Clinical trial NCT02831023: Phase 2 Efficacy Study of Primaquine and Methylene Blue
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Malaria Research and Training Center, Bamako, Mali
name: Radboud University Medical Center
name: London School of Hygiene and Tropical Medicine
name: Heidelberg University
name: Bill and Melinda Gates Foundation
First posted: 2016-07-13
Enrollment: 80
Sex: MALE
Minimum age (years): 5
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Protocol will be shared on request.

Eligibility criteria: 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

Primary outcomes:
measure: Mosquito infectivity assessed through membrane feeding assays
timeFrame: 7 day
Secondary outcomes:
measure: Gametocyte prevalence, density, and sex ratio measured microscopically and by molecular methods.
timeFrame: 42 days
measure: Asexual parasite prevalence and density
timeFrame: 42 days
measure: Safety measurements including hemoglobin and signs of hemolysis
timeFrame: 42 days
measure: Peak plasma concentration (Cmax) of primaquine
timeFrame: 24 hours
measure: Area under the concentration curve (AUC) of primaquine.
timeFrame: 24 hours
measure: Elimination half life (t1/2) of primaquine
timeFrame: 24 hours
measure: Peak plasma concentration (Cmax) of methylene blue
timeFrame: 24 hours
measure: Area under the concentration curve (AUC) of methylene blue
timeFrame: 24 hours
measure: Elimination half life (t1/2) of methylene blue
timeFrame: 24 hours
measure: Peak plasma concentration (Cmax) of sulphadoxine-pyrimethamine
timeFrame: 24 hours
measure: Area under the concentration curve (AUC) of sulphadoxine-pyrimethamine
timeFrame: 24 hours
measure: Elimination half-life (t1/2) of sulphadoxine-pyrimethamine
timeFrame: 24 hours
measure: Peak plasma concentration (Cmax) of dihydroartemisinin-piperaquine
timeFrame: 24 hours
measure: Area under the concentration curve (AUC) of dihydroartemisinin-piperaquine
timeFrame: 24 hours
measure: Elimination half-life (t1/2) of dihydroartemisinin-piperaquine
timeFrame: 24 hours
measure: Identification of cytochrome P450 (CYP) 2D6 and G6PD polymorphisms
timeFrame: 1 hour
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: Malaria Research and Training Centre
Study officials:
affiliation: University of California, San Francisco
name: Roland Gosling, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Malaria Research and Training Centre
name: Alassane Dicko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Teun Bousema, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dicko A, Roh ME, Diawara H, Mahamar A, Soumare HM, Lanke K, Bradley J, Sanogo K, Kone DT, Diarra K, Keita S, Issiaka D, Traore SF, McCulloch C, Stone WJR, Hwang J, Muller O, Brown JM, Srinivasan V, Drakeley C, Gosling R, Chen I, Bousema T. Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial. Lancet Infect Dis. 2018 Jun;18(6):627-639. doi: 10.1016/S1473-3099(18)30044-6. Epub 2018 Feb 6.