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

Heart Failure With Reduced Ejection Fraction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02695420
• Other study ID #: 20120227
• Status: Completed
• Phase: Phase 2
• Start date: April 14, 2016
• Est. completion date: May 8, 2017

Study information

• Verified date: July 2021
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: May 8, 2017
• Est. primary completion date: April 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Drug:
• 25 mg Omecamtiv Mecarbil
oral tablet
• Placebo
oral tablet
• 37.5 mg Omecamtiv Mecarbil
oral tablet
• 50 mg Omecamtiv Mecarbil
oral tablet

Locations

Country	Name	City	State
Japan	Research Site	Amagasaki-shi	Hyogo
Japan	Research Site	Asahi-shi	Chiba
Japan	Research Site	Chiba-shi	Chiba
Japan	Research Site	Chikushino-shi	Fukuoka
Japan	Research Site	Chiyoda-ku	Tokyo
Japan	Research Site	Fukuoka-shi	Fukuoka
Japan	Research Site	Fukuoka-shi	Fukuoka
Japan	Research Site	Hakodate-shi	Hokkaido
Japan	Research Site	Imabari-shi	Ehime
Japan	Research Site	Itabashi-ku	Tokyo
Japan	Research Site	Itabashi-ku	Tokyo
Japan	Research Site	Kanazawa-shi	Ishikawa
Japan	Research Site	Kasugai-shi	Aichi
Japan	Research Site	Kasugai-shi	Aichi
Japan	Research Site	Kawanishi-shi	Hyogo
Japan	Research Site	Kishiwada-shi	Osaka
Japan	Research Site	Meguro-ku	Tokyo
Japan	Research Site	Nagoya-shi	Aichi
Japan	Research Site	Nankoku-shi	Kochi
Japan	Research Site	Oita-shi	Oita
Japan	Research Site	Okayama-shi	Okayama
Japan	Research Site	Osaka-shi	Osaka
Japan	Research Site	Osaka-shi	Osaka
Japan	Research Site	Osaka-shi	Osaka
Japan	Research Site	Saga-shi	Saga
Japan	Research Site	Saitama-shi	Saitama
Japan	Research Site	Sapporo	Hokkaido
Japan	Research Site	Shinagawa-ku	Tokyo
Japan	Research Site	Suita-shi	Osaka
Japan	Research Site	Sunto-gun	Shizuoka
Japan	Research Site	Takarazuka-shi	Hyogo
Japan	Research Site	Wako-shi	Saitama

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is defined as any untoward medical occurrence. Serious AEs are defined as AEs that meets at least 1 of the following serious criteria: fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, other medically important serious event. AEs are graded as: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. TEAEs are defined as events occurring after the first dose of study drug.	From first dose of study drug up to Week 20 (Day 140 + 3 days)
Primary	Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time		Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)
Primary	PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)		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	Change From Baseline at Week 16 in Systolic Ejection Time (SET)	LS mean was from the repeated measures model, which included treatment group, stratification factor (from IVRS), scheduled visit, baseline value, and the interaction of treatment group with scheduled visit as covariates.	Baseline, Week 16 (Day 112)

External Links

•   AmgenTrials clinical trials website