Weekly Dosing of Malarone ® for Prevention of Malaria

NCT00984256 | Completed Phase 2 Results

• 2 other identifiers: WRAIR 1583HSRRB # A-15648
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

Malaria; Prophylaxis; Atovaquone; Malarone; Challenge

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• 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.,

• 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.,

Study Arms (2)

Drug

EXPERIMENTAL

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; Other: Procedure - malaria challenge

Control -no prophylaxis

PLACEBO COMPARATOR

Other: Procedure - malaria challenge

Interventions

Atovaquone Proguanil DRUG

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

Also known as: Malaria, Prophylaxis, Atovaquone, Malarone, Challenge

Drug

Procedure - malaria challenge OTHER

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.

Also known as: Malaria, Prophylaxis, Atovaquone, Malarone, Challenge

Control -no prophylaxis; Drug

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead

Study Sites (1)

Walter Reed Army Institute of Research

Silver Spring, Maryland, 20910, United States

Location

Related 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 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.

  PMID: 22052893 RESULT

MeSH Terms

Conditions

Malaria

Interventions

atovaquone, proguanil drug combination; Atovaquone; Human Challenge Trials as Topic

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Naphthoquinones; Quinones; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Michelle Mathers
• Organization: US Army Medical Materiel Development Activity (USAMMDA)

Michelle.mathers@us.army.mil

301-619-8061

Study Officials

• Gregory Deye, MD

  Walter Reed Army Institute of Research (WRAIR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2009
• First Posted: September 25, 2009
• Study Start: September 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: November 25, 2013
• Results First Posted: November 25, 2013

Record last verified: 2013-10

Locations

US (1)