases worldwide in the year 2015. MDR TB is of global significance due to associated high mortality rates and toxicity associated with drugs used for treatment. Therefore, there is need to prevent contacts of index cases from contracting the disease</p>\n<p>\n A5300B is a Phase III, open-label, multicenter trial with a cluster-randomized superiority design (eligible contacts in the same HH are a cluster) to compare the efficacy and safety of 26 weeks of DLM versus 26 weeks of INH for preventing confirmed or probable active TB during 96 weeks of follow-up among HIV-infected and other high-risk HHCs of adults with MDR-TB (index case).</p>\n<p>\n The study will enroll adults (≥18 years) with MDR TB and their house hold contacts. Index case is defined as patient with confirmed rifampicin and isoniazid resistance. House hold contacts are individuals who currently lives or lived in the same dwelling unit or plot of land and shares or has shared the same housekeeping arrangements as the index case and who report exposure within 90 days prior to index case starting MDR –TB treatment. The house hold contacts are children aged < 5years of age or adults, adolescents and children aged above 5 years who are LTBI positive.</p>\n<p>\n  </p>\n<p>\n Globally, a target of 5610 participants will be enrolled (1726 index cases and 3452 contacts) and each participant will remain in the study for a period of 96 weeks. Kericho site anticipates to screen 100 potential index cases to enroll 70 index cases and 280 contacts</p>\n
      • study_title<p align=\"center\">\n <strong><u>P</u></strong><strong>rotecting <u>H</u>ouseholds <u>O</u>n <u>E</u>xposure to <u>N</u>ewly Diagnosed <u>I</u>nde<u>x</u> Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB)</strong></p>\n
      • laymans_summary<p>\n <strong>Title: </strong>Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (PHOENIx MDR-TB)</p>\n<p>\n <strong>Lay title</strong>: A study comparing the safety and efficacy of two drugs for preventing confirmed or probable active TB among house hold contacts of patients with MDR-TB.</p>\n<p>\n A Phase III, open-label, multicenter trial with a cluster-randomized superiority design (eligible contacts in the same household [HH] are a cluster), to compare the efficacy and safety of 26 weeks of delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing confirmed or probable active TB during 96 weeks of follow-up among high-risk household contacts (HHCs) of adults with multidrug-resistant tuberculosis (MDR-TB). High-risk HHCs are those with HIV or non-HIV immunosuppression, latent TB infection, and young children below the age of 5 years.</p>\n<p>\n Approximately 5610 (2158 index cases and 3452 household contacts) will be enrolled into the study globally. The Kericho site anticipates to enroll up to 350 participants</p>\n
      • short_titlePHOENIx MDR-TB)
      • protocol_noECCT/24/03/06
      • version_no4.0
      • date_of_protocol30-11-2022
      • study_drugdelamanid
      • disease_conditionMDR TB
      • product_type_biologicals1
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameDelamanid
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameStandard of care Isoniazid
      • comparator_registeredyes
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressKericho.DRS@usamru-k.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr Lucy Koech
      • declaration_date113-03-2024
      • declaration_principal_investigatorDr Lucy Koech
      • declaration_date213-03-2024
      • placebo_presentNo
      • study_objectives<h3>\n To compare the efficacy of 26 weeks of DLM versus 26 weeks of INH for preventing confirmed or probable active TB during 96 weeks of follow-up.</h3>\n<p>\n  </p>\n<h3>\n To compare the safety (permanently stopping study drug due to treatment-related adverse events) of 26 weeks of DLM versus 26 weeks of INH for the treatment of presumed latent TB infection (LTBI) with MDR-TB.</h3>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n  </div>\n<div>\n Started MDR-TB treatment within the past 90 days.</div>\n<div>\n Ability and willingness of the index case to provide informed consent to access</div>\n<div>\n the HH and approach HH members for evaluation</div>\n<div>\n Men and women age ≥18 years</div>\n
      • principal_exclusion_criteria<div>\n Has previously enrolled into the A5300B/I2003B/PHOENIx trial as an index case</div>\n<div>\n or HHC, or is a member of a HH which has previously enrolled into the</div>\n<div>\n A5300B/I2003B/PHOENIx trial.</div>\n<div>\n  </div>\n
      • primary_end_points<p>\n <em>The study endpoints are detailed in the parent protocol pages 72-83.</em></p>\n
      • scope_diagnosis1
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic1
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyPhase 3
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n PhD - 1</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n MMED - 2</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n MSc - 10</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n BSc - 20</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Diploma - 50</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n CAP Certified Laboratory</p>\n
      • other_details_explanation
      • other_details_regulatory_notapproved<p>\n WRAIR and KEMRI SERU</p>\n
      • other_details_regulatory_approved<p>\n Awaiting KEMRI/SERU approval</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_durationParticipant followed up for 96 Weeks
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorISONIAZID
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_statesAfrica. ASIA, South America
      • number_of_sites2
      • multi_country_listKenya, South Africa, Malawi, Botswana, Uganda, Peru, Haiti, Vietnam and Tanzania
      • data_monitoring_committeeYes
      • total_enrolment_per_site350
      • total_participants_worldwide5610
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornYes
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Fredrick Sawe
      • investigator1_middle_name
      • investigator1_family_nameSAWE
      • investigator1_qualification MBChB, MMED
      • investigator1_professional_addressKenya Medical Research Institute/Walter Reed Project P.O Box 1357 – 20200,
      • investigator1_telephone+254 703247902
      • investigator1_emailFredrick.sawe@usamru-k.org
      • organisations_transferred_No
      • number_participants350
      • notification
      • approval_date21-05-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted17-05-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted07-05-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed and approved by two (2) reviewers.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2026-04-01 09:47:30
      • created2024-03-13 08:59:16
      • total_sites(null)
      • ecitizen_invoice(null)
      • ai_content(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1048
        • application_id1388
        • given_nameDr Lucy Chepkurui Koech
        • middle_name
        • family_nameKOECH
        • qualificationMBChB
        • professional_addressKenya Medical Research Institute/Walter Reed Project P.O Box 1357 – 20200,
        • telephone+254 719193275
        • emailLucy.koech@usamru-k.org
        • investigator_roleprincipal
        • created2024-03-13 10:10:19
        • modified2024-05-17 12:46:39
    • SiteDetail(array)
      • 0(array)
        • id1684
        • application_id1388
        • county_id35
        • site_nameKenya medical Research Institute/ Walter Reed Project
        • physical_addressOFF Hospital Road
        • contact_detailsP.O. BOX 1357 Kericho
        • contact_personDr Lucy C. Koech
        • site_capacity(null)
        • misc(null)
        • created2024-03-13 10:10:19
        • modified2024-05-17 12:46:39
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
      • 1(array)
        • id1712
        • application_id1388
        • county_id27
        • site_nameMoi university clinic research Centre
        • physical_addressAmpath Centre at MTRH
        • contact_detailsP.O.BOX 4604 Eldoret
        • contact_personDr Abraham Mosigisi Siika
        • site_capacity(null)
        • misc(null)
        • created2024-05-17 11:11:31
        • modified2024-05-17 12:46:39
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
    • Sponsor(array)
      • 0(array)
        • id732
        • application_id1388
        • sponsorNational Institute of Allergy and Infectious Diseases National Institute of Child Health and Human Development
        • sponsor_typeResearch Institution
        • contact_person
        • addressACTGIMPAACT.COREPHOENIX@fstrf.org
        • telephone_number301-897-1707.
        • fax_number
        • cell_number301-897-1707.
