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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT00984256
First received: September 24, 2009
Last updated: October 29, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: Atovaquone Proguanil
Other: Procedure - malaria challenge
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Pilot Evaluation of Weekly Dosing of Atovaquone/Proguanil (Malarone ®) for Malaria Chemoprophylaxis

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 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., ] [ Designated as safety issue: No ]
    Plasma concentrations (ng/ml) were used to determine the elimination half life (t1/2) of atovaquone (days).

  • 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., ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: September 2009
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Malaria
  • Prophylaxis
  • Atovaquone
  • Malarone
  • 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:
  • Malaria
  • Prophylaxis
  • Atovaquone
  • Malarone
  • 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:
  • Malaria
  • Prophylaxis
  • Atovaquone
  • Malarone
  • Challenge

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00984256

Locations
United States, Maryland
Walter Reed Army Institute of Research
Silver Spring, Maryland, United States, 20910
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Gregory Deye, MD Walter Reed Army Institute of Research (WRAIR)
  More Information

Additional Information:
Publications:
Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT00984256     History of Changes
Other Study ID Numbers: WRAIR 1583, HSRRB # A-15648
Study First Received: September 24, 2009
Results First Received: September 4, 2012
Last Updated: October 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
Malaria
Prophylaxis
Atovaquone
Malarone
Challenge

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Proguanil
Atovaquone
Atovaquone, proguanil drug combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014