A 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
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Derived parasite reduction rate (PRR) at 24 hours [ Time Frame: 24 h after study drug adminstration ] [ Designated as safety issue: No ]• 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.
|Study Start Date:||October 2010|
|Study Completion Date:||May 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
|Experimental: 800 mg OZ439 single dose||
po, single dose
|Experimental: 400 mg OZ439 p.o.||
po, single dose
|Experimental: 200mg OZ439 p.o.||
po, single dose
|Experimental: 1200 mg OZ439 po||
po, single dose
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. Established antimalarial therapy will be given earlier if a patient meets early treatment failure (ETF) defined as: 1) parasitaemia by 12 hours greater or equal to that at pre-dosing, regardless of temperature or 2) parasitaemia at 24 hours which has not fallen by >75% as compared to pre-dose regardless of temperature.
The primary endpoint will be the parasite reduction rate (PRR) slope. This is the slope of the log-linear portion of the loge parasitaemia versus time relationship. From this all other measures such as parasite reduction ratios will be derived (H24). Times to 50% and 90% reduction in parasitaemia will be derived from the best fit relationships.
A review of each individual study cohort (dose/species) will be conducted with the Principal Investigator and the Sponsor and a decision 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. If available data from the parallel cohort, discussion on how to progress will include both cohort findings and decision may include stopping with dose (de) escalation with one cohort and continuing with the other. The predominant consideration on dosing decisions will be that of patient safety.
Based on parasite reduction, the provision of established antimalarial therapy may be delayed beyond 36 hours and up to a maximum of 72 hours from the study drug dose, under continued 6 hourly (4 hourly up to 24 hours) monitoring parasitaemia. This will occur if the patient has achieved a symptomatic recovery but parasitaemia is still detectable at 36 hours.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01213966
|Faculty of Tropical Medicine, Mahidol University,|
|Bangkok, Thailand, 10400|
|Principal Investigator:||Sasithon Pukrittayakamee, MD||Mahidol University|