        • email_addressACTGIMPAACT.COREPHOENIX@fstrf.org
        • created2024-03-13 10:10:19
        • modified2024-05-17 12:46:39
  • 2(array)
    • Application(array)
      • id1127
      • user_id263
      • trial_status_id5
      • abstract_of_study<p>\n Sickle cell disease (SCD) is a related group of common and rare hemoglobin (Hb) genotypes in which all affected individuals are either homozygotes for the sickle Hb (HbS) mutation of the β-globin subunit or compound heterozygotes for HbS and another globin gene mutation. A hallmark symptom of SCD is a painful Vaso-occlusive crisis (VOC). An interplay of the various pathologic processes in SCD perpetuates and feeds forward an inflammatory priming that, in the presence of a precipitating event, can lead to a VOC. VOCs are responsible for a wide variety of clinical complications of SCD, including pain syndromes, acute chest syndrome (ACS), stroke, priapism, leg ulcers, spontaneous abortion, renal insufficiency, and multiorgan failure leading to death. Frequency of VOCs, along with Absolute Neutrophil count (ACS), is the most common predictor of death in patients with SCD. Thus, early identification, treatment, and prevention of VOCs could significantly impact the natural course of the disease. Interventions for treatment and prevention of longer-term complications are urgently needed.</p>\n<p>\n  </p>\n<p>\n About 240,000 children in Africa, are born each year with Sickle Cell Disease (SCD), while here in Kenya, it is estimated that 6,000 children are born with the disease. Sadly, between 50 to 80 per cent of these children die before their fifth birthday. The recurrent pain and complications caused by the disease, can interfere with many aspects of the patient’s life, including education, employment and psychosocial development.</p>\n
      • study_title<p align=\"center\">\n <strong>A Phase 2a Randomized, Double-Blind, Placebo-Controlled Study to Characterize the Pharmacokinetics and Pharmacodynamics of Rifaximin Novel Formulations in Patients with Sickle Cell Disease</strong></p>\n
      • laymans_summary<p>\n The objective of this study is to understand/characterize the pharmacokinetic/PK (how our bodies affect the drug) and the Pharmacodynamics/PD (meaning how the drug affects our bodies) of a drug called Rifaximin, which is used in treatment of patients with sickle cell disease.</p>\n<p>\n Of the current treatment options available for sickle cell disease, only bone marrow transplant is a permanent cure, but few patients qualify for this treatment. Patients on the other treatment options e.g., hydroxyurea and L glutamine may still experience acute clogging of blood vessels called Vaso Occlusive crisis (VOC) There is a need to find more treatment options for sickle cell disease that prevents the VOC.</p>\n
      • short_titleSickle Cell Disease
      • protocol_noECCT/22/03/06
      • version_noVersion 2.0_16 Aug 2021
      • date_of_protocol16-08-2021
      • study_drugrifaximin ER and DER
      • disease_conditionSickle cell disease
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_namexifaxan
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMichelle Botha
      • declaration_date120-03-2022
      • declaration_principal_investigatorDr L Tina
      • declaration_date220-03-2022
      • placebo_presentYes
      • study_objectives<p>\n The objectives of this study are: To characterize the pharmacokinetics/pharmacodynamics (PK/PD) of rifaximin ER and DER in subjects with sickle cell disease (SCD) and to assess the safety and tolerability of rifaximin (Extended Release) ER and Delayed Extended Release (DER).</p>\n
      • principal_inclusion_criteria<p>\n Participants are eligible for the study only if all the following criteria are met:</p>\n<ol>\n <li>\n Subject must have the ability and willingness to sign a written informed consent form.</li>\n <li>\n Subject is between the ages of 18 to 70 years old (inclusive) at the time of consent.</li>\n <li>\n Subject has SCD of any genotype (HbSS, HbSC, HbS β-thalassemia). If the subject’s genotype has not been previously documented, genotyping will be performed during Screening using high-performance liquid chromatography (HPLC)/electrophoresis.</li>\n <li value=\"4\">\n Subject must have experienced at least 2 VOCs within the 12 months prior to Screening. A VOC is defined as: </li>\n</ol>\n<p>\n                             a. The occurrence of appropriate symptoms consistent with a painful crisis, acute chest syndrome (ACS), or priapism, and</p>\n<p style=\"margin-left: 72pt;\">\n b. Requires a visit to a medical facility and/or healthcare professional, and</p>\n<p style=\"margin-left: 72pt;\">\n c. Receipt of either a parenteral or oral opioid or NSAID analgesia.</p>\n<ol>\n <li value=\"5\">\n If subject is receiving hydroxyurea (HU)/hydroxycarbamide (HC), subject must have been receiving the treatment for at least 6 months prior to Screening and must agree to maintain the same dose and schedule for the duration of the study.</li>\n <li value=\"6\">\n Subjects must have laboratory values at Screening within the following ranges:\n <ul>\n <li>\n Absolute Neutrophil Count ≥1.0 x 109/L</li>\n <li>\n Platelets ≥ 75 x 109/L</li>\n <li>\n Hemoglobin (Hgb) ≥ 6.0 g/dL</li>\n <li>\n Glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2 using the CKD-EPI formula</li>\n <li>\n Direct (conjugated) bilirubin ≤ 2.0 x ULN</li>\n <li>\n Alanine transaminase (ALT) ≤ 3.0 x ULN</li>\n <li>\n International Normalized Ratio (INR) ≤ 2.0</li>\n </ul>\n </li>\n <li value=\"7\">\n Eastern Cooperate Oncology Group (ECOG) performance status ≤ 2.</li>\n <li value=\"8\">\n Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test at Screening and agree to use standard prevention methods for the duration of the study.</li>\n</ol>\n
      • principal_exclusion_criteria<p>\n Participants are not eligible for inclusion for the trial if any of the following criteria are met:</p>\n<ol>\n <li>\n Subject is receiving concomitant treatment with voxelotor, crizanlizumab, or L-glutamine.</li>\n <li>\n Subject has any history of stem cell transplant is planning to begin or has received in the past 30 days.</li>\n <li value=\"3\">\n Subject experiences an acute VOC, requiring a visit to a medical facility and/or healthcare professional, ending within 7 days prior to Day 1 dosing.</li>\n <li value=\"4\">\n Subject has received any blood products within 30 days of Day 1 dosing.</li>\n <li value=\"5\">\n Subject has uncontrolled liver disease or renal impairment, ulcerative colitis, Crohn’s disease, or other chronic GI disorder.</li>\n <li value=\"6\">\n Subject has received active treatment in another investigational trial within 30 days or 5 half-lives of the last dose of the investigational agent, whichever is greater, prior to Screening.</li>\n <li value=\"7\">\n Subject has received penicillin prophylaxis or antibiotics for treatment of infection within 30 days or 5 half-lives of the treatment, whichever is greater, prior to Screening.</li>\n <li value=\"8\">\n Subject has a significant medical condition that required hospitalization (other than for a VOC) within 2 months prior to Screening.</li>\n <li value=\"9\">\n Subject is planning on undergoing an exchange transfusion during the duration of the study or has completed one within 4 weeks prior to Day 1 dosing.</li>\n <li value=\"10\">\n Subject has a hypersensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any components of rifaximin ER and DER.</li>\n <li value=\"11\">\n Subject has used therapeutic anticoagulation (prophylactic doses are permitted) or antiplatelet therapy (other than aspirin or NSAIDs) within 10 days prior to Day 1 dosing.</li>\n <li value=\"12\">\n Subject is pregnant or a nursing woman.</li>\n <li value=\"13\">\n Subject has a history of illicit drug use or abuse, either documented or in the opinion of the Investigator.</li>\n <li value=\"14\">\n Subject is using any medication that is known to inhibit or induce CYP3A4, P-gp, or OATP1B1/B3 (See Appendix 3) within 30 days or 5 half-lives, whichever is longer, prior to Day 1 dosing, or in the opinion of the Investigator, may affect the evaluation of the study product or place the subject at undue risk.</li>\n <li value=\"15\">\n Subject has had any prior gastrointestinal surgery which has altered the anatomy of the esophagus, stomach, or small/large intestine (with the exception of appendectomy, cholecystectomy, and fundoplication).</li>\n <li value=\"16\">\n Subject has had a colonoscopy or sigmoidoscopy within 30 days prior to Day 1 or plans to undergo such a procedure during the duration of the study.</li>\n <li value=\"17\">\n Subject has used bowel prep, laxative, or enema within 30 days prior to Day 1.</li>\n <li value=\"18\">\n Subject has a bleeding disorder including, but not limited to, acquired or congenital platelet function defects, disseminated intravascular coagulation (DIC), bleeding factor deficiencies, hemophilia, idiopathic thrombocytopenia purpura (ITP), or von Willebrand’s disease.</li>\n <li value=\"19\">\n Subject is planning to undergo a major surgical procedure during the duration of the study.</li>\n <li value=\"20\">\n Subject has a positive test for human immunodeficiency virus (HIV)1 or HIV2.</li>\n <li value=\"21\">\n Subject has an active Hepatitis B infection (HBsAg positive). Prior infection that is not active (i.e., HBsAg negative, HBcAb positive, and HBsAb positive) is permitted.</li>\n <li value=\"22\">\n Subject has a positive test for Hepatitis C (HCV RNA). Prior infection with spontaneous resolution or sustained resolution for ≥ 24 weeks after cessation of antivirals is permitted.</li>\n <li value=\"23\">\n Subject has an active COVID-19 infection or complication(s) related to COVID-19 infection that are unresolved or, in the opinion of the Investigator, may affect evaluation of the study drug or place the subject at undue risk.</li>\n <li value=\"24\">\n Subjects has received a vaccine (including COVID-19 vaccine) within 2 weeks prior to Screening. If subject has received their first of two COVID-19 vaccination doses, as applicable, they must wait for at least 2 weeks after receiving the second dose, and be symptom-free, prior to beginning Screening. Subject must not be planning for COVID-19 or other vaccinations while on study.</li>\n <li value=\"25\">\n Subject has a malignant disease. Exceptions include malignancies that were treated curatively and have not recurred within 2 years prior to study treatment, completely resected basal cell and squamous cell skin cancers, and any completely resected carcinoma in situ.</li>\n <li value=\"26\">\n Subjects has prolonged QT interval as assessed by ECG history within the past 3 months. For subjects with no historical ECG information, subject has a resting QTcF ≥ 460 msec for males and ≥ 470 msec for females at Screening.</li>\n <li value=\"27\">\n Subject has any unstable cardiac condition that, in the opinion of the Investigator, may worsen during the study or interfere with successful evaluation of the study treatment.</li>\n <li value=\"28\">\n Subject has a serious mental or physical illness which, in the opinion of the Investigator, would compromise participation in the study.</li>\n <li value=\"29\">\n Subject has any condition which, in the opinion of the Investigator, is likely to interfere with the successful collection of the measurements required for the study.</li>\n</ol>\n
      • primary_end_points<p>\n Full rifaximin and 25-desacetyl rifaximin plasma PK profiles following administration on Days 1 and 29 and C_max and C_trough on Days 8, 15, and 29 will be evaluated at specified timepoints according to the schedule of activities.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n 1. Victoria Biomedical Research Institute (VIBRI) (PI:  LO Tina):</p>\n<p>\n VIBRI is a non-profit providing pharmaceutical, academic research and non-profit organization with a network of clinical sites and expertise focusing on accelerating transformative therapeutics, vaccines, and devices research for major gloabl health diseases in Kenya.  VIBRI is located at the Kisumu County Referral Hospital in Kisumu County, western Kenya.  VIBRI was established to conduct biomedical research including clinical trials, bioequivalence studies, basic science research studies, epidemiology and population health studies, implementation science studies, build a strong doundation in data science, conduct training and capacity building on clinical research in Kenya.  VIBRI has experienced and accomplished clinical research scientists who have designed and conducted GCP compliance phase 1b to phase IV paediatric and adult clinical trials.  </p>\n<p>\n 2. CREATES (PI:  Dr Bernhards Ogutu):</p>\n<p>\n The KUTRH is designed for clinical trials with a bed space of 600 and ICU beds of 25.  It is a referral healthcare facility experienced in clinical trials. The PI is support by a large team of experienced Sub Investigators and SSCs.  Along with experienced pharmacists to manage the IP.  The site has ample well-equipped clinical laboratories, radiological services and ample clinical observation areas as well as spacious research operations office.</p>\n<p>\n 3. International Cancer Institute (PI:  Prof. FC Asirwa):</p>\n<p align=\"left\" style=\"margin-left:.45pt;\">\n The study will be conducted at the International Cancer Institute (ICI) in Eldoret, Kenya. Recruitment will occur at the research and care clinic located along Nandi Road. ICI research and care clinic is staffed by qualified research personnel including 1 Medical Oncologist, 1 Clinical Oncologist, 4 medical officers, 1 Pharmacist, 1 pharmaceutical Technologist, 1 clinical officer, 4 nurses,1 consultant pathologist, 2 laboratory technologists, 1 patient navigator and 1 administrator. ICI has a research and molecular diagnostics laboratory, for sample testing and storage. The site has a registration area, consultation rooms, examination rooms, chemotherapy administration area, records and data storage, pharmacy and laboratory. International Cancer Institute currently runs a clinic where patients with SCD from Uasin Gishu County and different parts of the Country are managed. The site participates in several other Randomized controlled trials with key focus on Haemato-oncology trials.</p>\n<p>\n 4. KEMRI/USAMRD-K Kombewa Clinical Research Center (PI: Janet Oyieko)</p>\n<div>\n The KEMRI/WRP Kombewa Clinical Research Center (KCRC) is designed for large clinical</div>\n<div>\n trials and has a full clinical laboratory including microbiology capability.</div>\n<div>\n KCRC is part of The Walter Reed Project (WRP), which is a 40-year collaboration between the</div>\n<div>\n Kenya Medical Research Institute, (KEMRI) and the Walter Reed Army Institute of Research</div>\n<div>\n (WRAIR). The US Army Medical Research Unit in Kenya (USAMRU-K) is a WRAIR</div>\n<div>\n attachment stationed in Kenya with headquarters in Nairobi and field stations in Kericho and</div>\n<div>\n Kisumu. WRP-Kisumu conducts a wide spectrum of field and laboratory work including</div>\n<div>\n numerous clinical research trials.</div>\n
      • other_details_explanation<p>\n Study is being conducted in America</p>\n
      • other_details_regulatory_notapproved<p>\n Applications are planned for Egypt and Lebanon</p>\n
      • other_details_regulatory_approved<p>\n US FDA provided approval to proceed on 11 June 2021</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration6 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites4
      • multi_country_listNorth America\nMiddle east
      • data_monitoring_committeeNo
      • total_enrolment_per_site3-10
      • total_participants_worldwide60
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameLucas
      • investigator1_middle_nameOtieno
      • investigator1_family_nameTina
      • investigator1_qualificationMBChB, MSc, DLSHTM
      • investigator1_professional_addressVictoria Biomedical Research Institute
      • investigator1_telephone+254720596654
      • investigator1_emaillucas.tina0818@gamil.com
      • organisations_transferred_Yes
      • number_participants20
      • notification
      • approval_date15-09-2022
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted09-05-2022
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer comments have been addressed
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-06-11 12:33:58
      • created2022-03-09 10:16:30
      • total_sites(null)
      • ecitizen_invoice(null)
      • ai_content(null)
    • InvestigatorContact(array)
      • 0(array)
        • id799
        • application_id1127
        • given_nameJanet
        • middle_name
        • family_nameOyieko
        • qualificationMBChB, MMED, PhD
        • professional_addressKombewa Clinical Research Centre
        • telephone+254721996988
        • emailjanet.oyieko@gmail.com
        • investigator_roleprincipal
        • created2022-03-09 11:01:56
        • modified2022-05-09 16:38:41
      • 1(array)
        • id800
        • application_id1127
        • given_nameFredrick
        • middle_nameChite
        • family_nameAsirwa
        • qualificationProf, M.D.
        • professional_addressInternational Cancer Institute (ICI).
        • telephone+254 718 473 446
        • emaildirector@intercancer.com
        • investigator_roleprincipal
        • created2022-03-11 10:09:31
        • modified2022-05-09 16:38:41
      • 2(array)
        • id801
        • application_id1127
        • given_nameBernhards
        • middle_name
        • family_nameOgutu
        • qualificationMBChB, MSc
        • professional_addressCREATES - Strathmore University Medical Centre
        • telephone+254733812613
        • emailogutu6@gmail.com
        • investigator_roleprincipal
        • created2022-03-11 10:09:31
        • modified2022-05-09 16:38:41
    • SiteDetail(array)
      • 0(array)
        • id1253
        • application_id1127
        • county_id42
        • site_nameKombewa Clinical Research Centre
        • physical_addressOff Kisumu-Bondo Road, opposite Kombewa county Hospital
        • contact_details+254721996988
        • contact_personDr. Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2022-03-09 11:01:56
        • modified2022-05-09 16:38:41
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1254
        • application_id1127
        • county_id42
        • site_nameVictoria Biomedical Research institute
        • physical_addressP.O BOX 7180-40100 KISUMU
        • contact_details+254720597654
        • contact_personDr. Lucas Otieno tina
        • site_capacity(null)
        • misc(null)
        • created2022-03-11 09:22:47
        • modified2022-05-09 16:38:41
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1255
        • application_id1127
        • county_id27
        • site_nameInternational Cancer Centre
        • physical_addressNandi road, P.O BOX 8088, Eldoret
        • contact_details+254700522149
        • contact_personDr. Fredrick Asirwa
        • site_capacity(null)
        • misc(null)
        • created2022-03-11 09:22:47
        • modified2022-05-09 16:38:41
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 3(array)
        • id1256
        • application_id1127
        • county_id47
        • site_nameCREATES - Strathmore University Medical Centre
        • physical_addressP.O BOX 59857 - 00200 Madaraka Estate, Nairobi
        • contact_details+254733812613
        • contact_personDr. Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2022-03-11 09:22:47
        • modified2022-05-09 16:38:41
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id583
        • application_id1127
        • sponsorSalix Pharmaceuticals, Inc., a division of Bausch Health US, LLC.
        • sponsor_typeIndustry
        • contact_person
        • addressBausch Health US, LLC Bridgewater, NJ 08807 USA
        • telephone_number1-800-321-4576
        • fax_number
        • cell_number 908-927-1400
        • email_addressSean.Humphrey@bauschhealth.com
        • created2022-03-09 11:01:56
        • modified2022-05-09 16:38:41
  • 3(array)
    • Application(array)
      • id1585
      • user_id1008
      • trial_status_id(null)
      • abstract_of_study<p>\n The burden of HIV-1 infection remains disproportionately high among adolescent girls and young women in sub-Saharan Africa, including Kenya. While daily oral pre-exposure prophylaxis (PrEP) has demonstrated effectiveness in preventing HIV acquisition, adherence to daily dosing remains a significant barrier to optimal use. MK-8527 is a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) developed by Merck Sharp & Dohme (MSD) for once-monthly oral PrEP. Due to its high potency and long half-life, MK-8527 has the potential to reduce the risk of HIV acquisition without relying on adherence to a daily regimen</p>\n<p>\n This study is a Phase III randomized, double-blind, active-controlled, multicentre clinical trial (protocol MK-8527-010-00) designed to assess the efficacy, safety, and tolerability of MK-8527 administered once monthly compared to the standard daily oral FTC/TDF regimen. The primary objective of this study is to evaluate the efficacy, safety, and tolerability of MK-8527 monthly compared to FTC/TDF daily for the prevention of HIV-1 infection as assessed by the incidence rate per year of adjudicated HIV-1 infections and the number of adverse events reported leading to discontinuation of study intervention. The study will enrol approximately 4,580 HIV-negative cisgender women (<strong>assigned female at birth and who identify as women)</strong> aged 16 to 30 years who are at increased risk of HIV-1 acquisition, defined as those with behavioral, biological, or partner-based risk factors (e.g., history of STIs, condomless sex with multiple or HIV-positive partners). Participants will be randomized in a 1:1 ratio to receive either MK-8527 (11 mg monthly) or FTC/TDF (200 mg/245 mg daily), with matched placebo to preserve blinding. Study interventions will be administered for up to 24 months, followed by a 28-day open-label follow-up period.</p>\n<p>\n At the Rachuonyo Clinical Research Site located within Rachuonyo South County Hospital in Homa Bay County, Kenya, at least 200 participants will be enrolled. The site was selected due to its experienced research infrastructure, high HIV burden in the catchment population, and strong community engagement mechanisms. Participants will attend monthly visits for HIV testing, medication dispensation, adherence assessments, safety evaluations, and pharmacokinetic sampling. Participants who become pregnant may continue in the study on open-label daily FTC/TDF, with optional infant follow-up to 1 year of age to assess safety, growth, and potential HIV transmission.</p>\n
      • study_title<p align=\"center\">\n <strong>A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to </strong><strong>Evaluate the Efficacy and Safety of MK-8527 Oral Once-Monthly as HIV-1 Preexposure Prophylaxis in Women</strong></p>\n
      • laymans_summary<p>\n HIV is still a serious health problem in many parts of Africa, especially for teenage girls and young women. In Kenya, more than 1.4 million people are living with HIV. Girls and young women between the ages of 16 and 30 are more likely to get infected with HIV than others, mainly because of things like limited access to protection, social pressure, and unequal relationships. Although there are medicines that can help prevent HIV, like the daily PrEP pill, many people find it hard to take a pill every day. A long-acting, PrEP option given as an injection called Cabotegravir, every 2 months, was approved by the United States of America Food and Drug Administration (US FDA) in 2021 and added to WHO recommendations in July 2022. Cabotegravir for PrEP is currently approved in many countries worldwide. While cabotegravir was shown to prevent HIV-1 more than daily oral PrEP in clinical studies, it is not readily available in many countries. To help with this, a company called Merck Sharp & Dohme (MSD) has developed a new HIV prevention pill called MK-8527, which only needs to be taken once a month<strong>.</strong> This study is being done to find out if MK-8527 is safe and works well in preventing HIV, compared to the daily PrEP pill called FTC/TDF (Truvada), which is currently in use.</p>\n<p>\n The study, named MK-8527-010-00<strong>,</strong> is being done in Kenya, Uganda, and South Africa. It includes women between the ages of 16 and 30 who are more likely to get infected with HIV, especially those with multiple partners, not using condoms regularly, or having had a sexually transmitted infection. The women in the study will be placed into two groups by chance: one will take the new monthly pill (MK-8527), and the other will take the regular daily PrEP pill. Neither the participants nor the doctors will know which pill each person is taking until the study is over — this is called a double-blind study to make the results more accurate. Across all countries, about 4,580 women will join the study. In Kenya, the Rachuonyo Clinical Research Site<strong>,</strong> located at Rachuonyo South County Hospital in Homa Bay County, will enroll at least 200 women. Participants will visit the clinic once a month for up to two years to receive their medication, get tested for HIV, and have their health checked.</p>\n<p>\n If a participant becomes pregnant during the study, she can choose to continue in the study with the currently approved medication (daily PrEP) after discussing the benefits and risks with the study team. With her permission, her baby may also be checked and followed for up to a year to make sure everything is okay.</p>\n<p>\n The study will also check how easy it is for participants to take the pill, how they feel about it, and how the drug works in their body. If anyone gets HIV during the study, more tests will be done to understand how and why that happened.</p>\n<p>\n The results of this study could offer a new, easier-to-use option for HIV prevention<strong>,</strong> especially for young women who have trouble taking a pill every day. If the monthly pill works well, it could help reduce new HIV infections in Kenya and in other parts of the world.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • short_titleMK-8527-010
      • protocol_noECCT/25/08/06
      • version_noProtocol version 010-00
      • date_of_protocol25-04-2025
      • study_drugMK8527
      • disease_conditionHIV prevention
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameAn International Nonproprietary Name or INN
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameDaily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
      • comparator_registeredYes by FDA Approval 02/08/2004
      • comparator_countriesThe comparator drug FTC/TDF (Truvada) is registered in the United States, European Union, China, South Africa, Nigeria, and in numerous additional countries through WHO-prequalified generics distributed globally.
