A Phase 1 Dose-Escalation Study of the Cardiac Myosin Inhibitor Aficamten in Healthy Participants

Abstract

This phase 1, randomized, double-blind, placebo-controlled study of aficamten (formerly CK-3773274) in healthy adults identified a pharmacologically active range of doses and exposures. At doses that were pharmacologically active (single doses of ≤50 mg or daily dosing of ≤10 mg for 14 or 17 days), aficamten appeared to be safe and well tolerated. Adverse events were generally mild and no more frequent than with placebo. Pharmacokinetic assessments showed dose proportionality over the range of single doses administered, and pharmacokinetics were not affected by administration with food or in otherwise healthy individuals with a cytochrome P450 2D6 poor metabolizer phenotype. (A Single and Multiple Ascending Dose Study of CK-3773274 in Health Adult Subjects; NCT03767855).

Keywords: AE, adverse event; AUC24, area under the plasma concentration–time curve from time 0 to 24 hours; CV%,, percent coefficient of variation; CYP, cytochrome P450; CYP2D6-PM, cytochrome P450 2D6 poor metabolizer phenotype; Cmax, maximum plasma drug concentration; DLRC, Dose Level Review Committee; ECG, electrocardiogram; HCM, hypertrophic cardiomyopathy; LV contractility; LV, left ventricle; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; MAD, multiple ascending dose; PD, pharmacodynamic; PK, pharmacokinetic; QTcF, QT interval corrected for heart rate using Fridericia’s formula; SAD, single ascending dose; TEAE, treatment-emergent adverse event; aficamten; cardiac myosin inhibitor; hypertrophic cardiomyopathy; phase 1.