Omecamtiv mecarbil is a novel, small-molecule, direct activator of cardiac myosin, the motor protein that causes cardiac contraction. It is being evaluated as a potential treatment of heart failure in both intravenous and oral formulations with application across the continuum of care for heart failure patients from in-hospital to outpatient settings.
DEVELOPMENT STATUS OF OMECAMTIV MECARBIL
Phase II Clinical Trials Details
Stable Heart Failure (iv) CY 1111
Phase I Clinical Trials Details
Multiple Formulations (oral) 20090727
Cytokinetics announced that a Phase I clinical trial conducted by Amgen in collaboration with Cytokinetics was completed in June 2012. This trial was designed to assess the safety, tolerability and pharmacokinetics of modified release oral formulations of omecamtiv mecarbil in healthy volunteers. The primary objective of this clinical trial was to determine the bioavailability of multiple modified release oral formulations of omecamtiv mecarbil following single dose administration under fasting conditions and to evaluate the effect of food on bioavailability. Cytokinetics and Amgen reviewed the data and based on the review of these data, the companies selected oral formulations of omecamtiv mecarbil from this Phase I trial that warrant further evaluation in patients with heart failure.
In June 2008, Cytokinetics announced results from a Phase I, single-center, two-part, open-label clinical trial, designed to evaluate modified release forms of omecamtiv mecarbil in healthy subjects. The primary objective of this trial was to assess the pharmacokinetics and relative bioavailability of three different oral modified release prototypes of omecamtiv mecarbil. The secondary objective of the trial was to determine whether there is an effect of food on the pharmacokinetics of one of these oral modified release prototypes of omecamtiv mecarbil. The single dose pharmacokinetics of one formulation in both the fasted and fed states demonstrated that it reduced Cmax as compared to the immediate release formulation without a substantial effect on overall bioavailability.
In June 2008, Cytokinetics announced the completion of a Phase I clinical trial of omecamtiv mecarbil designed to evaluate the pharmacokinetics of an oral formulation of omecamtiv mecarbil in healthy volunteers. The primary objective of this study was to evaluate the safety and tolerability of omecamtiv mecarbil after a single oral dose and after multiple oral doses to steady-state in healthy men and women. The secondary objective of this study was to evaluate the pharmacokinetics of omecamtiv mecarbil after a single oral dose and after multiple oral doses to steady-state and to compare the pharmacokinetic parameters between healthy men and women. This trial progressed from a single-blind, single-dose phase to a randomized, double-blind, placebo-controlled, multi-dose phase. Omecamtiv mecarbil was well-tolerated in the trial, with no drug-related serious adverse events.
Cytokinetics conducted a Phase I clinical trial designed to evaluate the potential for certain drug-drug interactions with omecamtiv mecarbil. The primary objective of this trial was to evaluate the effect of ketoconazole (a potent inhibitor of the drug-metabolizing enzyme, cytochrome P450 (CYP3A4)) at steady-state on the pharmacokinetics of a single oral dose of omecamtiv mecarbil in patients who are either extensive metabolizers (EM) or poor metabolizers (PM) with respect to their defined genotype for the drug-metabolizing enzyme CYP2D6. There were no clinically important differences observed between EM and PM subjects; furthermore, no clinically meaningful drug-drug interactions with either ketoconazole or diltiazem were identified in either EM or PM subjects.
Cytokinetics announced the results of a Phase I oral bioavailability study during a poster session at the 2007 Heart Failure Society of America (HFSA) Annual Meeting. The primary objective of this trial was to determine the bioavailability of an oral liquid and capsule formulation of omecamtiv mecarbil versus a reference intravenous infusion and, to determine the bioavailbility of the capsule dose in fed and fated states relative to the liquid dose. The authors concluded that the absolute bioavailability of omecamtiv mecarbil approached 100% for all formulations administered in the trial; food did not have a substantial effect on bioavailability and that the drug candidate was well tolerated in both intravenous and oral formulations.
Cytokinetics announced that data from the first-in-human Phase I clinical trial of omecamtiv mecarbil administered intravenously were presented at the Heart Failure Society of America (HFSA) Annual Meeting in September 2006 and the American Heart Association Scientific Sessions in November 2006. The primary objective of this trial was to evaluate the safety, tolerability and to identify the maximum tolerated dose (MTD). This clinical trial demonstrated that the MTD was 0.5 mg/kg/hr for the six-hour infusion in healthy volunteers. At this dose, the six-hour infusion of omecamtiv mecarbil produced a statistically significant increase in left ventricular ejection fraction as compared to placebo and a statistically significant increase in fractional shortening versus placebo. In this trial, omecamtiv mecarbil was well-tolerated when compared to placebo.