Weekly Dosing of Malarone ® for Prevention of Malaria

Malaria Clinical Trial

— MALWEEK  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00984256
• Other study ID #: WRAIR 1583
• Secondary ID: HSRRB # A-15648
• Status: Completed
• Phase: Phase 2
• First received: September 24, 2009
• Last updated: October 29, 2013
• Start date: September 2009
• Est. completion date: April 2010

Study information

• Verified date: October 2013
• Source: U.S. Army Medical Research and Materiel Command
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Atovaquone Proguanil
Volunteers will receive doses of atovaquone/proguanil (Malarone) or matching sugar pills.

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.

Locations

Country	Name	City	State
United States	Walter Reed Army Institute of Research	Silver Spring	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
U.S. Army Medical Research and Materiel Command

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prophylactic Efficacy of 3 Different Doses of Atovaquone/Proguanil (Malarone@) Given 1 Week Before Infectious Sporozoite Challenge Using the P. Falciparum Human Challenge Model.	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	No
Secondary	Measured Concentrations of Plasma Atovaquone With Determinations of T1/2.	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.,	No
Secondary	Measured Concentrations of Plasma Atovaquone With Determinations of Area Under the Curve	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.,	No

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