Weekly Dosing of Malarone ® for Prevention of Malaria

Phase 2

Completed

Interventions: Drug: Atovaquone Proguanil
Other: Procedure - malaria challenge

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Drug	Atovaquone Proguanil	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	Procedure - malaria challenge	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
Control -no prophylaxis	Procedure - malaria challenge	-

Primary Outcome Measures

Name	Time	Method
Prophylactic Efficacy of 3 Different Doses of Atovaquone/Proguanil (Malarone@) Given 1 Week Before Infectious Sporozoite Challenge Using the P. Falciparum Human Challenge Model.	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

Secondary Outcome Measures

Name	Time	Method
Measured Concentrations of Plasma Atovaquone With Determinations of T1/2.	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).
Measured Concentrations of Plasma Atovaquone With Determinations of Area Under the Curve	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.