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Clinical Trial
. 2018 May;57(5):729-734.
doi: 10.1002/mus.26017. Epub 2017 Dec 11.

CK-2127107 amplifies skeletal muscle response to nerve activation in humans

Jinsy A Andrews  1 , Timothy M Miller  1 , Vipin Vijayakumar  1 , Randall Stoltz  2 , Joyce K James  1 , Lisa Meng  1 , Andrew A Wolff  1 , Fady I Malik  1
Affiliations
Clinical Trial

CK-2127107 amplifies skeletal muscle response to nerve activation in humans

Jinsy A Andrews et al. Muscle Nerve. 2018 May.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: CK-2127107; fast skeletal muscle troponin activator; force-frequency relationship; phase 1; skeletal muscle.

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Figures

Figure 1
Figure 1
Placebo‐corrected summed percentage change from baseline (SEM) of peak force (ΣF) with CK‐107 treatment by time. *P < 0.05, † P < 0.01, ‡ P < 0.001 for least‐squares mean difference from placebo. CK‐107, CK‐2127107.
Figure 2
Figure 2
Placebo‐corrected percent changes in peak force (%F) at each frequency by CK‐107 concentration range. *P < 0.05, † P < 0.001, ‡ P < 0.0001 for least‐squares mean difference from placebo. CK‐107, CK‐2127107.
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