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressiinwani@yahoo.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicant+254 722 608 483
      • declaration_date121-08-2025
      • declaration_principal_investigator+254 733617503
      • declaration_date221-08-2025
      • placebo_presentYes
      • study_objectives<p>\n  The primary objective of this study is to evaluate the efficacy, safety, and tolerability of MK-8527 monthly compared to FTC/TDF daily for the prevention of HIV-1 infection as assessed by the incidence rate per year of adjudicated HIV-1 infections and the number of adverse events reported leading to discontinuation of study intervention.</p>\n
      • principal_inclusion_criteria<p>\n  Inclusion Criteria An individual is eligible for inclusion in the study if the individual meets all of the following criteria: Type of Participant and Disease Characteristics 1. Is confirmed HIV-uninfected based on negative HIV-1/HIV-2 test results during screening. Note: Any positive HIV test during the Screening Period will exclude the participant from the study regardless of a negative confirmatory test. Additional testing to confirm suspected HIV infection during screening will be performed in accordance with local guidelines. If HIV infection is confirmed, participants will be referred for appropriate care, as necessary.</p>\n<p>\n 2. Has been sexually active (2 vaginal intercourse encounters with cisgender male individual(s) within the last 3 months).</p>\n<p>\n Demographics</p>\n<p>\n 3. Was assigned female sex at birth, and is cisgender.</p>\n<p>\n 4. Aged from 16 years to 30 years of age inclusive, at the time of providing the informed consent or assent, as applicable. Note: Enrollment for 16- to 17-year-old participants may begin only after completion and review of the initial safety review results by the eDMC (refer to the section on statistical considerations).</p>\n<p>\n 5. Weighs 35 kg at enrollment. Assigned Female Sex at Birth</p>\n<p>\n 6. A participant assigned female sex at birth is eligible to participate if not breast/chestfeeding. 0</p>\n<p>\n 7. A POCBP is eligible to participate if not pregnant and if a negative highly sensitive pregnancy test (urine or serum), as required by local regulations, has been obtained within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.5. The definition of childbearing potential is in Appendix 5.</p>\n<p>\n Informed Consent 8. The participant (or participant’s legally acceptable representative) has provided documented informed consent and the participant has provided documented assent, when applicable, for the study. Additional Categories</p>\n<p>\n 9. Has no plans to travel or relocate away from the site that would interfere with attending monthly on-site visits for the duration of the study. The following criteria must also be met to enroll in the Contraceptive Implant Injection DDI Substudy:</p>\n<p>\n 10. Is currently using an ENG-releasing implant (ie, Nexplanon or Implanon NXT) or injectable-MPA or injectable-NET-EN or is willing to begin use at the Screening Visit. (Section 8.6.4).</p>\n
      • principal_exclusion_criteria<p>\n Exclusion Criteria</p>\n<p>\n An individual must be excluded from the study if the individual meets any of the following criteria: Medical Conditions</p>\n<p>\n 1. Has hypersensitivity or other contraindication to any component of the study interventions as determined by the investigator.</p>\n<p>\n 2. Has evidence of acute or chronic hepatitis B infection (HBsAg positive). Note: Participants with isolated HBcAb positivity (HBsAg and HBsAb negative) will be excluded if HBV DNA is positive. Note: Participants who do not demonstrate immunity to HBV will be offered HBV vaccination.</p>\n<p>\n 3. Has a history of malignancy within 5 years of screening except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.</p>\n<p>\n 4. Has a history or current evidence of any condition (eg, active tuberculosis infection or hepatic cirrhosis), therapy, laboratory abnormality or other circumstance (including substance or alcohol use disorder) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to enroll. Prior/Concomitant Therapy</p>\n<p>\n 5. Has taken cabotegravir, lenacapavir, or any other long-acting HIV prevention product at any time (past or current use). Note: Prior use of ISL (MK-8591) is permitted.</p>\n<p>\n 6. Is currently receiving or is anticipated to require any prohibited therapies outlined in Section 6.5 from 30 days prior to Day 1 through the study duration (ie, up to 56 ±5 days following the last dose of blinded monthly study intervention). Note: Participants taking or starting tenofovir-based PrEP at screening may continue their regimen until 24 hours before the blinded monthly dose on Day 1. Dapivirine ring can be removed on Day 1 prior to administration of study intervention.</p>\n<p>\n 7. Has received an HIV vaccine at any time (ie, through past participation in an investigational clinical study) or monoclonal antibodies to HIV within 12 months before Day 1. Prior/Concurrent Clinical Study Experience</p>\n<p>\n 8. Is currently participating in or has participated in an interventional or prevention clinical study with an investigational compound or device within 30 days prior to Day 1 through the duration of the study. Note: Concurrent participation in observational or noninterventional studies or longitudinal follow-up from interventional studies may be permitted and should be discussed with the Sponsor before enrollment and through study duration.</p>\n<p>\n Diagnostic Assessments</p>\n<p>\n 9. Has exclusionary laboratory values within 45 days prior to Day 1 as listed in Table 1. Note: A single repeat of a laboratory screening test will be allowed for test results that are unexpected, but the repeat test results must be available within the 45-day screening window.</p>\n<p>\n Laboratory Exclusion Criteria:</p>\n<p>\n Table 1 Laboratory Assessment ExclusionaryValues</p>\n<p>\n A<strong>bsolute neutrophil count</strong> ≤750 cells/mm3</p>\n<p>\n <strong>Alkaline phosphatase</strong> >3 × ULN ALT >3 × ULN AST >3 × ULN</p>\n<p>\n <strong>Total bilirubin </strong>≥2.5 × ULN eGFR <60 mL/min/1.73 m2</p>\n<p>\n <strong>Hemoglobin </strong><9.0 g/dL</p>\n<p>\n <strong>Platelet coun</strong>t <100,000/mm3</p>\n<p>\n ALT=alanine aminotransferase; AST=aspartate aminotransferase; eGFR=estimated glomerular filtration rate; ULN=upper limit of normal.</p>\n<p>\n  Other Exclusions</p>\n<p>\n 10. Is expecting to donate eggs at any time during the study. Note: Investigators should provide appropriate guidance to participants regarding egg donation after completion of the study intervention. It is recommended that all participants refrain from egg donation for at least 56 days following their last dose of blinded monthly study intervention.</p>\n<p>\n 11. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.</p>\n
      • primary_end_points<p>\n 1. Adjudicated HIV-1 infection</p>\n<p>\n 2.  -Adverse events-Adverse events leading to discontinuation of study intervention</p>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>Irene Inwani, MD, MMed, MPH</strong></p>\n<p>\n Site Principal Investigator (PI) at Rachuonyo. Oversees all activities at the site including study design, data collection, intervention implementation, and overall administrative management. Coordinates closely with the central team to ensure adherence to protocol and smooth study execution<strong>.</strong></p>\n<p>\n <strong>Carey Farquhar, MD, MPH</strong></p>\n<p>\n Co-Principal Investigator. Provides high-level oversight of all research components including design and implementation of interventions, data management, and fiscal aspects. Supports collaboration between UW and Kenyan partners.</p>\n<p>\n <strong>John Kinuthia, MBChB, MMed, MPH</strong></p>\n<p>\n Responsible for engaging stakeholders and regulatory bodies. Supports regulatory documentation and assists with communication across various implementing partners.</p>\n<p>\n <strong>Marilyn Nyabuti, MBChB, MPH</strong></p>\n<p>\n Leads development and operationalization of participant recruitment and retention strategies. Works closely with the community engagement and field team to maximize retention rates.</p>\n<p>\n <strong>Elizabeth Irungu, MBChB, MPH, PhD</strong></p>\n<p>\n Provides technical support to site clinicians implementing the clinical trial. Advises and mentors the study coordinator and data management team to ensure technical and quality standards are met.</p>\n<p>\n <strong>Nancy Ngumbau, MBChB, MPH</strong></p>\n<p>\n Handles compliance with ethical and regulatory requirements. Ensures that human subject protections are upheld throughout the research process.</p>\n<p>\n <strong>Stanley Ndwiga, MBChB, MPH</strong></p>\n<p>\n Dr. Ndwiga is a medical doctor with a MPH from the University of Washington. Dr. Ndwiga has extensive experience conducting clinical trials and research studies and will be on-site in western Kenya to oversee trial activities at Rachuonyo.  He is responsible for the smooth functioning of the research project, coordinating communications with regulatory boards, staff, and investigators, and assisting investigators with implementation, planning, and problem-solving to ensure project goals are met. He will be the go-to person at the site for consultation and communicate regularly with team members based in Nairobi and Seattle.</p>\n<p>\n <strong>Bhavna Chohan, PhD</strong></p>\n<p>\n Laboratory Director providing regulatory oversight, ensuring lab equipment is compliant and SOPs are followed. Supports local lab team and ensures lab standards align with global trial requirements.</p>\n<p>\n  </p>\n<p>\n <strong>Program Manager</strong></p>\n<p>\n Based at University of Washington overseeing financial and administrative management for the trial. Provides liaison support between UW and Kenyan collaborators.