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

Primary Purpose

Heart Failure With Reduced Ejection Fraction

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
25 mg Omecamtiv Mecarbil
Placebo
37.5 mg Omecamtiv Mecarbil
50 mg Omecamtiv Mecarbil
Sponsored by
Cytokinetics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction focused on measuring Heart Failure

Eligibility Criteria

20 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Placebo BID

25 mg Omecamtiv Mecarbil BID

37.5 mg Omecamtiv Mecarbil BID Target Dose

50 mg Omecamtiv Mecarbil BID Target Dose

Arm Description

Participants will receive placebo BID.

Participants will receive 25 mg omecamtiv mecarbil BID.

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.

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.

Outcomes

Primary Outcome Measures

Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time
PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)

Secondary Outcome Measures

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.

Full Information

First Posted
February 25, 2016
Last Updated
July 25, 2021
Sponsor
Cytokinetics
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1. Study Identification

Unique Protocol Identification Number
NCT02695420
Brief Title
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

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
April 14, 2016 (Actual)
Primary Completion Date
April 6, 2017 (Actual)
Study Completion Date
May 8, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytokinetics

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction
Keywords
Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo BID
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo BID.
Arm Title
25 mg Omecamtiv Mecarbil BID
Arm Type
Experimental
Arm Description
Participants will receive 25 mg omecamtiv mecarbil BID.
Arm Title
37.5 mg Omecamtiv Mecarbil BID Target Dose
Arm Type
Experimental
Arm 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.
Arm Title
50 mg Omecamtiv Mecarbil BID Target Dose
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
25 mg Omecamtiv Mecarbil
Intervention Description
oral tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
oral tablet
Intervention Type
Drug
Intervention Name(s)
37.5 mg Omecamtiv Mecarbil
Intervention Description
oral tablet
Intervention Type
Drug
Intervention Name(s)
50 mg Omecamtiv Mecarbil
Intervention Description
oral tablet
Primary Outcome Measure Information:
Title
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)
Title
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
Secondary Outcome Measure Information:
Title
Change From Baseline at Week 16 in Systolic Ejection Time (SET)
Description
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.
Time Frame
Baseline, Week 16 (Day 112)
Other Pre-specified Outcome Measures:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
From first dose of study drug up to Week 20 (Day 140 + 3 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Kasugai-shi
State/Province
Aichi
ZIP/Postal Code
486-8510
Country
Japan
Facility Name
Research Site
City
Kasugai-shi
State/Province
Aichi
ZIP/Postal Code
487-0016
Country
Japan
Facility Name
Research Site
City
Nagoya-shi
State/Province
Aichi
ZIP/Postal Code
454-8509
Country
Japan
Facility Name
Research Site
City
Asahi-shi
State/Province
Chiba
ZIP/Postal Code
289-2511
Country
Japan
Facility Name
Research Site
City
Chiba-shi
State/Province
Chiba
ZIP/Postal Code
260-8606
Country
Japan
Facility Name
Research Site
City
Imabari-shi
State/Province
Ehime
ZIP/Postal Code
799-1592
Country
Japan
Facility Name
Research Site
City
Chikushino-shi
State/Province
Fukuoka
ZIP/Postal Code
818-8516
Country
Japan
Facility Name
Research Site
City
Fukuoka-shi
State/Province
Fukuoka
ZIP/Postal Code
814-0180
Country
Japan
Facility Name
Research Site
City
Fukuoka-shi
State/Province
Fukuoka
ZIP/Postal Code
815-8588
Country
Japan
Facility Name
Research Site
City
Hakodate-shi
State/Province
Hokkaido
ZIP/Postal Code
041-8512
Country
Japan
Facility Name
Research Site
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Research Site
City
Amagasaki-shi
State/Province
Hyogo
ZIP/Postal Code
660-8550
Country
Japan
Facility Name
Research Site
City
Kawanishi-shi
State/Province
Hyogo
ZIP/Postal Code
666-0125
Country
Japan
Facility Name
Research Site
City
Takarazuka-shi
State/Province
Hyogo
ZIP/Postal Code
665-0873
Country
Japan
Facility Name
Research Site
City
Kanazawa-shi
State/Province
Ishikawa
ZIP/Postal Code
920-8650
Country
Japan
Facility Name
Research Site
City
Nankoku-shi
State/Province
Kochi
ZIP/Postal Code
783-8505
Country
Japan
Facility Name
Research Site
City
Oita-shi
State/Province
Oita
ZIP/Postal Code
870-0192
Country
Japan
Facility Name
Research Site
City
Okayama-shi
State/Province
Okayama
ZIP/Postal Code
702-8055
Country
Japan
Facility Name
Research Site
City
Kishiwada-shi
State/Province
Osaka
ZIP/Postal Code
596-8522
Country
Japan
Facility Name
Research Site
City
Osaka-shi
State/Province
Osaka
ZIP/Postal Code
532-0003
Country
Japan
Facility Name
Research Site
City
Osaka-shi
State/Province
Osaka
ZIP/Postal Code
550-0012
Country
Japan
Facility Name
Research Site
City
Osaka-shi
State/Province
Osaka
ZIP/Postal Code
559-0012
Country
Japan
Facility Name
Research Site
City
Suita-shi
State/Province
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Research Site
City
Saga-shi
State/Province
Saga
ZIP/Postal Code
840-8571
Country
Japan
Facility Name
Research Site
City
Saitama-shi
State/Province
Saitama
ZIP/Postal Code
330-8503
Country
Japan
Facility Name
Research Site
City
Wako-shi
State/Province
Saitama
ZIP/Postal Code
351-0102
Country
Japan
Facility Name
Research Site
City
Sunto-gun
State/Province
Shizuoka
ZIP/Postal Code
411-8611
Country
Japan
Facility Name
Research Site
City
Chiyoda-ku
State/Province
Tokyo
ZIP/Postal Code
101-8309
Country
Japan
Facility Name
Research Site
City
Itabashi-ku
State/Province
Tokyo
ZIP/Postal Code
173-0015
Country
Japan
Facility Name
Research Site
City
Itabashi-ku
State/Province
Tokyo
ZIP/Postal Code
173-8610
Country
Japan
Facility Name
Research Site
City
Meguro-ku
State/Province
Tokyo
ZIP/Postal Code
152-8902
Country
Japan
Facility Name
Research Site
City
Shinagawa-ku
State/Province
Tokyo
ZIP/Postal Code
141-0001
Country
Japan

12. IPD Sharing Statement

Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

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

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