PMID- 37680714
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230910
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and 
      multiple doses of aficamten in healthy Chinese participants: a randomized, 
      double-blind, placebo-controlled, phase 1 study.
PG  - 1227470
LID - 10.3389/fphar.2023.1227470 [doi]
LID - 1227470
AB  - Objectives: Aficamten is a selective, small-molecule allosteric inhibitor of 
      cardiac sarcomere being developed as a chronic oral treatment for patients with 
      symptomatic obstructive hypertrophic cardiomyopathy. This was the 
      first-in-Chinese study aiming to investigate the safety, tolerability, 
      pharmacokinetics, and pharmacodynamics of aficamten in healthy adults. Methods: 
      This double-blind, randomized, placebo-controlled, phase 1 study was conducted in 
      28 healthy male and female Chinese participants after single ascending dose (SAD) 
      and multi-dose (MD) administrations of aficamten. In the SAD cohort, 16 
      participants were randomized to receive a single oral dose of aficamten: 10 mg, 
      20 mg, or placebo. In the MD cohort, 12 participants were randomized to receive 
      multiple doses of aficamten: 5 mg or placebo once daily for 14 days. Safety was 
      monitored throughout the study with electrocardiograms, echocardiograms, clinical 
      laboratory tests, and reporting of adverse events (AEs). Pharmacokinetic profiles 
      of aficamten and metabolites, as well as CYP2D6 genetic impact, were evaluated. 
      Results: A total of 35 treatment-emergent AEs were reported by 14 (50%) 
      participants with mild severity. There were no serious AEs or adverse decreases 
      in left ventricular ejection fraction below 50% during the study. Aficamten was 
      dose-proportional over the dose range of 5-20 mg and accumulated in the MD 
      cohort. Conclusion: Aficamten was safe and well-tolerated in the healthy Chinese 
      adult participants. The pharmacokinetics of aficamten in the Chinese population 
      was comparable to those previously found in Western participants. These phase 1 
      data support the progression of aficamten into future clinical studies in Chinese 
      patients. Clinical Trial registration: https://clinicaltrials.gov, identifier: 
      NCT04783766.
CI  - Copyright (c) 2023 Zhao, Liu, Tian, Fang, Yu, Wu, Liu, Wan, Li, Luo, Li, Liu, He, 
      Chen, Li, Xu, Wang and Han.
FAU - Zhao, Xue
AU  - Zhao X
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Liu, Hongzhong
AU  - Liu H
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Tian, Wei
AU  - Tian W
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Fang, Ligang
AU  - Fang L
AD  - Internal Medicine-Cardiovascular Department, Peking Union Medical College 
      Hospital, Beijing, China.
FAU - Yu, Mengyang
AU  - Yu M
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Wu, Xiaofei
AU  - Wu X
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Liu, Aijing
AU  - Liu A
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Wan, Ruijie
AU  - Wan R
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Li, Li
AU  - Li L
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Luo, Jinghui
AU  - Luo J
AD  - Ji Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, China.
FAU - Li, Yuqiong
AU  - Li Y
AD  - Ji Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, China.
FAU - Liu, Bo
AU  - Liu B
AD  - Ji Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, China.
FAU - He, Yu
AU  - He Y
AD  - Ji Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, China.
FAU - Chen, Xiaowen
AU  - Chen X
AD  - Ji Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, China.
FAU - Li, Yuan
AU  - Li Y
AD  - Ji Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, China.
FAU - Xu, Donghong
AU  - Xu D
AD  - Cytokinetics, Incorporated, South San Francisco, CA, United States.
FAU - Wang, Hongyun
AU  - Wang H
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
FAU - Han, Xiaohong
AU  - Han X
AD  - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 
      Beijing, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT04783766
PT  - Journal Article
DEP - 20230823
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10482267
OTO - NOTNLM
OT  - Chinese participants
OT  - aficamten
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - safety
COIS- Authors JL, YL, BL, YH, XC, and YL were employed by the company Ji Xing 
      Pharmaceuticals (Shanghai) Co., Ltd., and author DX was employed by the company 
      Cytokinetics, Inc. The remaining authors declare that the research was conducted 
      in the absence of any commercial or financial relationships that could be 
      construed as a potential conflict of interest.
EDAT- 2023/09/08 06:42
MHDA- 2023/09/08 06:43
PMCR- 2023/08/23
CRDT- 2023/09/08 04:05
PHST- 2023/05/25 00:00 [received]
PHST- 2023/08/10 00:00 [accepted]
PHST- 2023/09/08 06:43 [medline]
PHST- 2023/09/08 06:42 [pubmed]
PHST- 2023/09/08 04:05 [entrez]
PHST- 2023/08/23 00:00 [pmc-release]
AID - 1227470 [pii]
AID - 10.3389/fphar.2023.1227470 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Aug 23;14:1227470. doi: 10.3389/fphar.2023.1227470. 
      eCollection 2023.