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

Jinsy A. Andrews, Timothy M. Miller, Vipin Vijayakumar, Randall Stoltz, Joyce K. James, Lisa Meng, Andrew A. Wolff, Fady I. Malik

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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.

Original languageEnglish
Pages (from-to)729-734
Number of pages6
JournalMuscle and Nerve
Volume57
Issue number5
DOIs
StatePublished - May 2018

Keywords

  • CK-2127107
  • fast skeletal muscle troponin activator
  • force-frequency relationship
  • phase 1
  • skeletal muscle

Fingerprint

Dive into the research topics of 'CK-2127107 amplifies skeletal muscle response to nerve activation in humans'. Together they form a unique fingerprint.

Cite this