</p>\n<p>\n <strong>Project Administrator (1), Site Admin Assistant (1)</strong></p>\n<p>\n The administrators will be responsible for assisting in overall planning for the project in liaison with the coordinator, PI, and the program manager, and assist in budget preparation, maintaining of proper audit trail for study funds and expenditures, generating monthly invoices, and other financial reports as required in the subcontract. He/she will also be responsible for handling and accounting for the field advance given to the project. Will also oversee site administrative and financial activities with the help of. She/he is responsible for the recruitment of personnel and all staff-related issues such as disciplinary, medical insurance, salaries, and remuneration, among others.  Site admin assistant will provide administrative and operational support. Assists in training logistics, procurement, and coordination of communication.</p>\n<p>\n <strong>Recruitment, Retention & Community Engagement Lead (1)</strong></p>\n<p>\n Will design and lead implementation of community engagement and participant retention strategies. Participates in stakeholder meetings and international engagements to enhance recruitment effectiveness. Coordinates hospital administration and community engagement. Organizes meetings and advises on participant mobilization and retention strategies</p>\n<p>\n <strong>Pharmacist (2) and pharmaceutical technologist (1)</strong></p>\n<p>\n The pharmacist of record will be assisted by one pharmacist and one pharmaceutical technologist. Pharmacist of record is responsible for study drug management, regulatory compliance with PPB, dispensing, adherence support, and drug accountability. They will assist in dispensing drugs and provide adherence counseling. They will also be responsible for tracking the amount of study drug kits and ensuring documentation of the same.</p>\n<p>\n <strong>Recruitment and Retention Officers (4) </strong></p>\n<p>\n Develop and execute strategies for recruiting and retaining study participants. Assist with community outreach and follow-up.</p>\n<p>\n <strong>Study Doctor (2)</strong></p>\n<p>\n Implements study clinical procedures, reviews eligibility and manages participant care. The study doctor responsible as physician for the study participants, their review and safety and Adverse event (AE) monitoring, and safety reporting to the PI, study safety monitor, sponsor, and regulatory review bodies.</p>\n<p>\n <strong>Study Nurses (2 )</strong></p>\n<p>\n Provide nursing care including evaluation, monitoring, and support to participants during the study.</p>\n<p>\n <strong>Quality Assurance Officer (1)</strong></p>\n<p>\n Monitors compliance with study protocols and GCP. Conducts quality checks and works closely with the study coordinator to uphold high standards.</p>\n<p>\n <strong>Lab Manager (1), Lab Technologists (1)</strong></p>\n<p>\n The Laboratory Manager will be responsible for the overall management of the laboratory, authoring the laboratory SOPs, ensuring that all equipment is serviced and calibrated, and ensuring that all tests are done as per the study protocol. The laboratory technologists will be responsible for performing all the lab tests required for the participants, maintaining and charting the temperature logs in the laboratory, preparing samples for archiving and shipment, and ensuring proper storage is done. They will also maintain the Study documents in files and folders, appropriately monitor any abnormal results for participants, and notify the clinicians appropriately.</p>\n<p>\n <strong>Data manager (1), data quality assurance officer (1), and data clerks (2)</strong></p>\n<p>\n The data manager will be responsible for the overall management of the study data, ensuring all the needed databases are created and reports generated on a timely basis as needed for each database. Ensuring the confidentiality of participants' data by creating a link log between the participants' study ID and participants' names, which will be kept separately under double-locked cabinets. The data quality officer will be responsible for ensuring quality checks are done on data and all other aspects of the study and will work in collaboration with the coordinator to ensure the study data and processes are of the highest quality. The data clerks will be responsible for entering all the participants' data in the appropriate database and checking data for accuracy, completeness, and consistency. They will also file participants’ binders in an orderly sequence.</p>\n<p>\n <strong>ICT Officers (1)</strong></p>\n<p>\n The ICT officer will be responsible for ensuring that the internet connectivity is of the right quality and speed to enable study activities such as online training, meetings, and data capture to be done with very minimal interruption. He/She will be in charge of the network administration of the study.</p>\n<p>\n <strong>Receptionist (1)</strong></p>\n<p>\n Manages front desk, participant registration, scheduling, reimbursements, and ensures readiness for visits.</p>\n<p>\n <strong>Driver (1)</strong></p>\n<p>\n The driver will assist with all projects driving and delivery needs. He/she will transport staff members to various Project activities and assist in the follow-up and recruitment of study participants and locating them where necessary during the accelerated mobilization. He/she will also be responsible for vehicle maintenance and keeping track of vehicle work tickets/logs.</p>\n<p>\n <strong>Office assistant (1)</strong></p>\n<p>\n Maintains cleanliness and infection control measures at the site.</p>\n<p>\n Site Infracstructure:</p>\n<p>\n The clinical trial facility has a total of 18 rooms. This includes a reception area, a pharmacy and a laboratory with controlled access, 2 counselling rooms, 4 clinic rooms, 2 data rooms with secure record archives, restrooms, meeting and office spaces. The space is adequate to support more than 25 study staff. The Pharmacy has a refrigerator for the storage of study products. Facilities and equipment are supported and maintained through regular contracts and service agreements.</p>\n<p>\n The Laboratory is a GCLP-certified sample processing laboratory with capacity for Centrifugation, aliquoting, and temporary storage of biological specimens (including a 2-8°C refrigerator and a -80°C freezer with backup power supply, on-site rapid HIV testing, pregnancy testing, and urine testing, sample shipment coordination to central labs internationally under IATA-compliant cold chain logistics. This laboratory also participates in quality assurance programs.</p>\n<p>\n For Data Management, there are secure data entry and transmission systems, including REDCap and electronic data capture (EDC) platforms, with daily data backup, query resolution processes, and restricted access controls.</p>\n
      • other_details_explanation<p>\n Despite major strides in the global HIV response, AGYW in sub-Saharan Africa remain disproportionately affected by HIV, with infection rates significantly higher than their male peers. In Kenya alone, over 1.4 million people are living with HIV, and Homa Bay County consistently reports one of the highest HIV prevalence rates in the country, particularly among young women aged 16–30. This high burden underscores the urgent need for expanded and effective HIV prevention options tailored to this population.</p>\n<p>\n Daily oral pre-exposure prophylaxis (PrEP) using a combination of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) has demonstrated high efficacy in preventing HIV infection when taken consistently. However, real-world adherence among AGYW has been suboptimal due to numerous structural and behavioural challenges, including stigma, partner dynamics, pill fatigue, daily lifestyle constraints, and fear of unintended disclosure. As a result, the full public health impact of oral PrEP has not been realized among those at greatest risk.</p>\n<p>\n There is increasing interest in long-acting PrEP methods that reduce the need for daily adherence while maintaining protective efficacy. MK-8527, with its monthly oral formulation and promising early-phase data, represents a significant step toward expanding the HIV prevention toolkit. Its once-monthly dosing could improve uptake, persistence, and effectiveness in AGYW—populations who need it most.</p>\n<p>\n The current Phase III study (MK-8527-010-00) will compare monthly MK-8527 to daily FTC/TDF in terms of efficacy, safety, tolerability, adherence, and acceptability among cisgender women aged 16 to 30 years. The inclusion of adolescent participants is of particular importance given the epidemiological evidence and the significant gap in biomedical HIV prevention research focused on this group.</p>\n<p>\n The Rachuonyo Clinical Research Site in Homa Bay County is uniquely positioned to contribute to this trial. The region has a well-documented HIV epidemic, strong community health structures, and experience in clinical trials targeting vulnerable populations including adolescent girls and sex workers. Importantly, this site can provide essential data on the implementation of monthly oral PrEP in a rural, resource-limited context, complementing findings from urban and international sites.</p>\n<p>\n By evaluating MK-8527’s performance in such settings, this study aims to inform future PrEP delivery models and expand the HIV prevention toolkit with options that are better suited to the realities of AGYW in high-incidence regions. If proven effective and acceptable, once-monthly oral MK-8527 could have a transformative impact on HIV prevention strategies and help close the gap in new infections among women in sub-Saharan Africa.</p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p>\n Still pending </p>\n
      • other_details_regulatory_approved<p>\n pending </p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None </p>\n
      • estimated_duration27 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatoremtricitabine/tenofovir
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states3
      • number_of_sites4
      • multi_country_listSouth Africa, Uganda, Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_siteA minimum of 150 participant
      • total_participants_worldwideA total of 4580 participants.
