Safety and Efficacy Study of IV Artesunate to Treat Malaria

Study Overview
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Brief Summary
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The purpose of this study is to determine how GMP IV Artesunate is metabolized and cleared by individuals with uncomplicated malaria infection and to determine how fast it eliminates malaria infection from the body.

Detailed Description
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This is an unblinded non-randomized phase II pharmacokinetic study of a new GMP formulation of intravenous artesunate. Artesunate has been used throughout Asia and Africa for many years. Its overall efficacy associated with the ability to lower parasitemia is well established. To date, pharmacokinetic studies have not been done in Africa using GMP (Good Manufacturing Practices)-produced drug. The objective of this study is to show that GMP IV artesunate rapidly clears parasites in Adult Kenyan populations with malaria and that the pharmacokinetic profile of the drug approximates other populations of adults tested (Asians and North Americans).

Official Title
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A Phase II, Open Label, Study of the Safety, Tolerability, Efficacy and Pharmacokinetics of Intravenous Artesunate in Adults With Uncomplicated Malaria

Conditions
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Malaria

Intervention / Treatment
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* Drug: Artesunate
* Drug: Malarone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male & non-pregnant females, 18-65 years Fever, defined as >37.5ºC, during the current illness, or history (within the last 48 hours) of fever. Diagnosis of falciparum malaria, greater than or equal to 200 parasites/uL Able to communicate well with the investigator and to comply with the requirements of the entire study. Willing to be admitted for the period of drug administration and/or to follow up (return to hospital) Provision of the written informed consent to participate as shown by a signature on the informed consent form. Exclusion Criteria: Administration of any investigational drug in the period 0 to 16 weeks before entry to the study. The use of any medication during the period 0 to 14 days (prescribed drugs) or 0 to 5 days (OTC) before entry to the study (including herbal or dietary supplements), except those deemed by the principal investigator / clinical investigator not to interfere with the outcome of the study. Existence of any surgical or medical condition that, in the judgment of the clinical investigator, might interfere with the distribution, metabolism or excretion of the drug. History of serious adverse reaction or hypersensitivity to study drug or follow on treatment. Mixed malaria infection (malaria other than falciparum malaria mono-infection as detected by screening blood smear) Severe falciparum malaria (as defined by the WHO; Attachment 1). Donation or loss of greater than 400 ml of blood in the period 0 to 12 weeks before entry to the study, Transfusion of blood within past 30 days. Refusal to prevent pregnancy during the 14 days of the trial Pregnancy as defined clinically or by a positive urine BHCG at the time of screening, or nursing mothers. Laboratory evidence or history of significant cardiovascular, liver or renal functional abnormality, which in the opinion of the investigator would place them at increased risk. Specifically, the following will serve as exclusionary lab values: Creatinine >1.4 x ULN (>2.0 mg/dL) Glucose <LLN (65mg/dL) AST, ALT >3x ULN (120 U/L)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artesunate and Malarone<br>Subject are given intravenous Artesunate once a day for 3 days. Following completion of Artesunate treatment, all subjects received Malarone follow-on therapy to ensure parasitologic cure. | Drug: Artesunate<br>* Intravenous Artesunate (2.4 mg/kg) once a day for three days<br>* Other names: quinidine;Drug: Malarone<br>* (proguanil/atovaquone) follow-on therapy (4 tablets once daily for three days)<br>* Other names: atovaquone and proguanil hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Percentage of Parasites Detected at 48 Hours | Change in Percentage of Parasites Detected at 48 Hours. With positive numbers to represent increases and negative numbers to represent decreases | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Parasite Clearance | The target variable is detection (percentage) of asexual stage parasites of Plasmodium falciparum malaria in bloodstream by Giemsa - stained microscopy of thick and thin blood smears | 24 and 48 hours post dose | 
| Number of Subjects With Fever Clearance | Temperature is measured by oral digital thermometers, and fever clearance time is defined as the first time with resolution of fever (<37.5C) sustained for 24 hours | Within 48 hours post dose | 
| Safety - Severity of Adverse Events | Determine the safety (defined as severity of AE's using the Common Toxicity Criteria) | up to 14 days | 
| Safety - Adverse Events Relationship to Study Drug | Determine the safety (defined as relationship to study drug of AE's and SAE's) | up to 14 days | 
| Safety - Severity of Serious Adverse Events (SAE's) | Determine the safety (defined as severity of SAE's using the Common Toxicity Criteria) | up to 14 days | 
| Safety - Serious Adverse Event (SAE) Relationship to Study Drug | Determine the safety (defined as relationship to study drug of SAE's) | Up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uncomplicated Malaria, GMP artesunate