Modified Release Oral FormulationPhase 2COSMIC-HFNCT01786512
COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure
A Phase 2 study testing Omecamtiv Mecarbil Matrix F1 Formulation, Omecamtiv Mecarbil Matrix F2 Formulation and Omecamtiv Mecarbil Swellable Core Technology F2 in people with Modified Release Oral Formulation and Left Ventricular Systolic Dysfunction, run by Cytokinetics at 101 sites in 13 countries.
Trial summary
The primary objectives of this study are (i) to select an oral modified release (MR) formulation and dose of omecamtiv mecarbil for chronic twice daily (BID) dosing in adults with heart failure and left ventricular systolic dysfunction and (ii) to characterize its pharmacokinetics (PK) over 20 weeks of treatment. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Modified Release Oral Formulation, Left Ventricular Systolic Dysfunction, Chronic Heart Failure
- What is being tested?
- Omecamtiv Mecarbil Matrix F1 Formulation, Omecamtiv Mecarbil Matrix F2 Formulation and Omecamtiv Mecarbil Swellable Core Technology F2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 544 participants
- Where
- 101 sitesin 13 countries
- Study dates
- 26 Feb 2013to 19 Aug 2015
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of chronic heart failure (HF), defined as requiring treatment for HF for a minimum of 4 weeks prior to screening
- Treated with stable, optimal pharmacological therapy for ≥ 4 weeks
- History of left ventricular ejection fraction (LVEF) ≤ 40%
- Elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP)
Who cannot join
- Severe uncorrected valvular heart disease
- Hospitalization within 30 days prior to enrollment
- 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 > 160 mmHg or < 90 mmHg or diastolic blood pressure > 90 mmHg
- Total bilirubin ≥ 2 x upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 x ULN
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2
Trial locations and contacts
101 sites in 13 countries.
101 sites in 13 countries
United States38 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Atlantis, Florida, 33462
Research Site
Auburn, Maine, 04210
Research Site
Aventura, Florida, 33180
Research Site
Baltimore, Maryland, 21201
Research Site
Chapel Hill, North Carolina, 27599
Research Site
Chicago, Illinois, 60612
Research Site
Clearwater, Florida, 33756
Research Site
Cortlandt Manor, New York, 10567
Research Site
Costa Mesa, California, 92626
Research Site
Danbury, Connecticut, 06810
Research Site
Detroit, Michigan, 48202
Research Site
Durham, North Carolina, 27705
Research Site
Fresno, California, 93721
Research Site
Greenville, South Carolina, 29605
Research Site
Houston, Texas, 77030
Research Site
Inglewood, California, 90301
Research Site
La Jolla, California, 92037
Research Site
Las Vegas, Nevada, 89128
Research Site
Los Angeles, California, 90033
Research Site
Macon, Georgia, 31201
Research Site
Madison, Wisconsin, 53792
Research Site
Miami, Florida, 33136
Research Site
Minneapolis, Minnesota, 55415
Research Site
Minneapolis, Minnesota, 55417
Research Site
Mobile, Alabama, 36608
Research Site
Nashville, Tennessee, 37232-8802
Research Site
Newark, Delaware, 19718
Research Site
Oklahoma City, Oklahoma, 73120
Research Site
Petoskey, Michigan, 49770
Research Site
Portland, Oregon, 97239
Research Site
Seattle, Washington, 98195
Research Site
St Louis, Missouri, 63110
