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CompletedNCT02695420Updated Jul 27, 2021Results posted

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

A Phase 2 interventional study of 25 mg Omecamtiv Mecarbil and Placebo in Heart Failure With Reduced Ejection Fraction, sponsored by Cytokinetics. Completed at 32 sites in Japan. Open to participants aged 20 Years to 85 Years. Per ClinicalTrials.gov, last updated 2021-07-27.

Sponsored by Cytokinetics · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
81
Allocation
Randomized
Ages
20 Years to 85 Years
Sex
All
01

Study 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 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.

02

Conditions studied

  • Heart Failure With Reduced Ejection Fraction

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Keywords

  • Heart Failure
03

In context

Heart Failure

5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.

This study's enrollment of 81 is above the median of 72 across 3,736 interventional studies indexed under Heart Failure.

Browse Heart Failure studies →

Lead sponsor

Cytokinetics is the lead sponsor of 41 studies on the registry; 3 are open to participants now.

Of its 11 completed or terminated interventional studies of FDA-regulated products, 7 (64%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
81 participants (actual)

Study arms

  • Placebo comparator
    Placebo BID

    Participants will receive placebo BID.

    Drug: 25 mg Omecamtiv Mecarbil

  • Experimental
    25 mg Omecamtiv Mecarbil BID

    Participants will receive 25 mg omecamtiv mecarbil BID.

    Drug: Placebo

  • 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 · Drug: 37.5 mg Omecamtiv Mecarbil

  • 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 · Drug: 50 mg Omecamtiv Mecarbil

Interventions

  • Drug25 mg Omecamtiv Mecarbil

    oral tablet

  • DrugPlacebo

    oral tablet

  • Drug37.5 mg Omecamtiv Mecarbil

    oral tablet

  • Drug50 mg Omecamtiv Mecarbil

    oral tablet

06

What researchers measure

Primary outcomes

  1. 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)

  2. 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 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.

    Time frame: Baseline, Week 16 (Day 112)

Other outcomes

  1. 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.

    Time frame: From first dose of study drug up to Week 20 (Day 140 + 3 days)

07

Results

Posted Jan 31, 2020

Participant flow

Participants were enrolled at 31 research centers in Japan from 14 April 2016 to 16 December 2016.

Participant flow — Overall Study
MilestonePlacebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Started21211920
Completed21201920
Not completed0100
Withdrew: Death0100

Outcome measures

PrimaryPharmacokinetics (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)
Reported as:
Mean · ng/mL
Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time
ng/mLOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Week 2239 ± 106179 ± 77.1208 ± 61.6
Week 4222 ± 63.5196 ± 44209 ± 61.9
Week 12217 ± 66.1228 ± 56.9282 ± 120
Week 16206 ± 84.5244 ± 67.7292 ± 118
PrimaryPK: 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
Reported as:
Mean · hr*ng/mL
PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)
hr*ng/mLOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)1850 ± 5631850 ± 3832360 ± 465
SecondaryChange 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.

Time frame:
Baseline, Week 16 (Day 112)
Reported as:
Least squares mean · msec
Change From Baseline at Week 16 in Systolic Ejection Time (SET)
msecPlacebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Change From Baseline at Week 16 in Systolic Ejection Time (SET)-1.7 ± 4.720.5 ± 4.927.6 ± 5.423.8 ± 5.2
Statistical analysis
  • Placebo BID vs Omecamtiv Mecarbil 25 mg BID · Repeated Measures Model · p = 0.0008 · Treatment difference: 22.1 · 95% CI 9.6 to 34.7
  • Placebo BID vs Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose · Repeated measures model · p = < 0.0001 · Treatment difference: 29.3 · 95% CI 16.3 to 42.3
  • Placebo BID vs Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose · Repeated measures model · p = 0.0002 · Treatment difference: 25.5 · 95% CI 12.6 to 38.4
Other pre-specifiedNumber 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.

Time frame:
From first dose of study drug up to Week 20 (Day 140 + 3 days)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
ParticipantsPlacebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
All TEAEs14101012
Grade >= 2 TEAEs10667
Grade >= 3 TEAEs3412
Grade >= 4 TEAEs0100
Serious AEs3413
TEAEs Leading to Withdrawal of Study Drug0210
Fata Adverse Events0100

