Cytokinetics reports positive results from Phase IIa heart failure trial

Cytokinetics has announced positive results from a final Phase IIa clinical trial evaluating CK-1827452 in stable heart failure patients.

The clinical trial was multi-center, double-blind, randomized and placebo-controlled. The primary objective of this clinical trial was to evaluate the safety and tolerability of CK-1827452 administered as an intravenous infusion to stable heart failure patients. The secondary objectives were to establish a relationship between plasma concentration and pharmacodynamic effect for CK-1827452 and to determine the pharmacokinetics of CK-1827452 in this population. Overall, in 45 patients, a total of 151 treatment periods were initiated.

The study concluded that CK-1827452 increased systolic ejection time, stroke volume, cardiac output, fractional shortening, and ejection fraction in a concentration dependent manner (p<0.0001, p<0.0001, p<0.0005, p<0.0001, and p<0.009, respectively). More specifically, statistically significant increases were demonstrated in systolic ejection time (p<0.0001) and fractional shortening (p<0.04) at plasma concentrations greater than 100ng/ml, in stroke volume (p<0.01) at greater than 200ng/ml, and in cardiac output (p<0.02) at greater than 300ng/ml, the company said. At plasma concentrations greater than 400ng/ml, increases in stroke volume and cardiac output appeared to plateau in association with concentration dependent decline in heart rate (p<0.0001).

In addition, the data demonstrated statistically significant correlations between increasing CK-1827452 plasma concentration and decreases in left ventricular end-systolic volume (p<0.0001) and left ventricular end-diastolic volume (p<0.0005). The effects of CK-1827452 on systolic ejection time and stroke volume appeared to be persistent over a period of a 24-hour period, the company added. With 72 hours of infusion, decreases in ventricular volumes appeared sustained.

The study concluded that the improvements in cardiac systolic performance accompanied by the declines in left ventricular volumes observed in this trial may have been the consequence of decreases in filling pressure.

CK-1827452 appeared to be well-tolerated in stable heart failure patients over a range of plasma concentrations during continuous intravenous administration during this clinical trial.