Research Site
Tampa, Florida, 33606
Research Site
The Bronx, New York, 10467
Research Site
Thousand Oaks, California, 91360
Research Site
Tullahoma, Tennessee, 37388
Research Site
Tustin, California, 92780
Canada9 sites
Research Site
Edmonton, Alberta, T6G 2B7
Research Site
Halifax, Nova Scotia, B3H 3A7
Research Site
Montreal, Quebec, H3G 1A4
Research Site
Ottawa, Ontario, K1Y 4W7
Research Site
Québec, Quebec, G1V 4G5
Research Site
Sherbrooke, Quebec, J1G 2E8
Research Site
St. John's, Newfoundland and Labrador, A1B 3V6
Research Site
Trois-Rivières, Quebec, G8T 7A1
Research Site
Winnipeg, Manitoba, R2H 2A6
Poland8 sites
Research Site
Bialystok, 15-276
Research Site
Kłodzko, 57-300
Research Site
Krakow, 31-202
Research Site
Krakow, 31-501
Research Site
Lublin, 20-954
Research Site
Ruda Śląska, 41-703
Research Site
Warsaw, 04-256
Research Site
Wroclaw, 50-981
Bulgaria7 sites
Research Site
Kazanlak, 6100
Research Site
Pazardzhik, 4700
Research Site
Plovdiv, 4002
Research Site
Sandanski, 2800
Research Site
Sliven, 8800
Research Site
Smolyan, 4400
Research Site
Sofia, 1527
Czechia7 sites
Research Site
Brno, 625 00
Research Site
Brno, 636 00
Research Site
Olomouc, 771 11
Research Site
Prague, 128 08
Research Site
Prague, 140 21
Research Site
Svitavy, 568 25
Research Site
Teplice, 415 29
United Kingdom7 sites
Research Site
Dudley, DY1 2HQ
Research Site
Dundee, DD1 9SY
Research Site
Glasgow, G11 6NT
Research Site
Harrow, HA1 3UJ
Research Site
Leicester, LE3 9QP
Research Site
Liverpool, L14 3PE
Research Site
London, EC1M 6BQ
Belgium5 sites
Research Site
Antwerp, 2020
Research Site
Bonheiden, 2820
Research Site
Ghent, 9000
Research Site
Ieper, 8900
Research Site
Liège, 4000
Germany5 sites
Research Site
Bad Krozingen, 79189
Research Site
Bad Nauheim, 61231
Research Site
Berlin, 13353
Research Site
Dortmund, 44137
Research Site
Greifswald, 17475
Hungary5 sites
Research Site
Budapest, 1027
Research Site
Budapest, 1125
Research Site
Budapest, 1135
Research Site
Jászberény, 5100
Research Site
Zalaegerszeg, 8900
Italy3 sites
Research Site
Brescia, 25125
Research Site
Pavia, 27100
Research Site
Verona, 37134
Netherlands3 sites
Research Site
Amersfoort, 3813 TZ
Research Site
Groningen, 9713 GZ
Research Site
Utrecht, 3584 CX
Australia2 sites
Research Site
Darlinghurst, New South Wales, 2010
Research Site
Nedlands, Western Australia, 6009
About this study
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose Escalation Study to Select and Evaluate an Oral Modified Release Formulation of Omecamtiv Mecarbil in Subjects With Heart Failure and Left Ventricular Systolic Dysfunction
The primary objectives of this study are (i) to select an oral modified release (MR) formulation and dose of omecamtiv mecarbil for chronic twice daily (BID) dosing in adults with heart failure and left ventricular systolic dysfunction and (ii) to characterize its pharmacokinetics (PK) over 20 weeks of treatment.
Read the detailed description
Omecamtiv mecarbil (AMG 423, CK-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. This is a randomized, placebo-controlled, multicenter, phase 2 study, consisting of a dose escalation phase to select 1 of 3 omecamtiv mecarbil oral formulations in 2 dose escalation cohorts, followed by an expansion phase to evaluate 20 weeks of administration of the selected omecamtiv mecarbil formulation at 2 target dose levels, compared with placebo.
