Publication:
Antimalarial activity of KAF156 in falciparum and vivax malaria

Issued Date

2016-09-22

Resource Type

Article

ISSN

15334406
00284793

DOI

10.1056/NEJMoa1602250

Other identifier(s)

2-s2.0-84988838007

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

New England Journal of Medicine. Vol.375, No.12 (2016), 1152-1160

Suggested Citation

Nicholas J. White, Tran T. Duong, Chirapong Uthaisin, Fran'ois Nosten, Aung P. Phyo, Borimas Hanboonkunupakarn, Sasithon Pukrittayakamee, Podjanee Jittamala, Kittiphum Chuthasmit, Ming S. Cheung, Yiyan Feng, Ruobing Li, Baldur Magnusson, Marc Sultan, Daniela Wieser, Xiaolei Xun, Rong Zhao, Thierry T. Diagana, Peter Pertel, F. Joel Leong Antimalarial activity of KAF156 in falciparum and vivax malaria. New England Journal of Medicine. Vol.375, No.12 (2016), 1152-1160. doi:10.1056/NEJMoa1602250 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41132

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Title

Antimalarial activity of KAF156 in falciparum and vivax malaria

Author(s)

Nicholas J. White
 Tran T. Duong
 Chirapong Uthaisin
 Fran'ois Nosten
 Aung P. Phyo
 Borimas Hanboonkunupakarn
 Sasithon Pukrittayakamee
 Podjanee Jittamala
 Kittiphum Chuthasmit
 Ming S. Cheung
 Yiyan Feng
 Ruobing Li
 Baldur Magnusson
 Marc Sultan
 Daniela Wieser
 Xiaolei Xun
 Rong Zhao
 Thierry T. Diagana
 Peter Pertel
 F. Joel Leong

Other Contributor(s)

Mahidol-Oxford Tropical Medicine Research Unit
 Department of Clinical Tropical Medicine
 Mahidol University
 Phusing Hospital
 Mae Ramat District Hospital
 Nuffield Department of Clinical Medicine
 National Institute of Malaria, Parasitology and Entomology
 Novartis International AG
 Novartis Institutes for BioMedical Research
 Novartis Institutes for Biomedical Research
 Novartis Institute for Tropical Diseases Pte. Ltd.
 Novartis Institutes for BioMedical Research, Inc.

Abstract

© 2016 Massachusetts Medical Society. All rights reserved. Background KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. METHODS We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). RESULTS Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean ('SD) KAF156 terminal elimination half-life was 44.1'8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. CONCLUSIONS KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/41132

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Scopus 2016-2017