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

Detailed Description

Protocol will be shared on request.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • 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

      • 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

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
Intervention / Treatment
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.
Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine. Doses will be administered by weight.
Other Names:
  • Fansidar
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.
Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine. Doses will be administered by weight.
Other Names:
  • Fansidar
Amodiaquine will be administered once daily for 3 days, following weight-based dosing of 150 mg tablets.
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.
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).
Methylene blue will be given as minitablets in prepackaged sachets according to weight groups.

What is the study measuring?

Primary Outcome Measures

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

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.

Investigators

  • 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.

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

July 1, 2016

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

July 6, 2016

First Submitted That Met QC Criteria

July 8, 2016

First Posted (Estimate)

July 13, 2016

Study Record Updates

Last Update Posted (Estimate)

January 11, 2017

Last Update Submitted That Met QC Criteria

January 9, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

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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