Based on the Safety Review Committee’s review of safety data from the first cohort of patients, the committee has recommended that the company open the second cohort of this clinical trial for enrollment.
This double-blind, randomized, placebo-controlled Phase IIa clinical trial is designed to evaluate both intravenous and oral formulations of CK-1827452 in patients with ischemic cardiomyopathy and angina. The primary objective of this trial is to assess the effect of intravenous CK-1827452 on symptom-limited treadmill exercise tolerance. The secondary objective of this trial is to assess the tolerability and resulting plasma concentrations of CK-1827452 administered as an oral formulation.
The trial is designed to evaluate two cohorts of 45 patients each with ischemic cardiomyopathy and angina and an ejection fraction of less than or equal to 35%. Patients undergo two symptom-limited treadmill tests prior to randomization. Eligible patients in each cohort are then randomized to receive a two-hour double-blind intravenous loading dose of CK-1827452 (or placebo) followed by an 18-hour double-blind intravenous infusion of CK-1827452 (or placebo).
In each cohort, patients whose symptom-limited exercise tolerance during the infusion does not deteriorate relative to baseline receive either CK-1827452 or placebo administered orally for seven days, after which tolerability is assessed. CK-1827452 plasma levels are measured before and one hour after the final oral dose.
Patients in the first cohort were randomized in a two-to-one ratio either to CK-1827452 at a dose level intended to target a maximum plasma concentration of 295ng/ml during the infusion period and 184ng/ml during the oral dosing period or to placebo. Patients in the second cohort will be randomized in a two-to-one ratio either to CK-1827452 at a dose level intended to target a plasma concentration of 550ng/ml during the infusion period and 368ng/ml during the oral dosing period or to placebo.
CK-1827452 is the subject of a collaboration and option agreement between Cytokinetics and Amgen. Cytokinetics has also reiterated that it expects to conclude this trial by the end of 2008.