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
- Modified Release Oral Formulation, Left Ventricular Systolic Dysfunction, Chronic Heart Failure, History of Chronic Heart Failure, Left Ventricular Ejection Fraction, Pharmacokinetics
- Being tested
- Omecamtiv Mecarbil Matrix F1 Formulation, Omecamtiv Mecarbil Matrix F2 Formulation, Placebo, Omecamtiv Mecarbil Swellable Core Technology F2
- Keywords
- Pharmacokinetics, Omecamtiv mecarbil, AMG 423, Double-blind, Randomized, Placebo-controlled, Oral forumlation, CK-1827452, Cardiac myosin activator
- Medical subject headings
- Ventricular Dysfunction, Left
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omecamtiv Mecarbil Matrix F1 FormulationDrug
Also called AMG 423, CK-1827452
Modified release tablets for oral administration
Omecamtiv Mecarbil Matrix F2 FormulationDrug
Also called AMG 423, CK-1827452
Modified release tablets for oral administration
PlaceboDrug
Modified release tablets matching to omecamtiv mecarbil
Omecamtiv Mecarbil Swellable Core Technology F2Drug
Also called AMG 423, CK-1827452
Modified release tablets for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Dose-escalation Cohort 1: Placebo | Placebo comparator | Participants received placebo tablets twice a day (BID) for 7 days. Receives: Drug: Placebo |
| Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F1 | Experimental | Participants received 25 mg omecamtiv mecarbil (OM) Matrix F1 (M-F1) tablets twice a day for 7 days. Receives: Drug: Omecamtiv Mecarbil Matrix F1 Formulation |
| Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F2 | Experimental | Participants received 25 mg omecamtiv mecarbil Matrix F2 (M-F2) tablets twice a day for 7 days. Receives: Drug: Omecamtiv Mecarbil Matrix F2 Formulation |
| Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F2 | Experimental | Participants received 25 mg omecamtiv mecarbil swellable core technology F2 (SCT-F2) tablets twice a day for 7 days. Receives: Drug: Omecamtiv Mecarbil Swellable Core Technology F2 |
| Dose-escalation Cohort 2: Placebo | Placebo comparator | Participants received placebo tablets twice a day for 7 days. Receives: Drug: Placebo |
| Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F1 | Experimental | Participants received 50 mg omecamtiv mecarbil M-F1 tablets twice a day for 7 days. Receives: Drug: Omecamtiv Mecarbil Matrix F1 Formulation |
| Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F2 | Experimental | Participants received 50 mg omecamtiv mecarbil M-F2 tablets twice a day for 7 days. Receives: Drug: Omecamtiv Mecarbil Matrix F2 Formulation |
| Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F2 | Experimental | Participants received 50 mg omecamtiv mecarbil SCT-F2 tablets twice a day for 7 days. Receives: Drug: Omecamtiv Mecarbil Swellable Core Technology F2 |
| Expansion Phase: Placebo | Placebo comparator | Participants received placebo tablets twice a day for 20 weeks. Receives: Drug: Placebo |
| Expansion Phase: Omecamtiv Mecarbil 25 mg M-F1 | Experimental | Participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day for 20 weeks. Receives: Drug: Omecamtiv Mecarbil Matrix F1 Formulation |
| Expansion Phase: OM M-F1 PK-based Titration | Experimental | All participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day. At week 8 the dose escalated to 50 mg twice a day if the week 2 predose plasma concentration of OM was less than the predefined cutoff of 200 ng/mL. Receives: Drug: Omecamtiv Mecarbil Matrix F1 Formulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation Phase: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)
Measured: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.
Dose Escalation Phase: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)
Measured: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.
Dose Escalation Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing on Day 7
Measured: Day 7 at predose
Dose Escalation Phase: Area Under the Plasma Concentration-time Curve for a Dosing Interval of 12 Hours Post Dose (AUC12) for Omecamtiv Mecarbil
Measured: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose
Expansion Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing
Measured: Predose (before morning dose) at weeks 2, 8, 12, 16, and 20
Expansion Phase: Maximum Observed Plasma Concentration of Omecamtiv Mecarbil
Measured: Weeks 2 and 12 at predose and 1, 2, 4, 6, and 8 hours post-dose.
Secondary outcomes (8)
Expansion Phase: Change From Baseline in Systolic Ejection Time (SET) at Week 20
Systolic ejection time was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.
