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

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

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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electrocardiography
  • Electromyography
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Muscle Fibers, Fast-Twitch / drug effects*
  • Muscle, Skeletal / drug effects*
  • Neurologic Examination
  • Troponin / metabolism*
  • Young Adult

Substances

  • Troponin