Clinical trial NCT02695420: Safety, PK, and Efficacy of Omecamtiv Mecarbil in Japanese Subjects With Heart Failure With Reduced Ejection Fraction
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Omecamtiv Mecarbil in Japanese Subjects With Heart Failure With Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: Heart Failure
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2016-03-01
Enrollment: 81
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: * 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time
timeFrame: Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)
measure: PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)
timeFrame: Week 8 (Day 56) at predose, at 2 hours ±30 minutes; 4 hours ±30 minutes; 6 hours ±30 minutes; 8 hours ±30 minutes after morning dose
Secondary outcomes:
measure: Change From Baseline at Week 16 in Systolic Ejection Time (SET)
timeFrame: Baseline, Week 16 (Day 112)
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to Week 20 (Day 140 + 3 days)
Locations:
city: Kasugai-shi
country: Japan
facility: Research Site
state: Aichi
city: Kasugai-shi
country: Japan
facility: Research Site
state: Aichi
city: Nagoya-shi
country: Japan
facility: Research Site
state: Aichi
city: Asahi-shi
country: Japan
facility: Research Site
state: Chiba
city: Chiba-shi
country: Japan
facility: Research Site
state: Chiba
city: Imabari-shi
country: Japan
facility: Research Site
state: Ehime
city: Chikushino-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Hakodate-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Sapporo
country: Japan
facility: Research Site
state: Hokkaido
city: Amagasaki-shi
country: Japan
facility: Research Site
state: Hyogo
city: Kawanishi-shi
country: Japan
facility: Research Site
state: Hyogo
city: Takarazuka-shi
country: Japan
facility: Research Site
state: Hyogo
city: Kanazawa-shi
country: Japan
facility: Research Site
state: Ishikawa
city: Nankoku-shi
country: Japan
facility: Research Site
state: Kochi
city: Oita-shi
country: Japan
facility: Research Site
state: Oita
city: Okayama-shi
country: Japan
facility: Research Site
state: Okayama
city: Kishiwada-shi
country: Japan
facility: Research Site
state: Osaka
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Suita-shi
country: Japan
facility: Research Site
state: Osaka
city: Saga-shi
country: Japan
facility: Research Site
state: Saga
city: Saitama-shi
country: Japan
facility: Research Site
state: Saitama
city: Wako-shi
country: Japan
facility: Research Site
state: Saitama
city: Sunto-gun
country: Japan
facility: Research Site
state: Shizuoka
city: Chiyoda-ku
country: Japan
facility: Research Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Research Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Research Site
state: Tokyo
city: Meguro-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Research Site
state: Tokyo
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: