Conditions: Modified Release Oral Formulation Left Ventricular Systolic Dysfunction Chronic Heart Failure History of Chronic Heart Failure Left Ventricular Ejection Fraction Pharmacokinetics Echocardiogram
Keywords: Pharmacokinetics Omecamtiv mecarbil AMG 423 Double-blind Randomized Placebo-controlled Oral forumlation CK-1827452 Cardiac myosin activator
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 544
Healthy volunteers: no

Brief 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.

Arms:
arm 1: Participants received placebo tablets twice a day (BID) for 7 days. arm 2: Participants received 25 mg omecamtiv mecarbil (OM) Matrix F1 (M-F1) tablets twice a day for 7 days. arm 3: Participants received 25 mg omecamtiv mecarbil Matrix F2 (M-F2) tablets twice a day for 7 days. arm 4: Participants received 25 mg omecamtiv mecarbil swellable core technology F2 (SCT-F2) tablets twice a day for 7 days. arm 5: Participants received placebo tablets twice a day for 7 days. arm 6: Participants received 50 mg omecamtiv mecarbil M-F1 tablets twice a day for 7 days. arm 7: Participants received 50 mg omecamtiv mecarbil M-F2 tablets twice a day for 7 days. arm 8: Participants received 50 mg omecamtiv mecarbil SCT-F2 tablets twice a day for 7 days. arm 9: Participants received placebo tablets twice a day for 20 weeks. arm 10: Participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day for 20 weeks. arm 11: All participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day. At week 8 the dose escalated to 50 mg twice a day if the week 2 predose plasma concentration of OM was less than the predefined cutoff of 200 ng/mL.

Interventions: intervention 1: Omecamtiv Mecarbil Matrix F1 Formulation intervention 2: Omecamtiv Mecarbil Matrix F2 Formulation intervention 3: Placebo intervention 4: Omecamtiv Mecarbil Swellable Core Technology F2
Intervention descriptions: intervention 1: Modified release tablets for oral administration intervention 2: Modified release tablets for oral administration intervention 3: Modified release tablets matching to omecamtiv mecarbil intervention 4: Modified release tablets for oral administration

Protocol document: