Clinical Trial: Efficacy, Tolerability, PK of OZ439 in Adults With Acute, Uncomplicated P.Falciparum or Vivax Malaria Mono-infection

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase IIa Exploratory, Open Label, Single/Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and PK of OZ439 in Adult Patients With Acute, Uncomplicated P. Falciparu

Brief Summary: A Phase IIa Exploratory, Open label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in adult patients with acute, uncomplicated Plasmodium falciparum or vivax malaria mono-infection.

Detailed Summary:

This exploratory Phase IIa study aims to investigate the preliminary efficacy in terms of parasite reduction and clearance in malaria patients, and the tolerability of OZ439 administered as single dose regimen at 3 different doses in parallel cohorts of patients with either acute uncomplicated Plasmodium falciparum or Plasmodium vivax malaria mono-infection (10 patients per plasmodium species per dose level).

Treatment with OZ439 will be given as a single dose on Day 0, starting in the first cohort at a dose of 800 mg. Established antimalarial therapy will be given at the latest at 36 hours post dosing.

The primary endpoint will be the derived parasite reduction rate (PRR) at 24 hours after study drug administration.

A review of each individual study cohort (dose/species) will be conducted with the Principal Investigator and the Sponsor and a decision will be reached on whether the dose for the next cohort should increase or decrease (within 200mg-1600mg range). This decision will be based on parasite reduction rate over the first 24 hours following administration of OZ439, tolerability and exposure.


Sponsor: Medicines for Malaria Venture

Current Primary Outcome: Derived Parasite Reduction Rate at 24 Hours (PPR24) [ Time Frame: 24 hours after study drug administration ]

PRR24 is the log10 change in parasitemia over 24 hours estimated from a regression model fit separately for each patient. The relationship between parasite counts and time was analyzed by fitting a variable lag phase, then a linear decline to the natural log of parasite count versus time relationship. The slope of this log linear relationship is the primary end-point.

The time points chosen for the regression are those that yield the highest degree of significance when assessing the regression when the number of time points are greater than or equal to 3. No extrapolation was performed.



Original Primary Outcome: Derived parasite reduction rate (PRR) at 24 hours [ Time Frame: 24 h after study drug adminstration ]

• Parasite reduction ratio at 24 hours after study drug administration estimated separately for each patient from a regression model.The relationship between parasite counts and time will be analysed by fitting a variable lag phase then a linear decline to the Natural log of parasite count versus time relationship. The slope of this log linear relationship is the primary end-point, and all secondary variables related to parasite reduction will be derived from this best fit.


Current Secondary Outcome:

Original Secondary Outcome:

Information By: Medicines for Malaria Venture

Dates:
Date Received: October 1, 2010
Date Started: October 2010
Date Completion:
Last Updated: November 17, 2014
Last Verified: November 2014