Adverse events

Collected over From first dose of study drug up to Week 20 (Day 140 + 3 days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo BID0/21 (0%)3/21 (14.3%)10/21 (47.6%)
Omecamtiv Mecarbil 25 mg BID1/21 (4.8%)4/21 (19%)8/21 (38.1%)
Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose0/19 (0%)1/19 (5.3%)10/19 (52.6%)
Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose0/20 (0%)3/20 (15%)11/20 (55%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventPlacebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
PneumoniaInfections and infestations1/210/211/190/20
Angina pectorisCardiac disorders0/210/210/191/20
Cardiac failureCardiac disorders1/211/210/191/20
Cardiac failure chronicCardiac disorders0/211/210/191/20
Vascular stent restenosisGeneral disorders0/210/210/191/20
Cardiac failure congestiveCardiac disorders0/211/210/190/20
Cardiac ventricular thrombosisCardiac disorders1/210/210/190/20
Cardio-respiratory arrestCardiac disorders0/211/210/190/20
Ventricular fibrillationCardiac disorders0/211/210/190/20
Hepatic function abnormalHepatobiliary disorders0/211/210/190/20
Most frequent other events
Showing 10 of 35
Most frequent other events
EventPlacebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Viral upper respiratory tract infectionInfections and infestations4/211/214/194/20
PeriodontitisInfections and infestations0/211/212/190/20
HypotensionVascular disorders0/210/212/190/20
ArthralgiaMusculoskeletal and connective tissue disorders0/210/210/192/20
DizzinessNervous system disorders1/211/210/192/20
Iron deficiency anaemiaBlood and lymphatic system disorders0/212/210/190/20
InfluenzaInfections and infestations1/212/210/190/20
DehydrationMetabolism and nutrition disorders0/212/210/190/20
DermatitisSkin and subcutaneous tissue disorders0/212/210/190/20
BradycardiaCardiac disorders0/210/211/190/20

Baseline characteristics

Age, Continuous
Age, Continuous(years)Placebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target DoseTotal
Mean64.6 ± 11.566.9 ± 10.363.6 ± 10.866.5 ± 12.265.4 ± 11.1
Sex: Female, Male
Sex: Female, Male(Participants)Placebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target DoseTotal
Female930113
Male1218191968
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Placebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target DoseTotal
Asian2121192081
Other00000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Placebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target DoseTotal
Japanese2121192081
Other00000
Atrial Fibrillation/Flutter at Randomization
Atrial Fibrillation/Flutter at Randomization(participants)Placebo BIDOmecamtiv Mecarbil 25 mg BIDOmecamtiv Mecarbil 25 mg to 37.5 mg BID Target DoseOmecamtiv Mecarbil 25 mg to 50 mg BID Target DoseTotal
Present443415
Absent1717161666
08

Study locations

32 sites
  • Research Site
    Kasugai-shi, Aichi 486-8510, Japan
  • Research Site
    Kasugai-shi, Aichi 487-0016, Japan
  • Research Site
    Nagoya-shi, Aichi 454-8509, Japan
  • Research Site
    Asahi-shi, Chiba 289-2511, Japan
  • Research Site
    Chiba-shi, Chiba 260-8606, Japan
  • Research Site
    Imabari-shi, Ehime 799-1592, Japan
  • Research Site
    Chikushino-shi, Fukuoka 818-8516, Japan
  • Research Site
    Fukuoka-shi, Fukuoka 814-0180, Japan
  • Research Site
    Fukuoka-shi, Fukuoka 815-8588, Japan
  • Research Site
    Hakodate-shi, Hokkaido 041-8512, Japan
  • Research Site
    Sapporo, Hokkaido 060-8648, Japan
  • Research Site
    Amagasaki-shi, Hyogo 660-8550, Japan
  • Research Site
    Kawanishi-shi, Hyogo 666-0125, Japan
  • Research Site
    Takarazuka-shi, Hyogo 665-0873, Japan
  • Research Site
    Kanazawa-shi, Ishikawa 920-8650, Japan
  • Research Site
    Nankoku-shi, Kochi 783-8505, Japan
  • Research Site
    Oita-shi, Oita 870-0192, Japan
  • Research Site
    Okayama-shi, Okayama 702-8055, Japan
  • Research Site
    Kishiwada-shi, Osaka 596-8522, Japan
  • Research Site
    Osaka-shi, Osaka 532-0003, Japan
  • Research Site
    Osaka-shi, Osaka 550-0012, Japan
  • Research Site
    Osaka-shi, Osaka 559-0012, Japan
  • Research Site
    Suita-shi, Osaka 565-0871, Japan
  • Research Site
    Saga-shi, Saga 840-8571, Japan
  • Research Site
    Saitama-shi, Saitama 330-8503, Japan
  • Research Site
    Wako-shi, Saitama 351-0102, Japan
  • Research Site
    Sunto-gun, Shizuoka 411-8611, Japan
  • Research Site
    Chiyoda-ku, Tokyo 101-8309, Japan
  • Research Site
    Itabashi-ku, Tokyo 173-0015, Japan
  • Research Site
    Itabashi-ku, Tokyo 173-8610, Japan
  • Research Site
    Meguro-ku, Tokyo 152-8902, Japan
  • Research Site
    Shinagawa-ku, Tokyo 141-0001, Japan
09

References and documents

Study documents

  • Study protocol · Oct 23, 2015
  • Statistical analysis plan · Feb 29, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 27, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02695420
Lead sponsor
Cytokinetics
Responsible party
Sponsor
First posted
Mar 1, 2016
Start date
Apr 14, 2016
Primary completion
Apr 6, 2017
Completion
May 8, 2017
Results posted
Jan 31, 2020
Last update
Jul 27, 2021

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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