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameElizabeth
      • investigator1_middle_nameAnne
      • investigator1_family_nameBukusi
      • investigator1_qualificationMBChB, M.Med (ObGyn), MPH, PhD, PGD (Research Ethics), MBE (Research Ethics)
      • investigator1_professional_addressKEMRI-CMR-RCTP KEMRI CIS Building Ondiek Road, Lumumba Sub-County Hospital P.O. Box 614-40100 Kisumu, Kenya Telephone: 0202600017
      • investigator1_telephone+254 733617503
      • investigator1_emailebukusi@rctp.or.ke
      • organisations_transferred_Yes
      • number_participantsApproximately 600
      • notification<p>\n No other comments for now </p>\n
      • approval_date15-12-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-10-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted12-09-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been approved
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2026-04-01 15:49:31
      • created2025-08-05 17:04:52
      • total_sites1
      • ecitizen_invoice384719
      • ai_content(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1349
        • application_id1585
        • given_nameIrene
        • middle_nameWambui
        • family_nameInwani
        • qualificationMBChB, MMed, MPH
        • professional_addressUW-KNH; Rachuonyo County Hospital, Oyugis Kendu Bay Road Postal/Zip Code 40222 Homabay County, Kenya
        • telephone+254722608483
        • emailiinwani@yahoo.com
        • investigator_roleprincipal
        • created2025-08-13 10:04:51
        • modified2025-10-03 15:45:59
    • SiteDetail(array)
      • 0(array)
        • id1983
        • application_id1585
        • county_id43
        • site_nameUW-KNH; Rachuonyo County Hospital, Oyugis
        • physical_addressRachuonyo County Hospital, Oyugis Kendu Bay Road Postal/Zip Code 40222
        • contact_detailsKendu Bay Road Postal/Zip Code 40222, +254 758 070 841
        • contact_personDr. Irene Inwani
        • site_capacity(null)
        • misc(null)
        • created2025-08-13 10:04:51
        • modified2025-10-03 15:45:59
        • County(array)
          • id43
          • county_nameHoma Bay
          • created2012-06-15 10:27:10
          • modified2012-06-15 10:27:10
      • 1(array)
        • id1984
        • application_id1585
        • county_id42
        • site_nameKEMRI-CMR-RCTP KEMRI CIS Building
        • physical_addressKEMRI CIS Building
        • contact_detailsOndiek Road, Lumumba Sub-County Hospital P.O. Box 614-40100 Kisumu, Kenya Telephone: 0202600017
        • contact_personDr. Elizabeth Bukusi
        • site_capacity(null)
        • misc(null)
        • created2025-08-13 11:10:53
        • modified2025-10-03 15:45:59
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1985
        • application_id1585
        • county_id42
        • site_nameKargeno Research & Policy Hub
        • physical_addressLocated on Karume Road / Jairo Street Junction, opposite the Administration Police (AP) Line Dispensary)
        • contact_detailsP.O. Box 19669-40123, Kisumu, Kenya
        • contact_personDr. Maricianah Onono
        • site_capacity(null)
        • misc(null)
        • created2025-08-13 11:10:53
        • modified2025-10-03 15:45:59
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 3(array)
        • id1986
        • application_id1585
        • county_id22
        • site_nameKEMRI-CCR-PHRD, Thika site
        • physical_addressPartners in Prevention House, OAU Road, Thika, Kiambu County, Kenya
        • contact_detailsP.O. Box 19865, 00202, Nairobi
        • contact_personDr. Nelly Mugo
        • site_capacity(null)
        • misc(null)
        • created2025-08-13 11:10:53
        • modified2025-10-03 15:45:59
        • County(array)
          • id22
          • county_nameKiambu
          • created2012-06-15 10:24:37
          • modified2012-06-15 10:24:37
    • Sponsor(array)
      • 0(array)
        • id863
        • application_id1585
        • sponsorMerck Sharp & Dohme LLC (hereafter called the Sponsor or MSD)
        • sponsor_typeIndustry
        • contact_personSue Bailey
        • address 117 16th Road, Halfway House 1685 South Africa
        • telephone_number +27116553307
        • fax_number
        • cell_number +27116553307
        • email_addresssue.bailey@msd.com
        • created2025-08-13 10:04:51
        • modified2025-10-03 15:45:59
  • 4(array)
    • Application(array)
      • id148
      • user_id613
      • trial_status_id5
      • abstract_of_study<p>\n <br />\n Cryptococcal meningitis [CM] is the commonest complication of the central nervous system [CNS] accounting for many AIDS associated deaths in Kenya and other parts of the developing world .The preferred regimen of CM treatment is the two week induction with intravenous amphotericin B infusions followed by a course oral fluconazole. The administration of ampho-B in resource poor setting poses a challenge due to its requisite safety monitoring and prohibitive cost and therefore the use fluconazole as a single oral agent is quite desirable.<br />\n This study is randomized, open label clinical trial being carried out in over 10 sites worldwide by the AIDS Clinical Trials Group (ACTG).The overall aim of the study is to establish a Maximum Tolerable Dose [MTD] of fluconazole which can be safely and effectively used as a single oral agent in the management of AIDS associated cryptococcal meningitis.<br />\n The study will be conducted in two stages ; Stage 1, Dose Escalation, up to three induction doses of fluconazole will be tested in sequentially enrolled cohorts. At this stage, safety will be evaluated i.e the maximum tolerable dose of fluconazole will be determined.<br />\n Stage 2, Dose Validation, induction doses of fluconazole that were found to be safe in Stage 1 will be tested against Amphotericin B for efficacy in simultaneously enrolled cohorts. This comparison aims to identify the lower dose of fluconazole with the highest efficacy. This will also serve as a pilot for a larger phase III efficacy trial and obtain additional AE reports in a larger study population.<br />\n The Kericho Site will recruit between 20-30 HIV-1 infected males and females 18 years and above presenting with their first episode of cryptococcal meningitis who have not received ART within 30 days prior to study entry.<br />\n Recruitment will primarily be done through the Kericho District Hospital HIV clinic. All enrolled participants will be followed up for 24 weeks. Due to the nature of the study (pauses between doses in Stage 1 and to confirm efficacy prior to initiating Stage 2), it is difficult to estimate the duration of accrual on this study. However it is anticipated that accrual may be completed approximately 1 year after all eligible sites are able to begin enrolling.</p>\n
      • study_title<p align=\"center\">\n <strong>A Phase I/II Dose-Finding Study of High-Dose Fluconazole Treatment in AIDS-Associated Cryptococcal Meningitis</strong></p>\n<p align=\"center\">\n  </p>\n<p align=\"center\">\n <strong>A Multicenter Trial of the AIDS Clinical Trials Group (ACTG)</strong></p>\n
      • laymans_summary<p>\n Cryptococcal Meningitis is a common infection in people with AIDS. The purpose of this study is to help find out if a new treatment for Cryptococcal Meningitis using high doses of oral fluconazole is a safe and effective alternative to the existing treatment using Intra-Venous amphotericin B. This study is being done to see if taking fluconazole alone at a dose of 1200 mg per day, 1600 mg per day, or 2000 mg per day is tolerable, safe, and effective for the treatment of Cryptococcal Meningitis for up to 10 weeks. Fluconazole is a drug that is taken by mouth that is approved throughout the world and in Kenya by the Pharmacy and Poisons Board in doses up to 400 mg per day for the treatment of Cryptococcal Meningitis. Currently, fluconazole is given alone mainly for people with mild cases of Cryptococcal Meningitis. Doses higher than 400 mg per day have not been approved by the U.S. Food and Drug Administration. The study will also collect information about treating Cryptococcal Meningitis with amphotericin B (alone or with another drug, either flucytosine or fluconazole). Amphotericin B is a drug that must be given to you through a vein in your arm. The study was planned in two stages whereby stage 1 was Dose escalation and stage 2 dose validation.</p>\n<p>\n The Kericho Site will recruit between 20-30 HIV-1 infected males and females 18 years and above presenting with their first episode of cryptococcal meningitis in those who are on antiretroviral therapy or in those who have not initiated ART. Kericho site recruited 13 participants in stage 1 and will recruit up to 15 participants in stage 2</p>\n
      • short_titleA5225/ HiFLAC
      • protocol_noECCT/10/09/05
      • version_no2.0
      • date_of_protocol11-05-2012
      • study_drugFluconazole
      • disease_conditionAIDS-Associated Cryptococcal Meningitis
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameFluconazole
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameIV Amphotericin B
      • comparator_registeredYes
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresssamwel.chirchir@usamru-k.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample0
      • applicant_gcp_training0
      • applicant_dsmb_charter0
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license0
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist0
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantSamwel K Chirchir -Study coordinator. KEMRI/WRP Kericho Box 1357 Kericho.
      • declaration_date114-06-2013
      • declaration_principal_investigatorDr Deborah Langat-PI.KEMRI/WRP kericho Box 1357 Kericho.
