Heart Failure With Reduced Ejection FractionPhase 2NCT02695420

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

A Phase 2 study testing 25 mg Omecamtiv Mecarbil, 37.5 mg Omecamtiv Mecarbil and 50 mg Omecamtiv Mecarbil in people with Heart Failure With Reduced Ejection Fraction, run by Cytokinetics at 32 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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 Read more about this study

Who is it for?: Ages 20 to 85 years
Conditions the study is for: Heart Failure With Reduced Ejection Fraction
What is being tested?: 25 mg Omecamtiv Mecarbil, 37.5 mg Omecamtiv Mecarbil and 50 mg Omecamtiv Mecarbil
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 81 participants
Where: 32 sitesJapan
Study dates: 14 Apr 2016to 8 May 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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 locations and contacts

32 sites in 1 country.

City, postcode or hospital

32 sites in 1 country

Japan32 sites

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

Other trials in Japan

About this study

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

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

Read the 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.

Conditions: Heart Failure With Reduced Ejection Fraction
Being tested: 25 mg Omecamtiv Mecarbil, Placebo, 37.5 mg Omecamtiv Mecarbil, 50 mg Omecamtiv Mecarbil
Keywords: Heart Failure
Medical subject headings: Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

25 mg Omecamtiv MecarbilDrug
oral tablet
PlaceboDrug
oral tablet
37.5 mg Omecamtiv MecarbilDrug
oral tablet
50 mg Omecamtiv MecarbilDrug
oral tablet

Study groups in NCT02695420
Study group	Role	What they receive
Placebo BID	Placebo comparator	Participants will receive placebo BID. Receives: Drug: 25 mg Omecamtiv Mecarbil
25 mg Omecamtiv Mecarbil BID	Experimental	Participants will receive 25 mg omecamtiv mecarbil BID. Receives: Drug: Placebo
37.5 mg Omecamtiv Mecarbil BID Target Dose	Experimental	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. Receives: Drug: 25 mg Omecamtiv Mecarbil; Drug: 37.5 mg Omecamtiv Mecarbil
50 mg Omecamtiv Mecarbil BID Target Dose	Experimental	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. Receives: Drug: 25 mg Omecamtiv Mecarbil; Drug: 50 mg Omecamtiv Mecarbil

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time
Measured: 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)
Measured: 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 (1)

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.
Measured: Baseline, Week 16 (Day 112)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Apr 20168 May 2017

First posted1 Mar 2016 (estimated)
Study start14 Apr 2016
Primary completion6 Apr 2017
Study completion8 May 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 81 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02695420
Sponsor's protocol ID: 20120227
Status last verified: Jul 2021
First submitted: 25 Feb 2016
Last updated: 27 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
Recruiting
Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects With Reduced Ejection Fraction
Heart Failure With Reduced Ejection Fraction (HFrEF)
RecruitingObservational study
Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
Inflammation Biomarkers, Heart Failure

All Heart Failure With Reduced Ejection Fraction trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02695420
Acronym / sponsor ID: 20120227
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: Heart Failure
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 81 participants (actual)
Lead sponsor: CytokineticsIndustry (pharma, biotech, devices)
Study start: 14 Apr 2016 (actual)
Primary completion: 6 Apr 2017 (actual)
Study completion: 8 May 2017 (actual)
First posted: 1 Mar 2016 (estimated)
Results: Posted 31 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Placebo BID	Placebo comparator	Drug: 25 mg Omecamtiv MecarbilParticipants will receive placebo BID.
25 mg Omecamtiv Mecarbil BID	Experimental	Drug: PlaceboParticipants will receive 25 mg omecamtiv mecarbil BID.
37.5 mg Omecamtiv Mecarbil BID Target Dose	Experimental	Drug: 25 mg Omecamtiv Mecarbil, Drug: 37.5 mg Omecamtiv MecarbilParticipants 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.
50 mg Omecamtiv Mecarbil BID Target Dose	Experimental	Drug: 25 mg Omecamtiv Mecarbil, Drug: 50 mg Omecamtiv MecarbilParticipants 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.

Who may qualify

Ages: 20 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
25 mg Omecamtiv Mecarbiloral tablet	Drug	37.5 mg Omecamtiv Mecarbil BID Target Dose, 50 mg Omecamtiv Mecarbil BID Target Dose, Placebo BID
Placebooral tablet	Drug	25 mg Omecamtiv Mecarbil BID
37.5 mg Omecamtiv Mecarbiloral tablet	Drug	37.5 mg Omecamtiv Mecarbil BID Target Dose
50 mg Omecamtiv Mecarbiloral tablet	Drug	50 mg Omecamtiv Mecarbil BID Target Dose

Primary outcome

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)
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

1 secondary outcome

Change From Baseline at Week 16 in Systolic Ejection Time (SET)
Time frame: Baseline, Week 16 (Day 112)

Results and safety

Results posted to the registry on 31 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo BID	21	21
Omecamtiv Mecarbil 25 mg BID	21	20
Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose	19	19
Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose	20	20

Primary outcome: 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). Mean (Standard Deviation). Unit: ng/mL

Measure	Omecamtiv Mecarbil 25 mg BID n = 20	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose n = 18	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n = 20
Week 2	239 (106)	179 (77.1)	208 (61.6)
Week 4	222 (63.5)	196 (44)	209 (61.9)
Week 12	217 (66.1)	228 (56.9)	282 (120)
Week 16	206 (84.5)	244 (67.7)	292 (118)

Population analysed: PK Analysis Set: all randomized participants who received at least one dose of omecamtiv mecarbil and had at least one evaluable omecamtiv mecarbil PK concentration at given time point.

Primary outcome: 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. Mean (Standard Deviation). Unit: hr*ng/mL

Measure	Omecamtiv Mecarbil 25 mg BID n = 9	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose n = 8	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n = 1
Value	1850 (563)	1850 (383)	2360 (465)

Population analysed: PK Analysis Set: all randomized participants who received at least one dose of omecamtiv mecarbil and had at least one evaluable omecamtiv mecarbil PK concentration.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From first dose of study drug up to Week 20 (Day 140 + 3 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo BID	3 of 21 (14.3%)	10 of 21 (47.6%)	0 of 21
Omecamtiv Mecarbil 25 mg BID	4 of 21 (19%)	8 of 21 (38.1%)	1 of 21
Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose	1 of 19 (5.3%)	10 of 19 (52.6%)	0 of 19
Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose	3 of 20 (15%)	11 of 20 (55%)	0 of 20

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
AmgenTrials clinical trials websiteLink provided by the sponsor.

Related trials for Heart Failure With Reduced Ejection Fraction

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
Recruiting
Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects With Reduced Ejection Fraction
Heart Failure With Reduced Ejection Fraction (HFrEF)
RecruitingObservational study
Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
Inflammation Biomarkers, Heart Failure

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

32 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02695420.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2021.