Phase II Dose Ranging Study of Artesunate
The purpose of this study is to compare four regimens using US FDA GMP intravenous artesunate for the treatment of uncomplicated Plasmodium falciparum malaria to identify the most effective treatment regimen as determined by rapidity of parasite clearance by microscopy.
Drug: Artesunate for Injection
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
|Official Title:||A Phase II, Randomized, Open-Label, Dose-Ranging Study of Intravenous Artesunate Therapy for the Treatment of Acute, Uncomplicated Plasmodium Falciparum Malaria.|
- The primary endpoint for this pharmacodynamic study is clearance of falciparum parasites from the blood.
- Reference microscopic interpretation of Giemsa-stained thick and thin blood smears for malaria will serve as the diagnostic method of parasitemia detection.
- Parasite clearance will be quantified using a discrete variable denoting efficacy to clear at least 90% of asexual parasites from the peripheral blood by 48 hours after administration of IV artesunate
- Additional measures of parasite clearance will also be assessed.
- A continuous variable of time to parasite reduction milestones:
- parasite clearance time (PCT90 and PCT100), and parasite reduction ratios (PRR12h and PRR24h) at defined time points , and
- A continuous variable of area under the curve (AUC) of quantifiable parasitemia
- Tolerability of the treatment regimens will also be assessed throughout the study through use of evaluation for adverse events and safety laboratories to include hematology and chemistry tests.
|Study Start Date:||April 2007|
|Study Completion Date:||January 2008|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
To compare the efficacy and tolerability of intravenous artesunate for the initial treatment of uncomplicated Plasmodium falciparum malaria at doses that bracket anticipated clinical doses (2.4 mg/kg once daily for 3 days; or 2.4 mg/kg initially, at 12 hours on Day 0, and then daily on Day 1 and 2) and thereby establish the safest, highly efficacious dosing regimen for use in future clinical trials.
|New Nyanza Provincial Hospital|
|Kisumu, Nyanza, Kenya|
|Kwai River Christian Hospital|
|Sangkhlaburi, Kanchanaburi, Thailand|
|Principal Investigator:||Mark Polhemus, MD||USAMRU-K|
|Principal Investigator:||Bryan Smith, MD||Armed Forces Research Institute of Medical Sciences, Thailand|