NCT01786512

COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure

A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose Escalation Study to Select and Evaluate an Oral Modified Release Formulation of Omecamtiv Mecarbil in Subjects With Heart Failure and Left Ventricular Systolic Dysfunction

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 544 (actual)
• Sponsor: Cytokinetics · Industry
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The primary objectives of this study are (i) to select an oral modified release (MR) formulation and dose of omecamtiv mecarbil for chronic twice daily (BID) dosing in adults with heart failure and left ventricular systolic dysfunction and (ii) to characterize its pharmacokinetics (PK) over 20 weeks of treatment.

Detailed description

Omecamtiv mecarbil (AMG 423, CK-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. This is a randomized, placebo-controlled, multicenter, phase 2 study, consisting of a dose escalation phase to select 1 of 3 omecamtiv mecarbil oral formulations in 2 dose escalation cohorts, followed by an expansion phase to evaluate 20 weeks of administration of the selected omecamtiv mecarbil formulation at 2 target dose levels, compared with placebo. This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.

Conditions

• Modified Release Oral Formulation
• Left Ventricular Systolic Dysfunction
• Chronic Heart Failure
• History of Chronic Heart Failure
• Left Ventricular Ejection Fraction
• Pharmacokinetics
• Echocardiogram

Interventions

Type	Name	Description
DRUG	Omecamtiv Mecarbil Matrix F1 Formulation	Modified release tablets for oral administration
DRUG	Omecamtiv Mecarbil Matrix F2 Formulation	Modified release tablets for oral administration
DRUG	Placebo	Modified release tablets matching to omecamtiv mecarbil
DRUG	Omecamtiv Mecarbil Swellable Core Technology F2	Modified release tablets for oral administration

Timeline

• Start date: 2013-02-26
• Primary completion: 2015-07-22
• Completion: 2015-08-19
• First posted: 2013-02-08
• Last updated: 2021-08-12
• Results posted: 2021-05-17

Locations

101 sites across 13 countries: United States, Australia, Belgium, Bulgaria, Canada, Czechia, Germany, Hungary, Italy, Lithuania, Netherlands, Poland, United Kingdom