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

Primary Purpose

Malaria

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Atovaquone Proguanil

Procedure - malaria challenge

About this trial

This is an interventional prevention trial for Malaria focused on measuring Malaria, Prophylaxis, Atovaquone, Malarone, Challenge

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Walter Reed Army Institute of Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Drug

Control -no prophylaxis

Arm Description

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

Outcomes

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.

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.

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

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.

Full Information

NCT ID

NCT00984256

First Posted

September 24, 2009

Last Updated

October 29, 2013

Sponsor

U.S. Army Medical Research and Development Command

1. Study Identification

Unique Protocol Identification Number

NCT00984256

Brief Title

Weekly Dosing of Malarone ® for Prevention of Malaria

Acronym

MALWEEK

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2013

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

April 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

U.S. Army Medical Research and Development Command

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malaria

Keywords

Malaria, Prophylaxis, Atovaquone, Malarone, Challenge

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

35 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Drug

Arm Type

Experimental

Arm Description

Arm Title

Control -no prophylaxis

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Atovaquone Proguanil

Other Intervention Name(s)

Malaria, Prophylaxis, Atovaquone, Malarone, Challenge

Intervention Description

Volunteers will receive doses of atovaquone/proguanil (Malarone) or matching sugar pills.

Intervention Type

Other

Intervention Name(s)

Procedure - malaria challenge

Other Intervention Name(s)

Malaria, Prophylaxis, Atovaquone, Malarone, Challenge

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Days 6-20

Secondary Outcome Measure Information:

Title

Measured Concentrations of Plasma Atovaquone With Determinations of T1/2.

Description

Plasma concentrations (ng/ml) were used to determine the elimination half life (t1/2) of atovaquone (days).

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.,

Title

Measured Concentrations of Plasma Atovaquone With Determinations of Area Under the Curve

Description

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.,

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gregory Deye, MD

Organizational Affiliation

Walter Reed Army Institute of Research (WRAIR)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Walter Reed Army Institute of Research

City

Silver Spring

State/Province

Maryland

ZIP/Postal Code

20910

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22052893

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.

Results Reference

result

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Weekly Dosing of Malarone ® for Prevention of Malaria

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