| Protocol No: | ECCT/13/07/05 | Date of Protocol: | 24-06-2013 |
| Study Title: | Single Dose Escalating, Single-blind Phase 1 Trial in Healthy Male Volunteers to Evalute the Safety, Tolerability and the Pharmacokinetics of Oleylphosphocholine. |
| Study Objectives: | |
| Laymans Summary: | |
| Abstract of Study: |
Visceral leishmaniasis is a systemic disease that is fatal if left untreated and worldwide
causes an estimated 50,000 deaths annually. In East Africa Visceral leishmaniasis
frequently causes large-scale tenacious epidemics with high case-fatality rates (CFRs).
For most of the past 70 years, the therapeutic armoury for treatment of leishmaniasis has
been extremely limited. Pentavalent antimonials were introduced in the 1940s. Use of
amphotericin B followed after a few decades, and was later joined by paromomycin, a
cheap and effective parenteral drug with an acceptable toxicity profile that can easily be
given by intramuscular injection. Finally, different lipid formulations of amphotericin B
(i.e. liposomal amphotericin B , Ambisome ) have been developed, which are similar to
amphotericin B in efficacy but with fewer toxic effects.
The development of miltefosine, the only drug at present that can be given orally for the
treatment of visceral leishmaniasis, has been a major breakthrough. Dafra Pharma
Research and Development intends to develop and commercialize a new and promising
alkylphosphocholine, oleylphosphocholine (OlPC), which is a derivative of miltefosine as
a new oral drug for the treatment of leishmaniasis.
The chemical structures of two alkylphosphocholines, oleylphosphocholine and
miltefosine are as shown below. The key difference between the two
alkylphosphocholines is that OLPC has a double bond in the alkyl chain that miltefosine
does not have.
Oleylphosphocholine presents an efficacy profile similar or superior to the one of
miltefosine in various experimental models, but has the advantage of showing a wider
therapeutic window compared to miltefosine translating into a better tolerance and
possible increased compliance to treatment, but it has not been administered to human in a
controlled clinical study.
Objectives
The primary objective is to estimate initial safety and tolerability of oleylphosphocholine
in healthy male volunteers.
The secondary objective is to obtain data on pharmacokinetics following oral
administration of oleylphosphocholine in human.
Methods
This protocol is intended to evaluate whether a rising dose of oleylphosphocholine,
administered orally in fasting condition, is well tolerated and safe in man. The protocol
uses 3 cohorts of 10 volunteers receiving a dose of 50, 100 or 150mg (on Day 0) of
oleylphosphocholine randomly allocated to the participants. The volunteers will also be
sampled for pharmacokinetic purposes.
Utility of results
This protocol is made for a first in man study of the compound oleylphosphocholine.
Single dose escalating, open Phase 1 trial in healthy male volunteers to evaluate the
safety, tolerability and the pharmacokinetics of oleylphosphocholine. The drug is
developed to become a treatment for Leishmaniasis in Africa. The results are intended to
be used to develop a phase-II study on the study.
In case the criteria for halting the study are not met at the end of the study, i.e. after all 30
volunteers have received their allocated study dose, tolerability beyond the intended
therapeutic dose might be explored to gain experience regarding target organs of toxicity
in case of intoxication during clinical use, or to allow higher doses for Phase II studies, if necessary.
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