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Phase II Dose Ranging Study of Artesunate

Primary Purpose

Falciparum Malaria, Uncomplicated Malaria

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Artesunate for Injection

About this trial

This is an interventional treatment trial for Falciparum Malaria

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

New Nyanza Provincial Hospital
Kwai River Christian Hospital

Outcomes

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.

Full Information

NCT ID

NCT00459615

First Posted

April 10, 2007

Last Updated

September 23, 2008

Sponsor

U.S. Army Office of the Surgeon General

Collaborators

Military Infectious Diseases Research Program (MIDRP), U.S. Army Medical Research and Development Command

1. Study Identification

Unique Protocol Identification Number

NCT00459615

Brief Title

Phase II Dose Ranging Study of Artesunate

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2008

Overall Recruitment Status

Completed

Study Start Date

April 2007 (undefined)

Primary Completion Date

December 2007 (Actual)

Study Completion Date

January 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

U.S. Army Office of the Surgeon General

Collaborators

Military Infectious Diseases Research Program (MIDRP), U.S. Army Medical Research and Development Command

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Falciparum Malaria, Uncomplicated Malaria

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Single

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Artesunate for Injection

Primary Outcome Measure Information:

Title

The primary endpoint for this pharmacodynamic study is clearance of falciparum parasites from the blood.

Title

Reference microscopic interpretation of Giemsa-stained thick and thin blood smears for malaria will serve as the diagnostic method of parasitemia detection.

Title

Secondary Outcome Measure Information:

Title

Additional measures of parasite clearance will also be assessed.

Title

A continuous variable of time to parasite reduction milestones:

Title

parasite clearance time (PCT90 and PCT100), and parasite reduction ratios (PRR12h and PRR24h) at defined time points , and

Title

A continuous variable of area under the curve (AUC) of quantifiable parasitemia

Title

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Polhemus, MD

Organizational Affiliation

USAMRU-K

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Bryan Smith, MD

Organizational Affiliation

Armed Forces Research Institute of Medical Sciences, Thailand

Official's Role

Principal Investigator

Facility Information:

Facility Name

New Nyanza Provincial Hospital

City

Kisumu

State/Province

Nyanza

Country

Kenya

Facility Name

Kwai River Christian Hospital

City

Sangkhlaburi

State/Province

Kanchanaburi

Country

Thailand

12. IPD Sharing Statement

Links:

URL

http://usamrukenya.org

Description

Related Info

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Phase II Dose Ranging Study of Artesunate

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