CYTOKINETICS PRESENTS DATA FROM TRIAL OF MYOSIN ACTIVATOR

Cytokinetics has announced positive results from a first-in-humans, Phase I trial evaluating CK-1827452, a cardiac myosin activator, administered intravenously. Data from this double-blind, randomized, placebo-controlled, dose-escalation trial were presented at a meeting of the Heart Failure Society of America in Seattle. This trial was conducted to investigate the safety, tolerability, pharmacokinetics and pharmacodynamic profile of a six-hour infusion of CK-1827452 in healthy volunteers.

In the study, the maximum tolerated dose (MTD) was determined to be 0.5 mg/kg/hr for the six-hour infusion in healthy volunteers. At this dose, the six-hour infusion produced a mean increase in left ventricular ejection fraction of 6.8 absolute percentage points as compared with placebo. At the same dose, CK-1827452 also produced a mean increase in fractional shortening of 9.2 absolute percentage points versus placebo. These increases in indices of left ventricular function were associated with an 84-millisecond mean prolongation of systolic ejection time. These mean changes in ejection fraction, fractional shortening and ejection time were dose-proportional across the range of doses evaluated. In addition, CK-1827452 exhibited linear, dose-proportional pharmacokinetics.

At the MTD of 0.5 mg/kg/hr for 6 hours and below, CK-1827452 was well-tolerated when compared with placebo. In addition, CK-1827452 was clinically well-tolerated at 0.625 mg/kg/hr for six hours, but too few volunteers received this dose to define it as the MTD. At the end of the six-hour infusion at the MTD, mean standing systolic blood pressure fell 13.0 mmHg and mean supine systolic blood pressure fell 7.4 mmHg versus placebo. Up to and including the MTD, there was no dose-related increase in the overall incidence of adverse events.