Measured: Baseline and week 20
Expansion Phase: Change From Baseline in Stroke Volume at Week 20
Stroke volume was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.
Measured: Baseline and week 20
Expansion Phase: Change From Baseline in Left Ventricular End Systolic Diameter (LVESD) at Week 20
LVESD was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.
Measured: Baseline and week 20
Expansion Phase: Change From Baseline in Left Ventricular End Diastolic Diameter (LVEDD) at Week 20
LVEDD was measured using echocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.
Measured: Baseline and week 20
Expansion Phase: Change From Baseline in Heart Rate at Week 20
Heart rate was measured using electrocardiography. Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.
Measured: Baseline and week 20
Expansion Phase: Change From Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) at Week 20
Least squares means are from a repeated measures model including treatment group, stratification factor, scheduled visit, interaction of treatment with scheduled visit and the baseline value as covariates.
Measured: Baseline and week 20
Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a preexisting medical condition. The event does not necessarily have a causal relationship with study treatment. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events.
Each adverse event was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, and Grade 4 = life-threatening AE.
A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria:
- fatal
- life threatening
- required in-patient hospitalization or prolongation of existing hospitalization
- resulted in persistent or significant disability/incapacity
- congenital anomaly/birth defect
- other medically important serious event
Measured: From first dose of study drug to 4 weeks after last dose; treatment duration was 7 days in the dose escalation phase.
Expansion Phase: Number of Participants With Treatment-emergent Adverse Events
An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a preexisting medical condition. The event does not necessarily have a causal relationship with study treatment. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events.
Each adverse event was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, and Grade 4 = life-threatening AE.
A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria:
- fatal
- life threatening
- required in-patient hospitalization or prolongation of existing hospitalization
- resulted in persistent or significant disability/incapacity
- congenital anomaly/birth defect
- other medically important serious event
Measured: From first dose of study drug until 4 weeks after last dose; treatment duration was 20 weeks in the expansion phase.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2013 (estimated)
- Study start26 Feb 2013
- Primary completion22 Jul 2015
- Study completion19 Aug 2015
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.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Modified Release Oral FormulationStudies 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
- 544 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01786512
- Sponsor's protocol ID
- 20110151
- Other IDs
- 2012-000327-40
- Acronym
- COSMIC-HF
- Status last verified
- Jul 2021
- First submitted
- 18 Jan 2013
- Last updated
- 12 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Teerlink JR, Felker GM, McMurray JJ, Solomon SD, Adams KF Jr, Cleland JG, Ezekowitz JA, Goudev A, Macdonald P, Metra M, Mitrovic V, Ponikowski P, Serpytis P, Spinar J, Tomcsanyi J, Vandekerckhove HJ, Voors AA, Monsalvo ML, Johnston J, Malik FI, Honarpour N; COSMIC-HF Investigators. Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet. 2016 Dec 10;388(10062):2895-2903. doi: 10.1016/S0140-6736(16)32049-9. Epub 2016 Dec 1.
PubMed 27914656Biering-Sorensen T, Minamisawa M, Liu J, Claggett B, Papolos AI, Felker GM, McMurray JJV, Legg JC, Malik FI, Honarpour N, Kurtz CE, Teerlink JR, Solomon SD. The effect of the cardiac myosin activator, omecamtiv mecarbil, on right ventricular structure and function in chronic systolic heart failure (COSMIC-HF). Eur J Heart Fail. 2021 Jun;23(6):1052-1056. doi: 10.1002/ejhf.2181. Epub 2021 May 5. No abstract available.
PubMed 33826209Biering-Sorensen T, Minamisawa M, Claggett B, Liu J, Felker GM, McMurray JJV, Malik FI, Abbasi S, Kurtz CE, Teerlink JR, Solomon SD. Cardiac Myosin Activator Omecamtiv Mecarbil Improves Left Ventricular Myocardial Deformation in Chronic Heart Failure: The COSMIC-HF Trial. Circ Heart Fail. 2020 Dec;13(12):e008007. doi: 10.1161/CIRCHEARTFAILURE.120.008007. Epub 2020 Nov 12. No abstract available.