      • declaration_date214-06-2013
      • placebo_presentNo
      • study_objectives<div>\n Primary Objectives</div>\n<div>\n 1 To assess the MTD of fluconazole by comparing the safety and tolerability of induction regimens of 1200, 1600, and 2000 mg/day.</div>\n<div>\n 2 To determine whether the safety and efficacy of high induction-dose fluconazole therapy support development of a phase II/III trial, and, if so, to select the most appropriate fluconazole dose regimen (based on safety and efficacy data from this study) to be evaluated in that trial.</div>\n<div>\n  </div>\n<div>\n Secondary Objectives</div>\n<div>\n 1 To compare the clinical and fungicidal effects of different induction regimens of fluconazole during induction at weeks 2, 4, 6, 8, and 10.</div>\n<div>\n 2 To assess functional status (prior to onset of current CM illness, at study entry, at week 10, and at premature treatment or study discontinuation) and to assess neurological status [at entry, weeks 2, 10, 24, and at progression of symptoms and premature treatment or study discontinuation].</div>\n<div>\n 3 To assess the time to death in each cohort and the combined rates of DLT (Dose limiting toxicities) and death.</div>\n<div>\n 4 To describe the effect of baseline clinical, neurological, and mycological characteristics on clinical and mycological success at week 10 and on time to CSF sterility.</div>\n<div>\n 5 To assess the length of hospitalization between study entry and hospital discharge and for any subsequent readmission for the treatment of CM.</div>\n<div>\n 6 To assess the incidence of progression of symptoms and its components among all participants receiving ART during the study.</div>\n<div>\n 7 To estimate the tolerability, toxicity, and efficacy of an ampho B-based regimen in the setting of non-U.S. sites for the purposes of planning additional studies.</div>\n<div>\n 8 To assess the relationship of antifungal drug susceptibility of cryptococcal isolates to fluconazole and microbiological and clinical outcomes.</div>\n<div>\n 9 To assess the pharmacology [pharmacokinetics (PK), pharmacodynamics (PD)], and toxicity of high-dose fluconazole and, if samples are available, relationships with concomitant RIF and/or efavirenz (EFV) (see section 10.1 for specific pharmacology objectives].</div>\n<div>\n  </div>\n<div>\n Exploratory Objectives</div>\n<div>\n 1 To assess the relationship of antifungal drug susceptibility of cryptococcal isolates to fluconazole and microbiological and clinical outcomes.</div>\n<div>\n 2 To assess the pharmacology [pharmacokinetics (PK), pharmacodynamics (PD)], and toxicity of high-dose fluconazole and, if samples are available, relationships with concomitant RIF and/or efavirenz (EFV) (see section 10.1 for specific pharmacology objectives].</div>\n<div>\n 3 To evaluate a lateral flow cryptococcal antigen (LFCrAg) detection assay using urine, serum, plasma, and CSF samples from participants with confirmed CM.</div>\n
      • principal_inclusion_criteria<p>\n Inclusion Criteria-Step 1<br />\n 10.3.1.1 Cryptococcal meningitis documented either by a positive CSF cryptococcal culture, a positive CSF India ink preparation, or a positive CSF cryptococcal antigen latex agglutination test within 7 days prior to entry.<br />\n For the Kericho Site, a positive CSF India ink preparation or a positive CSF cryptococcal antigen latex agglutination test performed at the KEMRI/CRC laboratory will be used for eligibility.<br />\n 10.3.1.2 CSF collection for quantitative cryptococcal culture within 72 hours prior to study entry or planned to be performed at study entry.<br />\n 10.3.1.3 HIV-1 infection documentation; For the Kericho Site, HIV-1 infection will be confirmed at screening based upon 2 serial rapid HIV tests that will be done at the KEMRI/WRP CRC Kericho according to MOH guidelines. Volunteers entering the study will have HIV infection re-confirmed by 2 serial ELISA and Western Blot tests consistent with the KEMRI/WRP laboratory algorithm.<br />\n NOTE: HIV infection must be re-confirmed by day 10 of the study, using the standard and approved Kericho laboratory algorithm of 2 serial ELISA followed by a Western Blot. Enrollment procedures and administration of study drugs will only begin after the HIV screening results (2 serial rapid tests) are obtained.<br />\n 10.3.1.4 Men and women age ≥ 18 years.<br />\n 10.3.1.5 Ability to take oral medications.<br />\n NOTE: Administration of fluconazole tablets via nasogastric tube is permitted.<br />\n 10.3.1.6 For patients with a co-morbid complication of HIV, including opportunistic infections, receipt of stable treatment for the co-morbid complication and clinically stable, as judged by the site investigator.<br />\n NOTE: Stable treatment is defined as treatment that has been taken for at least 2 weeks without change in dose or formulation of any of its components.<br />\n 10.3.1.7 For female participants of reproductive potential (defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or have not undergone surgical sterilization [e.g., hysterectomy, or bilateral oophorectomy or salpingotomy]) a negative serum or urine pregnancy test result must be obtained within 2 days prior to study entry.<br />\n 10.3.1.8 All participants must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization).<br />\n If participating in sexual activity that could lead to pregnancy, all participants must use two forms of contraception (listed below) while on study treatment and for 6 weeks after fluconazole (at any dose greater than a single 150 mg dose) has been discontinued.<br />\n Two of the following contraceptives MUST be used appropriately:<br />\n • Condoms (male or female) with or without a spermicidal agent<br />\n • Diaphragm or cervical cap with spermicide<br />\n • IUD (intrauterine device)<br />\n • Injectable DepoProvera<br />\n • Tubal Ligation<br />\n NOTE: Use of oral hormone-based contraceptives is prohibited while a participant is taking a daily dose of fluconazole that is greater than 200 mg.<br />\n 10.3.1.9 Participants who are not of reproductive potential (defined as women who have been post-menopausal for at least 24 consecutive months, or women who have undergone surgical sterilization [e.g., hysterectomy, or bilateral oophorectomy or salpingotomy]), or men who have documented azoospermia), are eligible without the requirement to use contraception.<br />\n NOTE: Lack of reproductive potential requires written documentation or oral communication from a clinician or clinician’s staff documented in source documents.<br />\n 10.3.1.10 Willingness and ability to adhere to dose schedules and mandatory procedures<br />\n 10.3.1.11 Measured or calculated creatinine clearance of ≥50 mL/min within 3 days prior to study entry obtained at the KEMRI/CRC laboratory.<br />\n The Cockcroft-Gault method will be used to calculate creatinine clearance:<br />\n For men: [(140 - age in years) x (body weight in kg)] ÷ (serum creatinine in mg/dL x 72).<br />\n For women: use the same calculation as for men, then multiply the result by 0.85.<br />\n 10.3.1.12 The following laboratory values within 3 days prior to study entry obtained at the KEMRI/WRP laboratory:<br />\n • aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 5 X the upper limit of normal (ULN)<br />\n • total bilirubin ≤ 2.5 X ULN<br />\n • absolute neutrophil count (ANC) ≥ 750/mm3<br />\n • platelet count ≥ 50,000/mm3<br />\n • hemoglobin ≥ 7.0 g/dL<br />\n 10.3.1.13 Ability and willingness of the participant or next of kin to give informed consent.<br />\n 10.3.1.14 Availability at the site of at least 2 weeks of its standard of care ampho B-based regimen.</p>\n
      • principal_exclusion_criteria<p>\n Exclusion Criteria - Step 1<br />\n 10.3.2.1 Expected survival of ≤ 2 weeks, in the opinion of the site investigator.<br />\n 10.3.2.2 For patients with a co-morbid complication of HIV, anticipated difficulty, in the opinion of the site investigator, in judging response to study treatment as a result of the co-morbid complication or the drugs used to treat it.<br />\n 10.3.2.3 Breast-feeding.<br />\n 10.3.2.4 A prior episode of CM, either as indicated by patient or as noted in patient medical records.<br />\n 10.3.2.5 Use of any of the following drugs, within the time periods described:<br />\n • any ARV within 30 days prior to study entry<br />\n • rifampin within 2 weeks prior to study entry<br />\n • warfarin within 3 days prior to study entry<br />\n • terfenadine or cisapride within 24 hours prior to study entry<br />\n • other drugs known to interact with fluconazole, the co-administration of which may lead to life-threatening side effects, within 10 days prior to study entry as per the current A5225/HiFLAC MOPs.<br />\n • drugs that may decrease the effect of fluconazole, or whose co-administration may increase their own toxicity or decrease their own efficacy, within 24 hours prior to study entry as per the current A5225/HiFLAC MOPs.<br />\n • phenytoin, carbamazepine, cyclosporin A, tacrolimus, sirolimus, astemizole, or long-acting barbiturates within 7 days prior to study entry<br />\n • more than 72 cumulative hours of systemic treatment with any antifungal for any reason within 14 days prior to study entry.<br />\n 10.3.2.6 Suspected or active tuberculosis (TB), even if untreated, for participants screening at the time that a 1200 mg daily fluconazole induction cohort is enrolling. A chest x-ray may be used to confirm suspected tuberculosis, but is not required.<br />\n 10.3.2.7 Known allergy, sensitivity to, or intolerance of fluconazole or other imidazole or triazole compounds, or to ampho B or other components of the standard of care ampho-B based regimen.<br />\n 10.3.2.8 History of clinically significant cardiac disease, in opinion of site investigator, including symptoms of ischemia, coronary artery disease, congestive heart failure, or arrhythmia.<br />\n 10.3.2.9 ECG (electrocardiogram) with QTc interval greater than 450 msec within 7 days prior to study entry.<br />\n 10.3.2.10 History of CNS disorder (excluding mood disorders) or concurrent CNS disorder(s) that, in the opinion of the investigator, would interfere with assessment of efficacy (e.g., ability to perform CSF sampling) such as lymphoma, neurocysticercosis, or toxoplasmosis.<br />\n 10.3.2.11 Receipt of investigational drug therapy within 30 days prior to study entry without prior approval of the A5225/HiFLAC core team.<br />\n 10.3.2.12 Receipt of any of the following for treatment of the current episode of CM:<br />\n • more than 2400 mg of fluconazole cumulative<br />\n • more than 1.5 mg/kg of ampho B cumulative<br />\n • more than 750 mg/kg of flucytosine cumulative<br />\n • more than 72 cumulative hours of any systemic antifungal therapy<br />\n 10.3.2.13 Active drug or alcohol use, dependence, or other conditions that in the opinion of the site investigator would jeopardize the safety of a participant in the study or would render the person unable to comply with the study plan.</p>\n
      • primary_end_points<p>\n The primary efficacy outcome measure is the change in quantitative CSF culture for cryptococcus. During screening or at entry, CSF samples for culture will be collected from all participants. At week 2, CSF samples will again be collected from all participants and will be cultured. Additional CSF samples will be collected and cultured at weeks 4, 6, 8, and 10, until a negative culture following 2 weeks of incubation is obtained. Treatment failure for any participant is defined as a week 10 CSF culture (which is read by or at week 12) that is positive for <em>C. neoformans</em>.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyHigh dose finding study
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Please refer to the attached SSA section 1 page 3-5</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n 1.KEMRI ERC</p>\n<p>\n 2.WRAIR IRB</p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration3Years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorAmphotericin B Deoxychola
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states6
      • number_of_sites
      • multi_country_listKenya, South Africa, Uganda, Thailand, Zimbabwe, United States
      • data_monitoring_committeeYes
      • total_enrolment_per_site9
      • total_participants_worldwide96
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameSamwel
      • investigator1_middle_name
      • investigator1_family_nameChirchir
      • investigator1_qualificationBSc Nursing
      • investigator1_professional_addressKenya Medical Research Institute/Walter Reed Project,P.O. BOX 1357,Hospital Road, Kericho, Kenya, 20200
      • investigator1_telephone052 20 36100
      • investigator1_emailsamwel.chirchir@usamru-k.org
      • organisations_transferred_Yes
      • number_participants32
      • notification<p>\n N/A</p>\n
      • approval_date08-02-2013
