Safety and Efficacy Study of IV Artesunate to Treat Malaria

• ClinicalTrials.gov Identifier: NCT00298610
• Recruitment Status: Completed
• First Posted: March 2, 2006
• Results First Posted: March 22, 2017
• Last Update Posted: October 1, 2019
• Sponsor: U.S. Army Medical Research and Development Command
• Collaborator: Military Infectious Diseases Research Program (MIDRP)
• Information provided by (Responsible Party): U.S. Army Medical Research and Development Command

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malaria	Drug: Artesunate; Drug: Malarone	Phase 2

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open Label, Study of the Safety, Tolerability, Efficacy and Pharmacokinetics of Intravenous Artesunate in Adults With Uncomplicated Malaria
• Study Start Date: March 2006
• Actual Primary Completion Date: October 2007
• Actual Study Completion Date: October 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: Artesunate and Malarone; 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; Intravenous Artesunate (2.4 mg/kg) once a day for three days; Other Name: quinidine; Drug: Malarone; (proguanil/atovaquone) follow-on therapy (4 tablets once daily for three days); Other Name: atovaquone and proguanil hydrochloride

Outcome Measures

Primary Outcome Measures :

1. Change in Percentage of Parasites Detected at 48 Hours [ Time Frame: 48 hours ]
   Change in Percentage of Parasites Detected at 48 Hours. With positive numbers to represent increases and negative numbers to represent decreases

Secondary Outcome Measures :

1. Percentage of Parasite Clearance [ Time Frame: 24 and 48 hours post dose ]
   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
2. Number of Subjects With Fever Clearance [ Time Frame: Within 48 hours post dose ]
   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
3. Safety - Severity of Adverse Events [ Time Frame: up to 14 days ]
   Determine the safety (defined as severity of AE's using the Common Toxicity Criteria)
4. Safety - Adverse Events Relationship to Study Drug [ Time Frame: up to 14 days ]
   Determine the safety (defined as relationship to study drug of AE's and SAE's)
5. Safety - Severity of Serious Adverse Events (SAE's) [ Time Frame: up to 14 days ]
   Determine the safety (defined as severity of SAE's using the Common Toxicity Criteria)
6. Safety - Serious Adverse Event (SAE) Relationship to Study Drug [ Time Frame: Up to 14 days ]
   Determine the safety (defined as relationship to study drug of SAE's)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

Kenya

New Nyanza Provincial Hospital

Kisumu, New Nyanza, Kenya

Sponsors and Collaborators

U.S. Army Medical Research and Development Command

Military Infectious Diseases Research Program (MIDRP)

Investigators

• Principal Investigator: Shon A Remich, MD; Walter Reed Army Institute of Research (WRAIR)

More Information

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT00298610
• Other Study ID Numbers: WRAIR 1168; KEMRI 917 ( Other Identifier: IRB ); HSRRB A-13331 ( Other Identifier: IRB )
• First Posted: March 2, 2006
• Results First Posted: March 22, 2017
• Last Update Posted: October 1, 2019
• Last Verified: November 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by U.S. Army Medical Research and Development Command:

Uncomplicated Malaria; GMP artesunate

Additional relevant MeSH terms:

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Artesunate; Atovaquone; Proguanil; Quinidine; Atovaquone, proguanil drug combination; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Schistosomicides; Antiplatyhelmintic Agents; Anthelmintics; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Muscarinic Antagonists; Cholinergic Antagonists