Cytokinetics Incorporated has announced the initiation of a phase II clinical trials programme evaluating CK-1827452, a novel cardiac myosin activator for the potential treatment of patients with either acutely decompensated or chronic heart failure.

The first patient has been dosed in the first phase IIa clinical trial, which is designed to evaluate the safety, tolerability, pharmacodynamic and pharmacokinetic profile of an intravenous formulation of CK-1827452 in patients with stable heart failure. CK-1827452 is the subject of a Collaboration and Option Agreement recently executed by Cytokinetics with Amgen Inc.

This first phase II clinical trial, now underway in the United Kingdom, is a multi-centre, double-blind, randomised, placebo-controlled, dose-escalation, pharmacokinetic and pharmacodynamic study of CK-1827452 in patients with stable heart failure. The primary objective of this trial is to evaluate the safety and tolerability of CK-1827452 administered as an intravenous infusion to stable heart failure patients.

The secondary objectives of this trial are to establish a relationship between plasma concentration and pharmacodynamic effect for CK-1827452 and to determine the pharmacokinetics of CK-1827452 in stable heart failure patients. In addition to routine assessments of vital signs, blood samples and ECG monitoring, echocardiograms will be performed to evaluate cardiac function at various pre-defined time points.

The clinical trial will consist of at least five cohorts of eight patients with stable heart failure. The first three of these cohorts will each undergo four treatment periods; patients will receive three escalating active doses of CK-1827452 administered intravenously and one placebo treatment, which will be randomised into the dose escalation sequence. Patients in the fourth and fifth cohorts are planned to receive only a single dose level of CK-1827452. In each cohort, patients will receive a one-hour loading infusion to rapidly achieve a target plasma concentration of CK-1827452, followed by a slower infusion intended to maintain that plasma concentration. These maintenance infusions are planned to be one hour in duration in the first two cohorts, and 23 hours in duration in the last three cohorts.

This first phase II clinical trial for CK-1827452 is part of a clinical trials program, to be conducted by Cytokinetics, which is planned to be comprised of phase I and phase II trials designed to evaluate the safety and efficacy of CK-1827452 in a diversity of patients, including those with stable heart failure, ischemic heart disease, impaired renal function and acutely decompensated heart failure, and patients with chronic heart failure at increased risk for death and hospital admission for heart failure. These trials are planned to evaluate the safety and efficacy of CK-1827452, in both intravenous and oral formulations, for the potential treatment of heart failure across the continuum of care, in both hospital and outpatient settings.

"We are pleased to initiate the phase II clinical trials programme for CK-1827452," stated Andrew A. Wolff, F.A.C.C., Cytokinetics' senior vice president of clinical research and development and chief medical officer. "The data from this first phase IIa clinical trial will help us to select dosing regimens for further study in later clinical trials of CK-1827452 in patient populations with heart failure of increasing severity."