Phase 2 Efficacy Study of Primaquine and Methylene Blue

University of California, San Francisco80 enrolled

Overview

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.

Protocol will be shared on request.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Malaria

Interventions

Sulphadoxine-pyrimethamineDRUG

Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine. Doses will be administered by weight.

0.25 mg/kg primaquineDRUG

Primaquine will be administered in an aqueous solution according to weight-based dosing.

Dihydroartemisinin-piperaquineDRUG

160mg/20mg or 320mg/40mg of dihydroartemisinin/piperaquine tablets will be used to administer weight-based doses.

Eligibility

Sex: MALEMin age: 5 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Malaria Research and Training Centre

Bamako, Mali

Outcomes

Primary Outcomes

Mosquito infectivity assessed through membrane feeding assays

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.

Time frame: 7 day

Secondary Outcomes

Gametocyte prevalence, density, and sex ratio measured microscopically and by molecular methods.

Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose.

Time frame: 42 days

Asexual parasite prevalence and density

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.

Time frame: 42 days

Safety measurements including hemoglobin and signs of hemolysis

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.

Time frame: 42 days

Peak plasma concentration (Cmax) of primaquine

Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

Time frame: 24 hours

Area under the concentration curve (AUC) of primaquine.

Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.

Time frame: 24 hours

Data from ClinicalTrials.gov

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