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

July 25, 2021 updated by: Cytokinetics

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

  • 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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Aichi
      • Kasugai-shi, Aichi, Japan, 486-8510
        • Research Site
      • Kasugai-shi, Aichi, Japan, 487-0016
        • Research Site
      • Nagoya-shi, Aichi, Japan, 454-8509
        • Research Site
    • Chiba
      • Asahi-shi, Chiba, Japan, 289-2511
        • Research Site
      • Chiba-shi, Chiba, Japan, 260-8606
        • Research Site
    • Ehime
      • Imabari-shi, Ehime, Japan, 799-1592
        • Research Site
    • Fukuoka
      • Chikushino-shi, Fukuoka, Japan, 818-8516
        • Research Site
      • Fukuoka-shi, Fukuoka, Japan, 814-0180
        • Research Site
      • Fukuoka-shi, Fukuoka, Japan, 815-8588
        • Research Site
    • Hokkaido
      • Hakodate-shi, Hokkaido, Japan, 041-8512
        • Research Site
      • Sapporo, Hokkaido, Japan, 060-8648
        • Research Site
    • Hyogo
      • Amagasaki-shi, Hyogo, Japan, 660-8550
        • Research Site
      • Kawanishi-shi, Hyogo, Japan, 666-0125
        • Research Site
      • Takarazuka-shi, Hyogo, Japan, 665-0873
        • Research Site
    • Ishikawa
      • Kanazawa-shi, Ishikawa, Japan, 920-8650
        • Research Site
    • Kochi
      • Nankoku-shi, Kochi, Japan, 783-8505
        • Research Site
    • Oita
      • Oita-shi, Oita, Japan, 870-0192
        • Research Site
    • Okayama
      • Okayama-shi, Okayama, Japan, 702-8055
        • Research Site
    • Osaka
      • Kishiwada-shi, Osaka, Japan, 596-8522
        • Research Site
      • Osaka-shi, Osaka, Japan, 532-0003
        • Research Site
      • Osaka-shi, Osaka, Japan, 550-0012
        • Research Site
      • Osaka-shi, Osaka, Japan, 559-0012
        • Research Site
      • Suita-shi, Osaka, Japan, 565-0871
        • Research Site
    • Saga
      • Saga-shi, Saga, Japan, 840-8571
        • Research Site
    • Saitama
      • Saitama-shi, Saitama, Japan, 330-8503
        • Research Site
      • Wako-shi, Saitama, Japan, 351-0102
        • Research Site
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan, 411-8611
        • Research Site
    • Tokyo
      • Chiyoda-ku, Tokyo, Japan, 101-8309
        • Research Site
      • Itabashi-ku, Tokyo, Japan, 173-0015
        • Research Site
      • Itabashi-ku, Tokyo, Japan, 173-8610
        • Research Site
      • Meguro-ku, Tokyo, Japan, 152-8902
        • Research Site
      • Shinagawa-ku, Tokyo, Japan, 141-0001
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo BID
Participants will receive placebo BID.
Drug: 25 mg Omecamtiv Mecarbil
oral tablet
Experimental: 25 mg Omecamtiv Mecarbil BID
Participants will receive 25 mg omecamtiv mecarbil BID.
Drug: Placebo
oral tablet
Experimental: 37.5 mg Omecamtiv Mecarbil BID Target Dose
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.
Drug: 25 mg Omecamtiv Mecarbil
oral tablet
Drug: 37.5 mg Omecamtiv Mecarbil
oral tablet
Experimental: 50 mg Omecamtiv Mecarbil BID Target Dose
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.
Drug: 25 mg Omecamtiv Mecarbil
oral tablet
Drug: 50 mg Omecamtiv Mecarbil
oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time
Time Frame: Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)
Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)
PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)
Time Frame: 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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline at Week 16 in Systolic Ejection Time (SET)
Time Frame: Baseline, Week 16 (Day 112)
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)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From first dose of study drug up to Week 20 (Day 140 + 3 days)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cytokinetics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 14, 2016

Primary Completion (Actual)

April 6, 2017

Study Completion (Actual)

May 8, 2017

Study Registration Dates

First Submitted

February 25, 2016

First Submitted That Met QC Criteria

February 25, 2016

First Posted (Estimate)

March 1, 2016

Study Record Updates

Last Update Posted (Actual)

July 27, 2021

Last Update Submitted That Met QC Criteria

July 25, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20120227

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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