Weekly Dosing of Malarone ® for Prevention of Malaria (MALWEEK)

October 29, 2013 updated by: U.S. Army Medical Research and Development Command

Pilot Evaluation of Weekly Dosing of Atovaquone/Proguanil (Malarone ®) for Malaria Chemoprophylaxis

The purpose of this study is to determine whether Malarone ®, which is a drug approved to prevent malaria when taken daily, will still effectively prevent malaria if taken weekly.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In this study, two groups of volunteers will be exposed to malaria through the bites of infected mosquitoes. In one group, volunteers will be randomly assigned to one of 5 arms. Each of these arms will receive a different dose of Malarone®, a drug known to prevent malaria when taken daily. Each of these doses will be lower than the maximum approved dose of this medicine. The other group will not be treated with any drug that could prevent symptoms or infection.

After exposure, both groups will be monitored for a period of approximately 3 months to see if they develop symptoms of malaria. Any subjects who do so will be treated with appropriate medications. Subjects in both groups will have their blood checked regularly during this period for the presence of malaria parasites. At the completion of the study, results will be analyzed to determine whether any of the doses of Malarone might effectively prevent malaria if taken weekly rather than daily.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Silver Spring, Maryland, United States, 20910
        • Walter Reed Army Institute of Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 48 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • A male or non-pregnant, non-lactating female 18 to 50 years of age (inclusive) at the time of screening
  • Free of clinically significant health problems
  • Baseline ECG before entering into the study
  • Available to participate for duration of study (approximately 4 months, not including screening period)
  • If the participant is female, not pregnant or lactating and willing to use contraception to prevent pregnancy
  • BMI between 19 and 30

Exclusion Criteria:

  • History of malaria or travel to a malarious country within the previous 12 months
  • History of participation in a study in which potential exposure to malaria or vaccination against malaria occurred.
  • Planned travel to malarious areas during the study period.
  • History of malaria chemoprophylaxis within 60 days prior to time of study entry.
  • Chronic use of antibiotics with anti-malarial effects
  • Chronic use (defined as more than 14 days)of immunosuppressants or other immune-modifying drugs within six months of study entry.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination, ECG or laboratory screening tests
  • Significant unexplained anemia
  • History of sickle cell disease or sickle cell trait
  • Seropositive for hepatitis B or hepatitis C
  • History of splenectomy
  • Pregnant or lactating female, or female who intends to become pregnant during the study
  • Suspected or known current alcohol abuse as defined by the American Psychiatric Association in DSM IV
  • History of a neuropsychiatric disorder (anxiety, depression, psychosis, schizophrenia)
  • Chronic or active illicit and/or intravenous drug use
  • History of allergy to atovaquone, proguanil or chloroquine
  • History of psoriasis
  • Concurrent participation in other research studies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug

5 groups, each group receiving Malarone tablet(s) (250/100mg)prior to challenge.

Group 1 - 1 tablet 1 day before challenge Group 2 - 1 tablet 4 days before challenge Group 3 - 1 tablet 7 days before challenge Group 4 - 2 tablets 7 days before challenge Group 5 - 4 tablets 7 days before challenge
Drug: Atovaquone Proguanil
Volunteers will receive doses of atovaquone/proguanil (Malarone) or matching sugar pills.
Other Names:
  • Malarone
  • Atovaquone
  • Malaria
  • Prophylaxis
  • Challenge
Other: Procedure - malaria challenge
2) Procedure- Malaria Challenge- Volunteers will be exposed to bites of infectious mosquitoes with the intention of causing malaria infection. Volunteers infected with malaria will undergo approved treatments for malaria.
Other Names:
  • Malarone
  • Atovaquone
  • Malaria
  • Prophylaxis
  • Challenge
Placebo Comparator: Control -no prophylaxis
Other: Procedure - malaria challenge
2) Procedure- Malaria Challenge- Volunteers will be exposed to bites of infectious mosquitoes with the intention of causing malaria infection. Volunteers infected with malaria will undergo approved treatments for malaria.
Other Names:
  • Malarone
  • Atovaquone
  • Malaria
  • Prophylaxis
  • Challenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prophylactic Efficacy of 3 Different Doses of Atovaquone/Proguanil (Malarone@) Given 1 Week Before Infectious Sporozoite Challenge Using the P. Falciparum Human Challenge Model.
Time Frame: Days 6-20
Number of participants with prophylactic efficacy was determined by the absence of cases of malaria parasitemia, defined as microscopically detectable parasitemia by Giemsa-stained thick smears, in those receiving any dose of Malarone as compared to the control (no treatment) group
Days 6-20

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measured Concentrations of Plasma Atovaquone With Determinations of T1/2.
Time Frame: 7, 6, 5, and 1 day prior to challenge; on the day of the challenge; 1, 4, 5, 6, 7, 8, 10and 14 days after the challenge; and on the day parasitemia develops.,
Plasma concentrations (ng/ml) were used to determine the elimination half life (t1/2) of atovaquone (days).
7, 6, 5, and 1 day prior to challenge; on the day of the challenge; 1, 4, 5, 6, 7, 8, 10and 14 days after the challenge; and on the day parasitemia develops.,
Measured Concentrations of Plasma Atovaquone With Determinations of Area Under the Curve
Time Frame: 7, 6, 5, and 1 day prior to challenge; on the day of the challenge; 1, 4, 5, 6, 7, 8, 10and 14 days after the challenge; and on the day parasitemia develops.,
Plasma concentrations were used to determine the pharmacokinetic curves with determinations of area under the curve (AUC).The smallest AUC Day 0-6.5 associated with protection from detectable parasitemia, and the highest AUC Day 0-6.5 observed in any cases of malaria (prophylactic failures) were to be reported.
7, 6, 5, and 1 day prior to challenge; on the day of the challenge; 1, 4, 5, 6, 7, 8, 10and 14 days after the challenge; and on the day parasitemia develops.,

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

U.S. Army Medical Research and Development Command

Investigators

  • Principal Investigator: Gregory Deye, MD, Walter Reed Army Institute of Research (WRAIR)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

September 24, 2009

First Submitted That Met QC Criteria

September 24, 2009

First Posted (Estimate)

September 25, 2009

Study Record Updates

Last Update Posted (Estimate)

November 25, 2013

Last Update Submitted That Met QC Criteria

October 29, 2013

Last Verified

October 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WRAIR 1583
  • HSRRB # A-15648 (Other Identifier: USAMRMC)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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