Dataset Information

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. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01524341.).

SUBMITTER: White NJ

PROVIDER: S-EPMC4143746 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Spiroindolone KAE609 for falciparum and vivax malaria.

White Nicholas J NJ Pukrittayakamee Sasithon S Phyo Aung Pyae AP Rueangweerayut Ronnatrai R Nosten François F Jittamala Podjanee P Jeeyapant Atthanee A Jain Jay Prakash JP Lefèvre Gilbert G Li Ruobing R Magnusson Baldur B Diagana Thierry T TT Leong F Joel FJ

The New England journal of medicine 20140701 5

<h4>Background</h4>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.<h4>Methods</h4>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 a ...[more]

PMID: 25075833

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Dataset Information

Spiroindolone KAE609 for falciparum and vivax malaria.

Publications

Spiroindolone KAE609 for falciparum and vivax malaria.

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