Abstract | INTRODUCTION: Current available inotropic agents increase cardiac contractility, but are associated with myocardial ischemia, arrhythmias, and mortality. A novel selective cardiac myosin activator, omecamtiv mecarbil ( CK-1827452/ AMG-423) is a small molecule that activates the sarcomere proteins directly, resulting in prolonged systolic ejection time and increased cardiac contractility. AREAS COVERED: EXPERT OPINION: Results of phase I and phase II studies demonstrate that omecamtiv mecarbil is safe and well tolerated both as an intravenous and oral formulation. In healthy volunteers and chronic systolic heart failure patients, administration of omecamtiv mecarbil resulted in a concentration-dependent increase of left ventricular ejection time, ejection fraction, fractional shortening, and stroke volume. The first results of a double-blind, randomized, placebo-controlled phase IIb dose-finding study with the oral formulation of omecamtiv mecarbil demonstrated beneficial effects on cardiac function and N-terminal pro- brain natriuretic peptide levels. This study will provide essential dosing information for the requisite phase III trials which will investigate whether the beneficial effects of omecamtiv mecarbil translate into improved clinical outcomes.
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Authors | Licette Cy Liu, Bernard Dorhout, Peter van der Meer, John R Teerlink, Adriaan A Voors |
Journal | Expert opinion on investigational drugs
(Expert Opin Investig Drugs)
Vol. 25
Issue 1
Pg. 117-27
( 2016)
ISSN: 1744-7658 [Electronic] England |
PMID | 26587768
(Publication Type: Journal Article, Review)
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Chemical References |
- Cardiotonic Agents
- omecamtiv mecarbil
- Urea
- Cardiac Myosins
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Topics |
- Animals
- Cardiac Myosins
(drug effects, metabolism)
- Cardiotonic Agents
(adverse effects, pharmacology, therapeutic use)
- Disease Models, Animal
- Heart Failure, Systolic
(drug therapy, physiopathology)
- Humans
- Myocardial Contraction
(drug effects)
- Randomized Controlled Trials as Topic
- Urea
(adverse effects, analogs & derivatives, pharmacology, therapeutic use)
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