Phase II Dose Ranging Study of Artesunate

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II, Randomized, Open-Label, Dose-Ranging Study of Intravenous Artesunate Therapy for the Treatment of Acute, Uncomplicated Plasmodium Falciparum Malaria.

Conditions
-----------------
Falciparum Malaria, Uncomplicated Malaria

Intervention / Treatment
-----------------
* Drug: Artesunate for Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acute symptomatic Plasmodium falciparum malaria infection as determined by malaria smear with a parasite density of ≥ 5000 asexual parasites/mL Age: 5-65 year old males and females. Written informed consent must be obtained from adults age > 18 years. Parental consent will be obtained from children and adolescents, and subject assent will also be obtained from adolescents (age 12-17 years). Willing to stay hospitalized for 4 days for treatment and for 3 scheduled follow-up outpatient visits at Day 7, 14 and 28. Exclusion Criteria: Pregnant women (clinically or by positive urine β-HCG) and nursing mothers Clinical evidence of severe malaria (see Appendix B) Mixed malaria infection on admission by malaria smear A previous history of intolerance or hypersensitivity to the study drug artesunate or other artemisinin derivatives or Malarone. Efficacious malaria drug therapy administered in the past 30 days by history (i.e. quinine, mefloquine, lumefantrine and artemisinin derivatives) Previous participation in this trial or participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study. Laboratory evidence or a history of significant liver or renal functional abnormality. Anyone who has received a transfusion or any blood product within 30 days Unable and/or unlikely to comprehend and/or follow the protocol. Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Artesunate for Injection|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  |  |