Malik Fady I, Robertson Laura A, Armas Danielle R, Robbie Edward P, Osmukhina Anna, Xu Donghong, Li Hanbin, Solomon Scott D
Research and Development, Cytokinetics, Inc, South San Francisco, California, USA.
Celerion, Inc, Tempe, Arizona, USA.
JACC Basic Transl Sci. 2022 Aug 10;7(8):763-775. doi: 10.1016/j.jacbts.2022.04.008. eCollection 2022 Aug.
This phase 1, randomized, double-blind, placebo-controlled study of aficamten (formerly CK-3773274) in healthy adults identified a pharmacologically active range of doses and exposures. At doses that were pharmacologically active (single doses of ≤50 mg or daily dosing of ≤10 mg for 14 or 17 days), aficamten appeared to be safe and well tolerated. Adverse events were generally mild and no more frequent than with placebo. Pharmacokinetic assessments showed dose proportionality over the range of single doses administered, and pharmacokinetics were not affected by administration with food or in otherwise healthy individuals with a cytochrome P450 2D6 poor metabolizer phenotype. (A Single and Multiple Ascending Dose Study of CK-3773274 in Health Adult Subjects; NCT03767855).
这项针对健康成年人的阿非卡坦（原名CK-3773274）1期随机、双盲、安慰剂对照研究确定了具有药理活性的剂量范围和暴露量。在具有药理活性的剂量下（单次剂量≤50毫克或每日剂量≤10毫克，持续14或17天），阿非卡坦似乎安全且耐受性良好。不良事件一般较轻，且不比安慰剂更频繁。药代动力学评估显示，在所给予的单次剂量范围内，剂量呈比例关系，且药代动力学不受与食物同服或在细胞色素P450 2D6代谢不良表型的其他健康个体中的影响。（CK-3773274在健康成年受试者中的单次和多次递增剂量研究；NCT03767855）
