Spiroindolone KAE609 for Falciparum and Vivax Malaria
Spiroindolone KAE609 for Falciparum and Vivax Malaria
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DOI：
10.1056/nejmoa1315860
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发表时间：
2014-07-31
影响因子：
158.5
通讯作者：
Leong, F. Joel
中科院分区：
文献类型：
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作者：
White, Nicholas J.;Pukrittayakamee, Sasithon;Leong, F. Joel
背景KAE609（cipargamin；以前称为 NITD609，诺华热带病研究所）是一种新型合成抗疟螺吲哚酮类似物，对恶性疟原虫无性和有性阶段具有有效的剂量依赖性抗疟活性。方法我们在泰国的三个中心进行了一项 2 期开放标签研究，以评估其抗疟功效、安全性和不良事件概况。 KAE609，剂量为每天 30 毫克，持续 3 天，研究对象为患有无并发症的间日疟原虫疟疾（10 名患者）或恶性疟原虫疟疾（11 名患者）的两个连续队列。主要终点是寄生虫清除时间。 结果 每个队列中的中位寄生虫清除时间为 12 小时（四分位数范围，间日疟患者为 8 至 16 小时，恶性疟患者为 10 至 16 小时）。间日疟患者的寄生虫清除半衰期中位数为 0.95 小时（范围为 0.68 至 2.01；四分位数范围为 0.85 至 1.14），恶性疟患者为 0.90 小时（范围为 0.68 至 1.64；四分位数范围为 0.78 至 1.07）。相比之下，5076 名恶性疟患者中只有 19 名（
BACKGROUNDKAE609 (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.METHODSWe 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.RESULTSThe 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 (