Clinical trial NCT00298610: Safety and Efficacy Study of IV Artesunate to Treat Malaria
Official title: A Phase II, Open Label, Study of the Safety, Tolerability, Efficacy and Pharmacokinetics of Intravenous Artesunate in Adults With Uncomplicated Malaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: Uncomplicated Malaria
GMP artesunate
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: Military Infectious Diseases Research Program (MIDRP)
First posted: 2006-03-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Percentage of Parasites Detected at 48 Hours
timeFrame: 48 hours
Secondary outcomes:
measure: Percentage of Parasite Clearance
timeFrame: 24 and 48 hours post dose
measure: Number of Subjects With Fever Clearance
timeFrame: Within 48 hours post dose
measure: Safety - Severity of Adverse Events
timeFrame: up to 14 days
measure: Safety - Adverse Events Relationship to Study Drug
timeFrame: up to 14 days
measure: Safety - Severity of Serious Adverse Events (SAE's)
timeFrame: up to 14 days
measure: Safety - Serious Adverse Event (SAE) Relationship to Study Drug
timeFrame: Up to 14 days
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: New Nyanza Provincial Hospital
state: New Nyanza
Study officials:
affiliation: Walter Reed Army Institute of Research (WRAIR)
name: Shon A Remich, MD
role: PRINCIPAL_INVESTIGATOR
References: