Blood Schizonticidal Activity and Safety of Tafenoquine When Administered as Chemoprophylaxis to Healthy, Nonimmune Participants Followed by Blood Stage Plasmodium falciparum Challenge: A Randomized, Double-blind, Placebo-controlled Phase 1b Study.

Autor:	McCarthy JS; QIMR Berghofer Medical Research Institute, Brisbane, Queensland., Smith B; 60P Australia Pty Ltd, Sydney, New South Wales., Reid M; Graythan Regulatory Services Pty Ltd, Brisbane, Queensland, Australia.; Clinical Network Services Pty Ltd, Brisbane, Queensland, Australia., Berman J; Fast-Track Drugs and Biologicals LLC, North Potomac., Marquart L; QIMR Berghofer Medical Research Institute, Brisbane, Queensland., Dobbin C; Clinical Network Services Pty Ltd, Brisbane, Queensland, Australia., West L; Clinical Network Services Pty Ltd, Brisbane, Queensland, Australia., Read LT; US Army Medical Materiel Development Activity, Fort Detrick, Maryland., Dow GS; 60P Australia Pty Ltd, Sydney, New South Wales.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2019 Jul 18; Vol. 69 (3), pp. 480-486.
DOI:	10.1093/cid/ciy939
Abstrakt:	Background: Tafenoquine was recently approved for chemoprophylaxis of malaria. Its specific activity against liver and blood stages of Plasmodium species has been separately characterized in animals but not in humans. Methods: In this randomized, double-blind, placebo-controlled study, 16 malaria-naive, glucose-6-phosphate dehydrogenase-normal participants aged 20-42 years received tafenoquine chemoprophylaxis prior to challenge with blood stage Plasmodium falciparum. Participants were randomly assigned to either tafenoquine (n = 12) or placebo (n = 4) and took blinded study medication (single 200-mg dose) on days 1, 2, 3, and 10, followed by intravenous inoculation with approximately 2800 P. falciparum parasitized erythrocytes on day 13. The primary endpoint was the number of participants requiring rescue treatment with artemether/lumefantrine due to the onset of parasitemia as determined by quantitative polymerase chain reaction. Results: None of the 12 participants who received tafenoquine developed parasitemia, whereas all placebo participants developed parasitemia (P = .0005). Two cases of mild hemoglobin decrease and a single case of mild hyperbilirubinemia occurred in the tafenoquine group. Conclusions: Tafenoquine chemoprophylaxis is safe and effective in preventing malaria in healthy nonimmune participants challenged with blood stage P. falciparum. Clinical Trials Registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12617000102370. (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu