Safety, PK, and Efficacy of Omecamtiv Mecarbil in Japanese Subjects With Heart Failure With Reduced Ejection Fraction

Cytokinetics

Status and phase: Completed; Phase 2

Conditions: Heart Failure With Reduced Ejection Fraction

Treatments: Drug: Placebo; Drug: 37.5 mg Omecamtiv Mecarbil; Drug: 50 mg Omecamtiv Mecarbil; Drug: 25 mg Omecamtiv Mecarbil

Study type: Interventional

Funder types: Industry

Identifiers

NCT02695420

20120227

Details and patient eligibility

About

• To evaluate pharmacokinetics (PK) of omecamtiv mecarbil in Japanese subjects with heart failure (HF) with reduced ejection fraction
• To evaluate the safety and tolerability of oral omecamtiv mecarbil

Full description

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.

Enrollment: 81 patients

Sex: All

Ages: 20 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Japanese male or female ≥ 20 years and ≤ 85 years of age
• History of chronic stable heart failure (HF) with reduced ejection fraction, defined as requiring treatment for HF for a minimum of 4 weeks prior to screening
• Treated for HF with optimal pharmacological therapy
• Left ventricular ejection fraction ≤ 40% at screening

Exclusion criteria

• Severe uncorrected valvular heart disease
• Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease
• Acute myocardial infarction, unstable angina, or persistent angina at rest within 30 days prior to randomization
• Systolic blood pressure (BP) > 160 mmHg or < 90 mmHg, or diastolic BP > 90 mmHg, or heart rate (HR) > 110 beats per minute (bpm) or HR < 50 bpm
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2
• Total bilirubin (TBL) ≥ 2x upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3x ULN Other Exclusion Criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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81 participants in 4 patient groups, including a placebo group

Placebo BID

Placebo Comparator group

Description:

Participants will receive placebo BID.

Treatment:

Drug: 25 mg Omecamtiv Mecarbil

25 mg Omecamtiv Mecarbil BID

Experimental group

Description:

Participants will receive 25 mg omecamtiv mecarbil BID.

Treatment:

Drug: Placebo

37.5 mg Omecamtiv Mecarbil BID Target Dose

Experimental group

Description:

Participants will receive omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK.

Treatment:

Drug: 37.5 mg Omecamtiv Mecarbil

Drug: 25 mg Omecamtiv Mecarbil

50 mg Omecamtiv Mecarbil BID Target Dose

Experimental group

Description:

Participants will receive Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK.

Treatment:

Drug: 50 mg Omecamtiv Mecarbil

Drug: 25 mg Omecamtiv Mecarbil