MalariaPhase 2MALWEEKNCT00984256
Weekly Dosing of Malarone ® for Prevention of Malaria
A Phase 2 study testing Atovaquone Proguanil and Procedure - malaria challenge in people with Malaria, run by U.S. Army Medical Research and Development Command at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Atovaquone Proguanil and Procedure - malaria challenge
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2009to Apr 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Walter Reed Army Institute of Research
Silver Spring, Maryland, 20910
About this study
Official title: Pilot Evaluation of Weekly Dosing of Atovaquone/Proguanil (Malarone ®) for Malaria Chemoprophylaxis
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.
Read the 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.
- Conditions
- Malaria
- Being tested
- Atovaquone Proguanil, Procedure - malaria challenge
- Keywords
- Malaria, Prophylaxis, Atovaquone, Malarone, Challenge
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atovaquone ProguanilDrug
Also called Malaria, Prophylaxis, Atovaquone, Malarone
Volunteers will receive doses of atovaquone/proguanil (Malarone) or matching sugar pills.
Procedure - malaria challengeOther
Also called Malaria, Prophylaxis, Atovaquone, Malarone
- 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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Atovaquone Proguanil; Other: Procedure - malaria challenge |
| Control -no prophylaxis | Placebo comparator | Not described Receives: Other: Procedure - malaria challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Days 6-20
Secondary outcomes (2)
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: 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
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.
Measured: 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.,
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionApr 2010
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Gregory Deye, MD, Principal investigator, Walter Reed Army Institute of Research (WRAIR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00984256
- Sponsor's protocol ID
- WRAIR 1583
- Other IDs
- HSRRB # A-15648
- Acronym
- MALWEEK
- Status last verified
- Oct 2013
- First submitted
- 24 Sep 2009
- Last updated
- 25 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 22052893
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Evaluation of Weekly Dosing of Atovaquone/Proguanil (Malarone ®) for Malaria Chemoprophylaxis
- ClinicalTrials.gov ID
- NCT00984256
- Acronym / sponsor ID
- MALWEEK / WRAIR 1583
- Conditions
- Malaria
- Keywords
- Malaria, Prophylaxis, Atovaquone, Malarone, Challenge
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Study start
- Sep 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 25 Sep 2009 (estimated)
- Results
- Posted 25 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Drug | Experimental | Drug: Atovaquone Proguanil, Other: Procedure - malaria challenge5 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 | Placebo comparator | Other: Procedure - malaria challenge |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atovaquone ProguanilAlso: Malaria, Prophylaxis, Atovaquone, MalaroneVolunteers will receive doses of atovaquone/proguanil (Malarone) or matching sugar pills. | Drug | Drug |
| Procedure - malaria challengeAlso: Malaria, Prophylaxis, Atovaquone, Malarone2) 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. | Other | Control -no prophylaxis, Drug |
Primary outcome
Prophylactic Efficacy of 3 Different Doses of Atovaquone/Proguanil (Malarone@) Given 1 Week Before Infectious Sporozoite Challenge Using the P. Falciparum Human Challenge Model.
Time frame: 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
2 secondary outcomes
Measured Concentrations of Plasma Atovaquone With Determinations of T1/2.
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.,
Measured Concentrations of Plasma Atovaquone With Determinations of Area Under the Curve
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.,
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22052893Deye 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory Deye, MD principal investigator
Walter Reed Army Institute of Research (WRAIR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atovaquone Proguanil and Procedure - malaria challenge in people with Malaria, run by U.S. Army Medical Research and Development Command at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Days 6-20). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00984256, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2013.