Clinical trial NCT00984256: Weekly Dosing of Malarone ® for Prevention of Malaria
Official title: Pilot Evaluation of Weekly Dosing of Atovaquone/Proguanil (Malarone ®) for Malaria Chemoprophylaxis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: Malaria
Prophylaxis
Atovaquone
Malarone
Challenge
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
First posted: 2009-09-25
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Prophylactic Efficacy of 3 Different Doses of Atovaquone/Proguanil (Malarone@) Given 1 Week Before Infectious Sporozoite Challenge Using the P. Falciparum Human Challenge Model.
timeFrame: Days 6-20
Secondary outcomes:
measure: Measured Concentrations of Plasma Atovaquone With Determinations of T1/2.
timeFrame: 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.,
measure: Measured Concentrations of Plasma Atovaquone With Determinations of Area Under the Curve
timeFrame: 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.,
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: Walter Reed Army Institute of Research
state: Maryland
Study officials:
affiliation: Walter Reed Army Institute of Research (WRAIR)
name: Gregory Deye, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Deye GA, Miller RS, Miller L, Salas CJ, Tosh D, Macareo L, Smith BL, Fracisco S, Clemens EG, Murphy J, Sousa JC, Dumler JS, Magill AJ. Prolonged protection provided by a single dose of atovaquone-proguanil for the chemoprophylaxis of Plasmodium falciparum malaria in a human challenge model. Clin Infect Dis. 2012 Jan 15;54(2):232-9. doi: 10.1093/cid/cir770. Epub 2011 Nov 3.