PubMed 33176443Felker GM, Solomon SD, McMurray JJV, Cleland JGF, Abbasi SA, Malik FI, Zhang H, Globe G, Teerlink JR; COSMIC-HF Investigators. Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure: Results From the COSMIC-HF Study. Circ Heart Fail. 2020 Dec;13(12):e007814. doi: 10.1161/CIRCHEARTFAILURE.120.007814. Epub 2020 Nov 12.
PubMed 33176437
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose Escalation Study to Select and Evaluate an Oral Modified Release Formulation of Omecamtiv Mecarbil in Subjects With Heart Failure and Left Ventricular Systolic Dysfunction
- ClinicalTrials.gov ID
- NCT01786512
- Acronym / sponsor ID
- COSMIC-HF / 20110151
- Conditions
- Modified Release Oral Formulation, Left Ventricular Systolic Dysfunction, Chronic Heart Failure, History of Chronic Heart Failure, Left Ventricular Ejection Fraction, Pharmacokinetics
- Keywords
- Pharmacokinetics, Omecamtiv mecarbil, AMG 423, Double-blind, Randomized, Placebo-controlled, Oral forumlation, CK-1827452
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 544 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Study start
- 26 Feb 2013 (actual)
- Primary completion
- 22 Jul 2015 (actual)
- Study completion
- 19 Aug 2015 (actual)
- First posted
- 8 Feb 2013 (estimated)
- Results
- Posted 17 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objectives of this study are (i) to select an oral modified release (MR) formulation and dose of omecamtiv mecarbil for chronic twice daily (BID) dosing in adults with heart failure and left ventricular systolic dysfunction and (ii) to characterize its pharmacokinetics (PK) over 20 weeks of treatment.
Detailed description
Omecamtiv mecarbil (AMG 423, CK-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. This is a randomized, placebo-controlled, multicenter, phase 2 study, consisting of a dose escalation phase to select 1 of 3 omecamtiv mecarbil oral formulations in 2 dose escalation cohorts, followed by an expansion phase to evaluate 20 weeks of administration of the selected omecamtiv mecarbil formulation at 2 target dose levels, compared with placebo.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation Cohort 1: Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo tablets twice a day (BID) for 7 days. |
| Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F1 | Experimental | Drug: Omecamtiv Mecarbil Matrix F1 FormulationParticipants received 25 mg omecamtiv mecarbil (OM) Matrix F1 (M-F1) tablets twice a day for 7 days. |
| Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F2 | Experimental | Drug: Omecamtiv Mecarbil Matrix F2 FormulationParticipants received 25 mg omecamtiv mecarbil Matrix F2 (M-F2) tablets twice a day for 7 days. |
| Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F2 | Experimental | Drug: Omecamtiv Mecarbil Swellable Core Technology F2Participants received 25 mg omecamtiv mecarbil swellable core technology F2 (SCT-F2) tablets twice a day for 7 days. |
| Dose-escalation Cohort 2: Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo tablets twice a day for 7 days. |
| Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F1 | Experimental | Drug: Omecamtiv Mecarbil Matrix F1 FormulationParticipants received 50 mg omecamtiv mecarbil M-F1 tablets twice a day for 7 days. |
| Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F2 | Experimental | Drug: Omecamtiv Mecarbil Matrix F2 FormulationParticipants received 50 mg omecamtiv mecarbil M-F2 tablets twice a day for 7 days. |
| Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F2 | Experimental | Drug: Omecamtiv Mecarbil Swellable Core Technology F2Participants received 50 mg omecamtiv mecarbil SCT-F2 tablets twice a day for 7 days. |
| Expansion Phase: Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo tablets twice a day for 20 weeks. |
| Expansion Phase: Omecamtiv Mecarbil 25 mg M-F1 | Experimental | Drug: Omecamtiv Mecarbil Matrix F1 FormulationParticipants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day for 20 weeks. |
