Phase 2 Efficacy Study of Primaquine and Methylene Blue

January 9, 2017 updated by: University of California, San Francisco

Efficacy, Safety, and Pharmacokinetics of Sulphadoxine-pyrimethamine-amodiaquine (SP-AQ), SP-AQ Plus Primaquine, Dihydroartemisinin-piperaquine (DP), DP Plus Methylene Blue for Preventing Transmission of P. Falciparum Gametocytes in Mali

The purpose of this study is to determine the most efficacious transmission blocking drug regimen for seasonal malaria chemoprophylaxis in Mali. The primary outcome measure will be the proportion of mosquitoes infected pre and post-treatment, assessed through membrane feeding and measured by oocyst prevalence in mosquitoes dissected on day 7 post feed. Primary endpoint will be a within group comparison between the mean of the pretreatment infectivity (Day 0) and infectivity at 7 days post first dose.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Protocol will be shared on request.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mali
      • Bamako, Mali
        • Malaria Research and Training Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

5 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Glucose-6-phosphate dehydrogenase (G6PD) normal defined by CareStart™ G6PD rapid diagnostic test (RDT) or the OSMMR2000 G6PD semi-qualitative test
  • Absence of symptomatic falciparum malaria, defined by fever upon enrollment
  • Presence of P. falciparum gametocytes on thick blood film at a density >30 gametocytes/µL (i.e. ≥2 gametocytes recorded in the thick film against 500 white blood cells)
  • No allergies to study drugs
  • No self-reported use of antimalarial drugs over the past 7 days (as reported by the participant)
  • Hemoglobin ≥ 10 g/dL
  • Individuals weighing <80 kg
  • No evidence of severe or chronic disease
  • Written, informed consent

Exclusion Criteria:

  • Age < 5 years or > 50 years
  • Female gender
  • Blood thick film negative for sexual stages of malaria
  • Previous reaction to study drugs/known allergy to study drugs
  • Signs of severe malaria, including hyperparasitemia, defined as asexual parasitemia > 100,000 parasites / µL)
  • Signs of acute or chronic illness, including hepatitis
  • Use of other medications (with the exception of paracetamol and/or aspirin)
  • Consent not given

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: SP-AQ only
Subjects will receive sulphadoxine-pyrimethamine (SP) as single dose and administered in combination with amodiaquine (AQ), which will be given once daily for 3 days.
Drug: Sulphadoxine-pyrimethamine
Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine. Doses will be administered by weight.
Other Names:
  • Fansidar
Drug: Amodiaquine
Amodiaquine will be administered once daily for 3 days, following weight-based dosing of 150 mg tablets.
Experimental: SP-AQ plus PQ
Participants in this arm will receive SP-AQ in combination with a single low dose of primaquine at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
Drug: Sulphadoxine-pyrimethamine
Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine. Doses will be administered by weight.
Other Names:
  • Fansidar
Drug: Amodiaquine
Amodiaquine will be administered once daily for 3 days, following weight-based dosing of 150 mg tablets.
Drug: 0.25 mg/kg primaquine
Primaquine will be administered in an aqueous solution according to weight-based dosing.
Active Comparator: DP only
Participants in this arm will be treated with dihydroartemisinin-piperaquine (DP), which will be administered once a day for three days.
Drug: Dihydroartemisinin-piperaquine
160mg/20mg or 320mg/40mg of dihydroartemisinin/piperaquine tablets will be used to administer weight-based doses.
Other Names:
  • Eurartesim
Experimental: DP plus MB
Study participants in this arm will receive DP as described above combined with once-daily methylene blue (MB) for 3 days, at 15 mg/kg/day (45 mg/kg total over 3 days).
Drug: Methylene blue
Methylene blue will be given as minitablets in prepackaged sachets according to weight groups.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mosquito infectivity assessed through membrane feeding assays
Time Frame: 7 day
Infectivity will be measured by oocyst prevalence in dissected mosquitoes. Primary endpoint will be a comparison between mean of pretreatment infectivity (day 0) and infectivity at days 2 and 7 post first dose.
7 day

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Gametocyte prevalence, density, and sex ratio measured microscopically and by molecular methods.
Time Frame: 42 days
Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose.
42 days
Asexual parasite prevalence and density
Time Frame: 42 days
Asexual parasitemia will be evaluated by blood smear microscopy and confirmed by more sensitive, molecular methods. Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose.
42 days
Safety measurements including hemoglobin and signs of hemolysis
Time Frame: 42 days
The major safety endpoint is hemolysis. For this reason, hemoglobin and methemoglobin values will be measured before treatment, at baseline and on days 1, 2, 3, 7, 14, 28, and 42 post first dose. In addition, clinical review (including additional signs of hemolysis) will be assessed based on active and passive follow-up.
42 days
Peak plasma concentration (Cmax) of primaquine
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Area under the concentration curve (AUC) of primaquine.
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Elimination half life (t1/2) of primaquine
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Peak plasma concentration (Cmax) of methylene blue
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Area under the concentration curve (AUC) of methylene blue
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Elimination half life (t1/2) of methylene blue
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Peak plasma concentration (Cmax) of sulphadoxine-pyrimethamine
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Area under the concentration curve (AUC) of sulphadoxine-pyrimethamine
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Elimination half-life (t1/2) of sulphadoxine-pyrimethamine
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Peak plasma concentration (Cmax) of dihydroartemisinin-piperaquine
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Area under the concentration curve (AUC) of dihydroartemisinin-piperaquine
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Elimination half-life (t1/2) of dihydroartemisinin-piperaquine
Time Frame: 24 hours
Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
24 hours
Identification of cytochrome P450 (CYP) 2D6 and G6PD polymorphisms
Time Frame: 1 hour
CYP2D6 and G6PD genotyping will be performed using Thermo Fisher Scientific OpenArray Technology and Copy Number Variation (CNV) assays on the QuantStudio™ 12K Flex Real-Time PCR System.
1 hour

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Francisco

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
London School of Hygiene and Tropical Medicine
Radboud University Medical Center
Bill and Melinda Gates Foundation
Heidelberg University
Malaria Research and Training Center, Bamako, Mali

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Roland Gosling, MD, PhD, University of California, San Francisco
  • Principal Investigator: Alassane Dicko, MD, Malaria Research and Training Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 6, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 13, 2016

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 11, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UCSF CHR # 15-16839

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Data can be shared on request

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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