Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California, 94080, USA.
Covance, Inc., Evansville, Indiana, USA.
Muscle Nerve. 2018 May;57(5):729-734. doi: 10.1002/mus.26017. Epub 2017 Dec 11.
Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-2127107 (CK-107), a next-generation fast skeletal muscle troponin activator (FSTA), in healthy participants. We tested the hypothesis that CK-107 would amplify the force-frequency response of muscle in humans.
To assess the force-frequency response, participants received single doses of CK-107 and placebo in a randomized, double-blind, 4-period, crossover study. The force-frequency response of foot dorsiflexion following stimulation of the deep fibular nerve to activate the tibialis anterior muscle was assessed.
CK-107 significantly increased tibialis anterior muscle response with increasing dose and plasma concentration in a frequency-dependent manner; the largest increase in peak force was ∼60% at 10 Hz.
CK-107 appears more potent and produced larger increases in force than tirasemtiv-a first-generation FSTA-in a similar pharmacodynamic study, thereby supporting its development for improvement of muscle function of patients. Muscle Nerve 57: 729-734, 2018.
三项研究评估了新一代快速骨骼肌肌钙蛋白激活剂（FSTA）CK-2127107（CK-107）在健康参与者中的安全性、耐受性、药代动力学和药效学。我们检验了如下假说，即 CK-107 将增强人类肌肉的力频率反应。
为了评估力频率反应，参与者在一项随机、双盲、4 期交叉研究中接受了 CK-107 和安慰剂的单次剂量。通过刺激腓深神经来激活胫骨前肌，评估足背屈的力频率反应。
CK-107 以频率依赖性的方式显著增加了胫骨前肌的反应，随着剂量和血浆浓度的增加而增加；在 10 Hz 时，最大峰值力增加约 60%。
在一项类似的药效学研究中，CK-107 比第一代 FSTA 替瑞斯美汀显示出更强的效力，并产生更大的力增加，从而支持其开发用于改善患者的肌肉功能。肌肉神经 57：729-734，2018 年。
