Department of Internal Medicine, University of Gondar Hospital, Gondar, Ethiopia.
Jimma University Clinical Trial Unit, Jimma University Institute of Health, Jimma, Ethiopia.
Am J Trop Med Hyg. 2022 Dec 5;108(1):81-84. doi: 10.4269/ajtmh.22-0567. Print 2023 Jan 11.
An open label, phase IIa study conducted in Ethiopia evaluated the efficacy, safety, tolerability, and pharmacokinetics of a single 120-mg dose of the phosphatidylinositol 4-kinase inhibitor MMV390048 in Plasmodium vivax malaria. The study was not completed for operational reasons and emerging teratotoxicity data. For the eight adult male patients enrolled, adequate clinical and parasitological response at day 14 (primary endpoint) was 100% (8/8). Asexual parasites and gametocytes were cleared in all patients by 66 and 78 hours postdose, respectively. There were two recurrent P. vivax infections (days 20 and 28) and a new Plasmodium falciparum infection (day 22). MMV390048 exposure in P. vivax patients was lower than previously observed for healthy volunteers. Mild adverse events, mainly headache and gastrointestinal symptoms, were reported by eight patients. Single-dose MMV390048 (120 mg) rapidly cleared asexual parasites and gametocytes in patients with P. vivax malaria and was well tolerated.
在埃塞俄比亚进行的一项开放标签、2 期 a 研究评估了单剂量 120 毫克磷脂酰肌醇 4-激酶抑制剂 MMV390048 治疗间日疟原虫疟疾的疗效、安全性、耐受性和药代动力学。由于操作原因和新出现的致畸毒性数据，该研究未完成。在入组的 8 名成年男性患者中，第 14 天（主要终点）有 100%（8/8）的充分临床和寄生虫学应答。所有患者的无性寄生虫和配子体分别在给药后 66 小时和 78 小时清除。有 2 例复发性间日疟原虫感染（第 20 天和第 28 天）和 1 例新的恶性疟原虫感染（第 22 天）。间日疟原虫患者的 MMV390048 暴露量低于先前观察到的健康志愿者。8 名患者报告了轻度不良事件，主要是头痛和胃肠道症状。单剂量 MMV390048（120mg）可快速清除间日疟原虫患者的无性寄生虫和配子体，且耐受性良好。
