White, Nicholas J, Pukrittayakamee, Sasithon, Phyo, Aung P, Rueangweerayut, Ronnatrai, Nosten, François, Jittmala, Podjanee, Jeeyapant , Atthanee, Jain, Jay Prakash, Lefevre, Gilbert, Li, Ruobing, Magnusson, Baldur, Diagana, Thierry Tidiane and Leong, Franz Joel Wen (2013) The novel spiroindolone KAE609 clears parasitemia rapidly in falciparum and vivax malaria. The Novel Spiroindolone KAE609 Clears Parasitemia Rapidly.

Abstract

BACKGROUND
KAE609 (NITD609) is a novel synthetic antimalarial spiroindolone analogue with potent, dose-dependent antimalarial activity against asexual and sexual stages of Plasmodium falciparum. It is the first molecule with a known novel mechanism of action to enter phase II studies for the treatment of malaria for 23 years.
METHODS
We conducted a phase II, open-label study at three centers in Thailand to assess the antimalarial efficacy (primary objective: parasite clearance time [PCT]), safety, and tolerability of KAE609, 30 mg/day for 3 days, in two sequential cohorts of adult patients with uncomplicated P. vivax or P. falciparum malaria.
RESULTS
Parasitemia cleared very rapidly; the median PCT was 12 hours in both cohorts (interquartile range [IQR]: 8 to 16 hours in P. vivax and 10 to 16 hours in P. falciparum infections). Median parasite clearance half-lives were 0.90 hours (range: 0.68–1.64; IQR: 0.78–1.07) in falciparum (N = 11), and 0.95 hours (range: 0.68–2.01; IQR: 0.85–1.14) in vivax malaria (N = 10), whereas only 19 (0.37%) of 5076 falciparum patients treated with oal artesunate in South-East Asia had parasite clearance half-lives less than 1 hour. KAE609 was well tolerated in this study, there were no drug-attributable severe adverse events, and all patients recovered uneventfully. The KAE609 mean (range) terminal elimination half-life was 21 (11.3 to 37.6) hours supporting a once-daily oral dosing regimen.
CONCLUSIONS
KAE609, 30 mg daily for 3 days, was well tolerated and very rapidly effective in adult patients with uncomplicated P. vivax or P. falciparum malaria.
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Item Type:	Article
Keywords:	KAE609, NITD609, malaria, Plasmodium falciparum, Plasmodium vivax
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/21203