Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina.

Abstract

OBJECTIVES:

The goal of this study was to assess the safety and tolerability of omecamtiv mecarbil treatment during symptom-limited exercise in patients with ischemic cardiomyopathy and angina. These patients may have increased vulnerability to prolongation of the systolic ejection time.

BACKGROUND:

Omecamtiv mecarbil is a selective cardiac myosin activator that augments cardiac contractility in patients with systolic heart failure through a dose-dependent increase in systolic ejection time.

METHODS:

In this double-blind, placebo-controlled study, patients with chronic heart failure were randomized 2:1 to receive omecamtiv mecarbil or placebo in 2 sequential cohorts of escalating doses designed to achieve plasma concentrations previously shown to increase systolic function. Patients underwent 2 symptom-limited exercise treadmill tests (ETTs) at baseline (ETT1 and ETT2) and again before the end of a 20-h infusion of omecamtiv mecarbil (ETT3).

RESULTS:

The primary pre-defined safety endpoint (i.e., the proportion of patients who stopped ETT3 because of angina at a stage earlier than baseline) was observed in 1 patient receiving placebo and none receiving omecamtiv mecarbil. No dose-dependent differences emerged in the proportion of patients stopping ETT3 for any reason or in the pattern of adverse events.

CONCLUSIONS:

Doses of omecamtiv mecarbil producing plasma concentrations previously shown to increase systolic function were well tolerated during exercise in these study patients with ischemic cardiomyopathy and angina. There was no indication that treatment increased the likelihood of myocardial ischemia in this high-risk population. (Pharmacokinetics [PK] and Tolerability of Intravenous [IV] and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina; NCT00682565).

• Authors: Barry H Greenberg, Willis Chou, Khalil G Saikali, Rafael Escandón, Jacqueline H Lee, Michael M Chen, Tatyana Treshkur, Irakli Megreladze, Scott M Wasserman, Paul Eisenberg, Fady I Malik, Andrew A Wolff, Tamaz Shaburishvili
• Journal: JACC. Heart failure (JACC Heart Fail) Vol. 3 Issue 1 Pg. 22-29 (Jan 2015) ISSN: 2213-1787 [Electronic] United States
• PMID: 25453536 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• omecamtiv mecarbil
• Urea

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Angina Pectoris (diagnosis, drug therapy, physiopathology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Tolerance
• Exercise (physiology)
• Exercise Test
• Female
• Follow-Up Studies
• Georgia (Republic)
• Humans
• Male
• Middle Aged
• Myocardial Contraction (drug effects)
• Myocardial Ischemia (diagnosis, drug therapy, physiopathology)
• Retrospective Studies
• Russia
• Treatment Outcome
• Urea (administration & dosage, analogs & derivatives)