Safety and Efficacy Study of IV Artesunate to Treat Malaria

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

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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Drug: Artesunate; Drug: Malarone

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Kenya
  • New Nyanza
    • Kisumu, New Nyanza, Kenya
      • New Nyanza Provincial Hospital

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: quinidine; Drug: Malarone; (proguanil/atovaquone) follow-on therapy (4 tablets once daily for three days); Other Names: atovaquone and proguanil hydrochloride

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: Military Infectious Diseases Research Program (MIDRP)
• Investigators: Principal Investigator: Shon A Remich, MD, Walter Reed Army Institute of Research (WRAIR)

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: March 1, 2006
• First Submitted That Met QC Criteria: March 1, 2006
• First Posted (Estimate): March 2, 2006

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Uncomplicated Malaria; GMP artesunate
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Membrane Transport Modulators; Cytochrome P-450 Enzyme Inhibitors; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Adrenergic alpha-Antagonists; Schistosomicides; Antiplatyhelmintic Agents; Atovaquone; Proguanil; Artesunate; Quinidine; Atovaquone, proguanil drug combination
• Other Study ID Numbers: WRAIR 1168; KEMRI 917 (Other Identifier: IRB); HSRRB A-13331 (Other Identifier: IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No