Publication: Spiroindolone KAE609 for falciparum and vivax malaria
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Issued Date
2014-01-01
Resource Type
ISSN
15334406
00284793
00284793
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2-s2.0-84904909454
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Mahidol University
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SCOPUS
Bibliographic Citation
New England Journal of Medicine. Vol.371, No.5 (2014), 403-410
Suggested Citation
Nicholas J. White, Sasithon Pukrittayakamee, Aung Pyae Phyo, Ronnatrai Rueangweerayut, François Nosten, Podjanee Jittamala, Atthanee Jeeyapant, Jay Prakash Jain, Gilbert Lefèvre, Ruobing Li, Baldur Magnusson, Thierry T. Diagana, F. Joel Leong Spiroindolone KAE609 for falciparum and vivax malaria. New England Journal of Medicine. Vol.371, No.5 (2014), 403-410. doi:10.1056/NEJMoa1315860 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/34832
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Title
Spiroindolone KAE609 for falciparum and vivax malaria
Abstract
BACKGROUND: KAE609 (cipargamin; formerly NITD609, Novartis Institute for Tropical Diseases) is a new synthetic antimalarial spiroindolone analogue with potent, dose-dependent antimalarial activity against asexual and sexual stages of Plasmodium falciparum. METHODS: We conducted a phase 2, open-label study at three centers in Thailand to assess the antimalarial efficacy, safety, and adverse-event profile of KAE609, at a dose of 30 mg per day for 3 days, in two sequential cohorts of adults with uncomplicated P. vivax malaria (10 patients) or P. falciparum malaria (11). The primary end point was the parasite clearance time. RESULTS: The median parasite clearance time was 12 hours in each cohort (interquartile range, 8 to 16 hours in patients with P. vivax malaria and 10 to 16 hours in those with P. falciparum malaria). The median half-lives for parasite clearance were 0.95 hours (range, 0.68 to 2.01; interquartile range, 0.85 to 1.14) in the patients with P. vivax malaria and 0.90 hours (range, 0.68 to 1.64; interquartile range, 0.78 to 1.07) in those with P. falciparum malaria. By comparison, only 19 of 5076 patients with P. falciparum malaria (<1%) who were treated with oral artesunate in Southeast Asia had a parasite clearance half-life of less than 1 hour. Adverse events were reported in 14 patients (67%), with nausea being the most common. The adverse events were generally mild and did not lead to any discontinuations of the drug. The mean terminal half-life for the elimination of KAE609 was 20.8 hours (range, 11.3 to 37.6), supporting a once-daily oral dosing regimen. CONCLUSIONS: KAE609, at dose of 30 mg daily for 3 days, cleared parasitemia rapidly in adults with uncomplicated P. vivax or P. falciparum malaria. Copyright © 2014 Massachusetts Medical Society.