A Study to Investigate the Safety, Tolerability and Pharmacokinetics of OZ439 in Healthy Male and Female Subjects
OZ439 is a synthetic trioxolane that has potential value as a peroxide antimalarial agent.
Part A will investigate the safety, tolerability and pharmacokinetics (PK) of single oral escalating doses of OZ439. Up to 6 dose levels will be investigated to estimate dose proportionality. In Part B, the effect of food on a single oral dose of OZ439 will be investigated in a 2-way crossover design. Part C will investigate the safety, tolerability and PK profile of multiple oral doses of OZ439.
The starting oral dose will be 50 mg and the maximum single dose to be administered will not exceed 1600 mg per subject. The maximum duration of dosing proposed is 3 days. The starting dose of 50 mg/kg is appropriate for OZ439 since this is not the first drug from this class and previously arteflene and arterolane were found to be safe and well tolerate in Phase I and Phase II studies. The toxicology studies to date show that a 50 mg dose of OZ439 is equivalent to 0.1 mg/kg dose which is 200 to 300 times lower than the NOEAL for dogs and rats in a 14 day toxicity study.
OZ439 is a new drug proposed for further investigation in a Phase I clinical safety and PK study in healthy male and female subjects. The preclinical safety profile of oral administration of OZ439 supports first administration to humans using an initial dose of 50 mg.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase I Study To Investigate The Safety, Tolerability And Pharmacokinetic Profile Of OZ439 In Healthy Male and Female Subjects|
- Safety evaluation will study the adverse event (AE) profile, clinical laboratory safety tests, vital signs, 12 lead and continuous ECG monitoring, and audiometry/Brainstem Auditory Evoked Potentials (BAEP) parameters. [ Time Frame: Continuous during study conduct ] [ Designated as safety issue: Yes ]
- Appropriate PK parameters, e.g. maximum observed plasma drug concentrations, time of occurrence of Cmax, area under the plasma concentration-time curves, the apparent terminal rate constant and corresponding half-life for OZ439. [ Time Frame: Continuous ] [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
|Study Completion Date:||December 2009|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
|Experimental: Single & multiple rising doses of OZ439||
Capsules of 50 and 200mg strength for oral dosing In part A Subjects will receive single doses of OZ439 on 3 occasions and placebo on 1 occasion over a period of approximately 10 weeks. In part B (food effect), subjects will receive 1 single dose of OZ439 on the morning of study Day 1 of each treatment period 1 and 2 for a total of 2 single doses.
In part C (multiple rising dose), the planned duration of treatment is OZ439/placebo once daily for 3 days. Final determination of the dosing regimen will depend on review of data from Part A