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-05-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"702\">\n <tbody>\n <tr>\n <td style=\"width:702px;height:18px;\">\n <p>\n <strong>Study Status at Close-out:</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:85px;\">\n <p>\n [X] Study was completed</p>\n <p>\n [] Study was started but closed prior to completion</p>\n <p>\n [] Study was not started</p>\n <p>\n [] Study is being transferred to another institution</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:24px;\">\n <p>\n <strong>Summary of research objectives:</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:24px;\">\n <p>\n This was a two-stage, randomized, open-label phase I/II dose escalation and validation study of the safety, tolerability, and therapeutic effect of an induction-consolidation strategy of high-dose fluconazole alone for the treatment of cryptococcal meningitis (CM) in HIV-infected participants in comparison to amphotericin B deoxycholate alone or in combination with 5-fluorocytosine or fluconazole, according to local standard of care.</p>\n <p>\n  </p>\n <p>\n A total of 22 participants were screened and 16 enrolled at Kericho; Of the 16 participants enrolled, 6 died, 2 were withdrawn from the study because of negative cryptococcal cultures, 8 participants completed study visits and currently no participant is on follow up. Accrual to the study was closed on 19 August 2016. A total of 168 participants were enrolled in all the international sites for this study.</p>\n <p style=\"margin-left:.25in;\">\n <strong>Primary Objective</strong></p>\n <ol>\n <li>\n To assess the MTD of fluconazole by comparing the safety and tolerability of induction regimens of 1200, 1600, and 2000 mg/day.</li>\n <li>\n To determine whether the safety and efficacy of high induction-dose fluconazole therapy support development of a phase II/III trial, and, if so, to select the most appropriate fluconazole dose regimen (based on safety and efficacy data from this study) to be evaluated in that trial.</li>\n </ol>\n <p style=\"margin-left:.5in;\">\n <strong>Secondary Objectives</strong></p>\n <ol>\n <li>\n To compare the clinical and fungicidal effects of different induction regimens of fluconazole during induction at weeks 2, 4, 6, 8, and 10. </li>\n <li>\n To assess functional status (prior to onset of current CM illness, at study entry, at week 10, and at premature treatment or study discontinuation) and to assess neurological status [at entry, weeks 2, 10, 24, and at progression of symptoms and premature treatment or study discontinuation]. </li>\n <li>\n To assess the time to death in each cohort and the combined rates of DLT (Dose limiting toxicities) and death.</li>\n <li>\n To describe the effect of baseline clinical, neurological, and mycological characteristics on clinical and mycological success at week 10 and on time to CSF sterility.</li>\n <li>\n To assess the length of hospitalization between study entry and hospital discharge and for any subsequent readmission for the treatment of CM.</li>\n <li>\n To assess the incidence of progression of symptoms and its components among all participants receiving ART during the study. </li>\n <li>\n To estimate the tolerability, toxicity, and efficacy of an ampho B-based regimen in the setting of non-U.S. sites for the purposes of planning additional studies.</li>\n </ol>\n <p style=\"margin-left:.25in;\">\n <strong>Exploratory Objectives</strong></p>\n <ol>\n <li>\n To assess the relationship of antifungal drug susceptibility of cryptococcal isolates to fluconazole and microbiological and clinical outcomes.</li>\n <li>\n To assess the pharmacology [pharmacokinetics (PK), pharmacodynamics (PD)], and toxicity of high-dose fluconazole and, if samples are available, relationships with concomitant RIF and/or efavirenz (EFV) (see section 10.1 for specific pharmacology objectives].</li>\n <li>\n To evaluate a lateral flow cryptococcal antigen (LFCrAg) detection assay using urine, serum, plasma, and CSF samples from participants with confirmed CM.</li>\n </ol>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:46px;\">\n <p>\n <strong>F. Summary of Study Results: </strong>Please summarize the results of this research project, even if only for the study cohort enrolled locally.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:35px;\">\n <p>\n  In stage 1 of the study, HIV-infected participants with CM were assigned to receive one of the 3 induction doses of fluconazole alone: 1200, 1600, or 2000 mg/day or IV amphotericin B. These regimens were tested sequentially in stage 1 so that safety could be assessed at each level before the decision was made to expose new participants to the next higher dose. The 1200 mg fluconazole arm showed evidence of inferior efficacy compared to the amphotericin control arm. Fluconazole was tolerated up to 2000 mg/day. There were no clear differences in safety or efficacy of either the 1600 mg or 2000 mg fluconazole arms compared to the amphotericin control arm.</p>\n <p>\n  </p>\n <p>\n In stage 2 of the study, the induction doses of fluconazole that were found to be safe in Stage 1 (1600 mg/day and 2000 mg/day) and IV amphotericin were tested in simultaneously enrolled cohorts. Induction phase weight and renal-adjusted doses of 1600mg and 2000mg/day fluconazole for CM were safe and well tolerated except for increased GI side effects in the 2000mg/day dose, and had similar times to achieve CSF sterilization, but took significantly longer than Amphotericin B. The WHO recommended 1200mg fluconazole was associated with a high mortality. While not statistically significant, mortality was numerically lower in the amphotericin B compared to 1600mg and 2000mg fluconazole.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:41px;\">\n <p>\n <strong>G. List Outputs arising from study e.g. Manuscripts, Thesis, Research Reports, Technical Briefs, Policy Briefs, Abstracts, Patents, Book Chapter etc. (attach copies of the outputs(s). </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:48px;\">\n <ol style=\"list-style-type:lower-alpha;\">\n <li>\n A5225 Manuscript: Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)-report of A5225, a multicentre, phase I/II, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group</li>\n </ol>\n <p>\n  </p>\n <ol style=\"list-style-type:lower-alpha;\">\n <li value=\"2\">\n A5225 Oral Abstract presented at the CROI Conference on March 4-7, 2018 at Boston Massachusetts, - Higher High Dose Fluconazole for the Treatment of Cryptococcal Meningitis.</li>\n </ol>\n <p>\n  </p>\n <ol style=\"list-style-type:lower-alpha;\">\n <li value=\"3\">\n Poster presented at the 9th International Conference on Cryptococcus and Cryptococcosis (9th ICCC) in 2014. High-dose fluconazole for the treatment of Cryptococcal meningitis in HIV-infected individuals.</li>\n </ol>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:14px;\">\n <ol style=\"list-style-type:upper-alpha;\">\n <li value=\"8\">\n <strong>Confirm destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked-out books). </strong></li>\n </ol>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:31px;\">\n <p>\n Study documents have been transferred to a safe, secured, long-term archive room that is only accessible to regulatory personnel. All other research staff do not have access to this archive room. Access to study documents is controlled and restricted and the site is responsible for ensuring that any access is accurately recorded and any documents accessed/removed and returned are recorded. Destruction approval will be obtained from the sponsor and the IRBs will be notified when this is done.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>I. Detail the plan for future use of data from the study (if applicable) </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:33px;\">\n <ul style=\"list-style-type:circle;\">\n <li>\n There are currently no plans for future analysis of individual participant data by study site personnel. Analysis of aggregated data and publication for secondary objectives will continue.</li>\n </ul>\n <p style=\"margin-left:.5in;\">\n  </p>\n <ul style=\"list-style-type:circle;\">\n <li>\n Any plans for future (non-aggregated) analyses will be reviewed and approved by KEMRI SERU prior to the work being completed.</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>J. Confirm destruction of surplus investigational agents and provide an assurance/evidence that the destruction has occurred (if applicable) </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:25px;\">\n <table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:646px;height:18px;\">\n <p>\n Find attached destruction documents.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:646px;height:4px;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n </table>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>K. Detail the plan for the destruction, storage, or future use of biological specimens obtained as part of this study (include number of samples being destroyed or stored) </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:42px;\">\n <p style=\"margin-left:.25pt;\">\n All work for this study is complete and the samples that were not for safety testing were all shipped out with the approval of KEMRI ERC for analysis. Future use of individually coded data will have to be approved by the IRB. Participants were informed through the informed consent forms that they signed, that the stored samples may be shipped out of the country and used for future ACTG -approved HIV related research, which will help understand Cryptococcal Meningitis/HIV better. The participants were also made aware that any use of the samples and stored data whether locally or out of the country will have to be approved by Kenya Medical Research Institute Ethical Review Committee.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>L. Were the study results communicated to the local community? If yes provide details where and when- if not kindly explain why not.</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:27px;\">\n <p>\n The study results have been communicated to the local community through continuous medical education and meeting with the community Advisory Board as well as meetings organized in the community.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>M. Is there a policy implication or best practice that should be forwarded to the MOH or any relevant authority?  </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:47px;\">\n <p>\n Yes, from the Publication:</p>\n <ul style=\"list-style-type:circle;\">\n <li>\n The WHO recommends high dose 1200 mg fluconazole (FLU) if amphotericin B (AmB) is not available or not feasible to use in persons with AIDS associated cryptococcal meningitis (CM) in resource limited settings. The safety and efficacy of high dose (1200-2000mg/d) oral FLU for the initial treatment of AIDS-associated CM in an AmB-controlled 2-stage dose escalation study is recommended.</li>\n </ul>\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • implication_results<p>\n Yes, from the Publication:</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n The WHO recommends high dose 1200 mg fluconazole (FLU) if amphotericin B (AmB) is not available or not feasible to use in persons with AIDS associated cryptococcal meningitis (CM) in resource limited settings. The safety and efficacy of high dose (1200-2000mg/d) oral FLU for the initial treatment of AIDS-associated CM in an AmB-controlled 2-stage dose escalation study is recommended.</li>\n</ul>\n
      • quantity_imported38
      • quantity_dispensed38
      • quantity_destroyed0
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2023-04-13 12:52:59
      • created2013-06-05 11:09:19
      • total_sites(null)
      • ecitizen_invoice(null)
      • ai_content(null)
    • InvestigatorContact(array)
      • 0(array)
        • id91
        • application_id148
        • given_nameDeborah
        • middle_nameChepngeno
        • family_namelangat
        • qualificationMBChB, MSc
        • professional_addressKenya Medical Research Institute/Walter Reed Project,P.O. BOX 1357,Hospital Road, Kericho, Kenya, 20200
        • telephone052 20 36100
        • emaildeborah.langat@usamru-k.org
        • investigator_roleprincipal
        • created2013-06-05 11:12:27
        • modified2020-05-19 15:02:31
    • SiteDetail(array)
      • 0(array)
        • id113
        • application_id148
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2013-06-05 11:12:27
        • modified2020-05-19 15:02:31
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id72
        • application_id148
        • sponsorThe National Institute of Allergy and Infectious Diseases
        • sponsor_typeResearch Institution
        • contact_person
        • addressHIV Research Branch TRP, DAIDS, NIAID, NIH 6700B Rockledge Drive Bethesda, MD 20892
        • telephone_number+1-301- 451-2761
        • fax_number
        • cell_number+1-301- 451-2761
        • email_addressactg.user.support@fstrf.org
        • created2013-06-05 11:12:27
        • modified2020-05-19 15:02:31
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(empty)
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php