Clinical trial NCT01743820: Phase2a Primaquine Dose Escalation Study
Official title: Phase 2a Dose Escalation Study of the Efficacy, Safety, and Pharmacokinetics of Low Dose Primaquine for Gametocytocidal Activity Against P. Falciparum in Sub-Saharan Africa and South East Asia
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: Shoklo Malaria Research Unit
name: Mahidol Oxford Tropical Medicine Research Unit
name: Bill and Melinda Gates Foundation
name: Wellcome Trust
First posted: 2012-12-06
Enrollment: 81
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of low single-dose primaquine for gametocidal activity against P.falciparum among adult glucose-6-phosphate dehydrogenase (G6PD)-normal malaria patients.


Eligibility criteria: Inclusion Criteria:

* Male
* Age \>= 18 years and \< 50 years
* Malaria blood thick film positive
* Presence of gametocytes on thick blood film
* Agrees to admission to study ward for 26 hours post diagnosis and available for follow up visits
* No allergies to study drugs
* Hemoglobin \>= 8 g/dl
* No evidence of severe or chronic disease
* Written, informed consent

Primary outcomes:
measure: mosquito infectivity assessed through membrane feeding
timeFrame: 7 days
Secondary outcomes:
measure: gametocyte prevalence and density
timeFrame: 28 days
measure: primaquine pharmacokinetics - area under the curve (AUC) of parent drug and metabolite
timeFrame: 24 hours
measure: asexual parasite prevalence and density
timeFrame: 28 days
measure: safety measurements including hemoglobin and signs of hemolysis
timeFrame: 28 days
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: Shoklo Malaria Research Unit
name: François Nosten, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gosling RD, Okell L, Mosha J, Chandramohan D. The role of antimalarial treatment in the elimination of malaria. Clin Microbiol Infect. 2011 Nov;17(11):1617-23. doi: 10.1111/j.1469-0691.2011.03660.x. Epub 2011 Sep 26.
citation: Baird JK, Schwartz E, Hoffman SL. Prevention and treatment of vivax malaria. Curr Infect Dis Rep. 2007 Jan;9(1):39-46. doi: 10.1007/s11908-007-0021-4.
citation: WHO (2011) World Malaria Report 2011. Geneva: World Health Organization.
citation: WHO (2010) Guidelines for the treatment of malaria, Second edition. Geneva: World Health Organization
citation: El-Sayed B, El-Zaki SE, Babiker H, Gadalla N, Ageep T, Mansour F, Baraka O, Milligan P, Babiker A. A randomized open-label trial of artesunate- sulfadoxine-pyrimethamine with or without primaquine for elimination of sub-microscopic P. falciparum parasitaemia and gametocyte carriage in eastern Sudan. PLoS One. 2007 Dec 12;2(12):e1311. doi: 10.1371/journal.pone.0001311.
citation: Shekalaghe SA, ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, Koenderink JB, Luty AJ, Whitty CJ, Drakeley C, Sauerwein RW, Bousema T. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother. 2010 May;54(5):1762-8. doi: 10.1128/AAC.01135-09. Epub 2010 Mar 1.
citation: Dicko A, Brown JM, Diawara H, Baber I, Mahamar A, Soumare HM, Sanogo K, Koita F, Keita S, Traore SF, Chen I, Poirot E, Hwang J, McCulloch C, Lanke K, Pett H, Niemi M, Nosten F, Bousema T, Gosling R. Primaquine to reduce transmission of Plasmodium falciparum malaria in Mali: a single-blind, dose-ranging, adaptive randomised phase 2 trial. Lancet Infect Dis. 2016 Jun;16(6):674-684. doi: 10.1016/S1473-3099(15)00479-X. Epub 2016 Feb 20.