Pharmacy and Poisons Board: Applications

List Applications

Protocol No:

ECCT/16/08/01

Date of Protocol:

14-05-2015

Study Title:	A5349/TBTC S31 “Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis: A randomized, open-label, controlled phase 3 clinical trial”
Study Objectives:	Primary: To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis Secondary: To evaluate the safety of the investigational regimens To evaluate the tolerability of the investigational regimens To collect and assess biospecimens from consenting participants for the purpose of research on discovery and validation of TB biomarkers To determine the correlation of mycobacterial and clinical markers with time to culture conversion, culture status at completion of eight weeks of treatment, treatment failure, and relapse. To conduct a pharmacokinetic/pharmacodynamic (PK/PD) study of the test drugs. The main objectives of the PK/PD study are to characterize study drug PK parameters and to determine relationships between treatment outcomes and PK parameters. To evaluate the pharmacokinetics of efavirenz-based antiretroviral treatment among patients with TB/HIV co-infection taking efavirenz-based combination antiretroviral therapy and TB treatment with rifapentine
Laymans Summary:	Standard TB treatment takes 6 months. Stronger drugs might allow treatment to be shorter. Two new drugs are called rifapentine and moxifloxacin. These drugs look stronger than standard drugs in international research studies. This study tests if they are strong enough to make TB treatment shorter. This study will also see what side effects are caused by taking rifapentine and moxifloxacin for 4 months. This study seeks to find out if taking higher doses of rifapentine alone and in combination with moxifloxacin for a shorter amount of time works as well as the “standard” 6-month TB treatment.
Abstract of Study:	Hypotheses: A) Seventeen (17) week rifapentine-based regimen In previously untreated individuals with active drug-susceptible pulmonary tuberculosis treated with eight weeks of rifapentine (P), isoniazid (H), pyrazinamide (Z) and ethambutol (E) followed by nine weeks of rifapentine plus isoniazid, all given daily throughout, the proportion of participants who experience absence of cure (unfavorable outcome) will not be inferior to that observed in participants who are treated with a standard regimen (eight weeks of rifampin (R), isoniazid, pyrazinamide and ethambutol followed by eighteen weeks of rifampin plus isoniazid), all given daily throughout. B) Seventeen (17) week rifapentine- plus moxifloxacin-containing regimen In previously untreated individuals with active drug-susceptible pulmonary tuberculosis treated with eight weeks of rifapentine, isoniazid, pyrazinamide and moxifloxacin (M), followed by nine weeks of rifapentine, isoniazid, and moxifloxacin, all given daily throughout, the proportion of participants who experience absence of cure (unfavorable outcome) will not be inferior to that observed in participants who are treated with a standard regimen (eight weeks of rifampin, isoniazid, pyrazinamide and ethambutol followed by eighteen weeks of rifampin plus isoniazid), all given daily throughout. Phase: 3 Design: This will be an international, multicenter, randomized, controlled, open-label, 3-arm, phase 3 non-inferiority trial. Population: Patients with newly diagnosed, previously untreated pulmonary tuberculosis. Number of Sites: Multiple international sites, primarily sites of the Tuberculosis Trials Consortium and the AIDS Clinical Trials Group. Study Duration: Duration per participant is approximately 18 months.