Phase II Dose Ranging Study of Artesunate - Full Text View

Sponsors and Collaborators:	U.S. Army Office of the Surgeon General Military Infectious Diseases Research Program (MIDRP) U.S. Army Medical Research and Materiel Command
Information provided by:	Walter Reed Army Institute of Research (WRAIR)
ClinicalTrials.gov Identifier:	NCT00459615

Purpose

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.

Condition	Intervention	Phase
Falciparum Malaria Uncomplicated Malaria	Drug: Artesunate for Injection	Phase II

MedlinePlus related topics: Malaria

Drug Information available for: Artesunate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase II, Randomized, Open-Label, Dose-Ranging Study of Intravenous Artesunate Therapy for the Treatment of Acute, Uncomplicated Plasmodium Falciparum Malaria.

Further study details as provided by Walter Reed Army Institute of Research (WRAIR):

Primary Outcome Measures:

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:

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.

Estimated Enrollment:	120
Study Start Date:	April 2007
Study Completion Date:	January 2008
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	12 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459615

Locations

Kenya, Nyanza
New Nyanza Provincial Hospital
Kisumu, Nyanza, Kenya
Thailand, Kanchanaburi
Kwai River Christian Hospital
Sangkhlaburi, Kanchanaburi, Thailand

Sponsors and Collaborators

U.S. Army Office of the Surgeon General

Military Infectious Diseases Research Program (MIDRP)

U.S. Army Medical Research and Materiel Command

Investigators

Principal Investigator:	Mark Polhemus, MD	USAMRU-K
Principal Investigator:	Bryan Smith, MD	Armed Forces Research Institute of Medical Sciences

More Information

Related Info This link exits the ClinicalTrials.gov site

Study ID Numbers:	WRAIR 1263, HSRRB Protocol Log#A-13912a,b
Study First Received:	April 10, 2007
Last Updated:	September 23, 2008
ClinicalTrials.gov Identifier:	NCT00459615
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Artesunate
Protozoan Infections
Parasitic Diseases
Malaria
Malaria, Falciparum

Additional relevant MeSH terms:

Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents

Coccidiosis
Therapeutic Uses
Amebicides
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009