Switchability and Minimal Effect of Food Effect on Pharmacokinetics of Modified Release Tablet Strengths of Omecamtiv Mecarbil, a Cardiac Myosin Activator.

Trivedi, Ashit; Oberoi, Rajneet K; Mackowski, Mia; Jafarinasabian, Pegah; Zhang, Hanze; Flach, Stephen; Simiens, Mary Ann; Terminello, Bianca; Abbasi, Siddique; Dutta, Sandeep; Lee, Edward

Omecamtiv mecarbil (OM) is a cardiac myosin activator in clinical development for the treatment of heart failure. The effect of food on the pharmacokinetics of 25, 37.5, and 50 mg strength modified release (MR) tablets and bioequivalence of two 25 mg versus one 50 mg MR tablet were evaluated in two open-label, randomized, cross-over studies in healthy subjects. Subjects received two 25 mg or one 50 mg OM MR tablets under fed or fasted states in Study 1 (n=39), and single oral doses of 25 and 37.5 mg OM MR tablets and to assess its relative bioavailability to the 25 mg MR tablet, a 25 mg oral solution under fed or fasted states in Study 2 (n=34). The area under the concentration-time curve (AUC) and maximum observed concentration (Cmax ) of 25, 37.5, or 50 mg OM MR tablets were approximately 13-22% higher and 31-40% higher, respectively, when taken with food. The two 25 mg and one 50 mg OM MR tablets were bioequivalent (90% confidence intervals (CIs)) of the geometric mean ratios (GMRs) for Cmax and AUC of OM were within 0.8 to 1.25) under fasted or fed state. OM was well tolerated and all treatment-emergent events were mild in severity and resolved by the end of the study. In conclusion, these studies demonstrated that the effect of food on OM pharmacokinetics was minimal at all three studied strengths of the MR tablets, and two 25 mg MR tablets may be switched for one 50 mg MR tablet. (EudraCT Number: 2019-003683-44) This article is protected by copyright. All rights reserved.