CYTOKINETICS BEGINS STUDY OF ORALLY ADMINISTERED CK-1827452

Cytokinetics has initiated a Phase I trial evaluating the pharmacokinetic profile of CK-1827452 when administered orally to healthy volunteers. CK-1827452 is a direct cardiac myosin activator under evaluation as a potential treatment for patients with acute and chronic heart failure. A recently completed Phase I trial in healthy volunteers evaluated an intravenous formulation of CK-1827452. Pharmacokinetic data from that clinical trial suggests that the half-life of CK-1827452 is sufficiently long to support development of oral dosing.

In the first Phase I trial, the maximum tolerated dose (MTD) was determined to be 0.5 mg/kg/hr in healthy volunteers. At this dose, the six-hour infusion of CK-1827452 produced statistically significant and clinically relevant increases in ejection fraction and fractional shortening, as measured from baseline to the end of the infusion, in comparison to placebo. These clinically relevant increases in cardiac function were associated with a statistically significant prolongation of systolic ejection time. At the MTD, CK-1827452 was well-tolerated compared with placebo. Across the dosing levels, infusions of CK-1827452 were characterized by linear, dose-proportional pharmacokinetics and produced dose-dependent pharmacodynamic effects.