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The novel imidazolopiperazine KAF156 clears parasitemia rapidly in falciparum and vivax malaria

White, Nicholas and Thanh, Duong Tran and Uthaisin, Chirapong and Nosten, Francois and Phyo, Aung Pyae and Pukrittayakamee, Sasithon and Jittamala, Podjanee and Chuthasmit, Kittiphum and Cheung, Nicole and Feng, Elie and Li, Ruobing and Magnusson, Baldur and Sultan, Marc and Wieser, Daniela and Xun, Xiaolei and Zhao, Rong and Diagana, Thierry Tidiane and Pertel, Peter and Leong, Franz Joel Wen (2016) The novel imidazolopiperazine KAF156 clears parasitemia rapidly in falciparum and vivax malaria. New England journal of medicine : NEJM., 375 (12). pp. 1152-1160. ISSN 0028-4793

Abstract

BACKGROUND
KAF156 belongs to a new class of antimalarials (imidazolopiperazines), with broad-spectrum activity against asexual and sexual blood stages and the pre-erythrocytic liver stages of malaria parasites.
METHODS
We conducted a phase 2, open-label, two-part study in five centers in Thailand and Vietnam, to assess the antimalarial efficacy, safety, and adverse-event profile of KAF156 in adult patients with acute P. vivax or P.falciparum malaria. A multiple dose (400 mg once daily for 3 days) study assessing parasite clearance rates was followed by a single dose study in falciparum malaria (800 mg) assessing 28 day cure rates.
RESULTS
KAF156 was generally well tolerated, although there were significantly more adverse events reported in the single-dose cohort. Median (interquartile range) parasite clearance times were 45 (42 to 48) hours in falciparum malaria (N=10), and 24 (20 to 30) hours in vivax malaria (N=10) after the multiple dose regimen, and 49 (42 to 54) hours in falciparum malaria (N=21) after the single dose. The mean (SD) KAF 156 terminal elimination half-life was 44 (8.9) hours. One patient could not be treated because of repeated vomiting, and 8 of the 21 single dose recipients (38%) had recurrent P. falciparum infections by Day 29 (7 recrudescences and 1 reinfection).
CONCLUSIONS
KAF156 was relatively well tolerated and effective in treating adult patients with uncomplicated P. vivax or P. falciparum malaria.

Item Type: Article
Date Deposited: 12 Oct 2016 00:45
Last Modified: 12 Oct 2016 00:45
URI: https://oak.novartis.com/id/eprint/28035

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