Cytokinetics, Incorporated announced that in the first half of 2011, the company and its partner, Amgen Inc., plan to initiate a phase II b clinical trial of an intravenous formulation of omecamtiv mecarbil to evaluate its safety and efficacy in patients with left ventricular systolic dysfunction hospitalized for acute heart failure. This trial will be conducted by Amgen in collaboration with Cytokinetics. Amgen holds an exclusive, world-wide (excluding Japan) license to omecamtiv mecarbil and related compounds, subject to specified development and commercialization participation rights of Cytokinetics.
“This phase II b clinical trial was designed to evaluate specific heart failure symptoms to assess the potential clinical efficacy, safety, and tolerability of omecamtiv mecarbil for the treatment of patients hospitalized for acute heart failure,” stated Andrew A. Wolff, MD, FACC, Cytokinetics’ senior vice president of Clinical Research and Development and chief medical officer. “The objective of this clinical trial is to determine if the increases in left ventricular systolic function observed in patients with stable heart disease treated with omecamtiv mecarbil in an earlier phase II a trial may translate into a clinical benefit in patients hospitalized for acute heart failure, a large and growing population that is underserved by currently available treatments.”
“This phase II b clinical trial represents a significant step forward for this program,” stated Robert I. Blum, Cytokinetics’ president and chief executive officer. “The progress in the clinical development of omecamtiv mecarbil, combined with the recent successful completion of an Evidence of Effect phase II a clinical trial of our fast skeletal muscle troponin activator, CK-2017357, in patients with ALS, demonstrates the promise of our focused research and development activities in the biology of muscle function.”
Phase II b clinical trial is planned to be an international, multi-centre, randomized, double-blind, placebo-controlled study in approximately 600 patients, enrolled sequentially in 3 ascending-dose cohorts. In each cohort, patients will be randomized to receive omecamtiv mecarbil or placebo. The primary objective of the phase II b clinical trial will be to evaluate the effect of 48 hours of intravenous (IV) omecamtiv mecarbil compared to placebo on dyspnea (or shortness of breath) in patients with left ventricular systolic dysfunction hospitalized for acute heart failure.
The secondary objectives are to assess the safety and tolerability of 3 dose levels of IV omecamtiv mecarbil compared with placebo and to evaluate the effects of 48 hours of treatment with IV omecamtiv mecarbil on additional measures of dyspnea, patients’ global assessments, change in N-terminal pro brain-type natriuretic peptide (a biomarker associated with the severity of heart failure) and short-term clinical outcomes in these patients. In addition, the trial will evaluate the relationship between omecamtiv mecarbil plasma concentrations and echocardiographic parameters in patients with acute heart failure.
Cytokinetics and its partner Amgen are in active discussions regarding the oral development strategy for omecamtiv mecarbil. The company anticipates that these plans may include studies designed to investigate the safety, tolerability and pharmacokinetics of multiple oral formulations of omecamtiv mecarbil. Additional information will be provided following the finalization of these plans.
Omecamtiv mecarbil, a novel cardiac muscle myosin activator, has been the subject of a clinical trials programme comprised of multiple phase I and phase II a trials previously conducted under the sponsorship of Cytokinetics. This programme was designed to evaluate the safety, tolerability, pharmacodynamic and pharmacokinetic profiles of both intravenous and oral formulations of omecamtiv mecarbil for the potential treatment of heart failure across the continuum of care, in both hospital and outpatient settings.
Two phase II a clinical trials of omecamtiv mecarbil from this programme have been completed. In addition, five phase I clinical trials of omecamtiv mecarbil were conducted in healthy subjects: a first-time-in-humans study evaluating an intravenous formulation, an oral bioavailability study evaluating both intravenous and oral formulations, and three studies of oral formulations: a drug-drug interaction study, a dose proportionality study and a study evaluating modified-release formulations. Data from each of these trials have been reported previously.
Cytokinetics is a clinical-stage biopharmaceutical company focused on the discovery and development of novel small molecule therapeutics that modulate muscle function for the potential treatment of serious diseases and medical conditions. Its lead drug candidate from its cardiac muscle contractility programme, omecamtiv mecarbil (formerly CK-1827452), is in clinical development for the potential treatment of heart failure.