| Expansion Phase: OM M-F1 PK-based Titration | Experimental | Drug: Omecamtiv Mecarbil Matrix F1 FormulationAll participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day. At week 8 the dose escalated to 50 mg twice a day if the week 2 predose plasma concentration of OM was less than the predefined cutoff of 200 ng/mL. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- History of chronic heart failure (HF), defined as requiring treatment for HF for a minimum of 4 weeks prior to screening
- Treated with stable, optimal pharmacological therapy for ≥ 4 weeks
- History of left ventricular ejection fraction (LVEF) ≤ 40%
- Elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP)
Key exclusion criteria (7 listed)
- Severe uncorrected valvular heart disease
- Hospitalization within 30 days prior to enrollment
- 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 > 160 mmHg or < 90 mmHg or diastolic blood pressure > 90 mmHg
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 |
|---|---|---|
| Omecamtiv Mecarbil Matrix F1 FormulationAlso: AMG 423, CK-1827452Modified release tablets for oral administration | Drug | Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F1, Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F1, Expansion Phase: OM M-F1 PK-based Titration, Expansion Phase: Omecamtiv Mecarbil 25 mg M-F1 |
| Omecamtiv Mecarbil Matrix F2 FormulationAlso: AMG 423, CK-1827452Modified release tablets for oral administration | Drug | Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F2, Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F2 |
| PlaceboModified release tablets matching to omecamtiv mecarbil | Drug | Dose-escalation Cohort 1: Placebo, Dose-escalation Cohort 2: Placebo, Expansion Phase: Placebo |
| Omecamtiv Mecarbil Swellable Core Technology F2Also: AMG 423, CK-1827452Modified release tablets for oral administration | Drug | Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F2, Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F2 |
Primary outcome
Dose Escalation Phase: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)
Time frame: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.
Dose Escalation Phase: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)
Time frame: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.
Dose Escalation Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing on Day 7
Time frame: Day 7 at predose
Dose Escalation Phase: Area Under the Plasma Concentration-time Curve for a Dosing Interval of 12 Hours Post Dose (AUC12) for Omecamtiv Mecarbil
Time frame: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose
Expansion Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing
Time frame: Predose (before morning dose) at weeks 2, 8, 12, 16, and 20
Expansion Phase: Maximum Observed Plasma Concentration of Omecamtiv Mecarbil
Time frame: Weeks 2 and 12 at predose and 1, 2, 4, 6, and 8 hours post-dose.
8 secondary outcomes
Expansion Phase: Change From Baseline in Systolic Ejection Time (SET) at Week 20
Time frame: Baseline and week 20
Expansion Phase: Change From Baseline in Stroke Volume at Week 20
Time frame: Baseline and week 20
Expansion Phase: Change From Baseline in Left Ventricular End Systolic Diameter (LVESD) at Week 20
Time frame: Baseline and week 20
Expansion Phase: Change From Baseline in Left Ventricular End Diastolic Diameter (LVEDD) at Week 20
Time frame: Baseline and week 20
Expansion Phase: Change From Baseline in Heart Rate at Week 20
Time frame: Baseline and week 20
Expansion Phase: Change From Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) at Week 20
Time frame: Baseline and week 20
Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events
Time frame: From first dose of study drug to 4 weeks after last dose; treatment duration was 7 days in the dose escalation phase.
Expansion Phase: Number of Participants With Treatment-emergent Adverse Events
Time frame: From first dose of study drug until 4 weeks after last dose; treatment duration was 20 weeks in the expansion phase.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27914656Teerlink JR, Felker GM, McMurray JJ, Solomon SD, Adams KF Jr, Cleland JG, Ezekowitz JA, Goudev A, Macdonald P, Metra M, Mitrovic V, Ponikowski P, Serpytis P, Spinar J, Tomcsanyi J, Vandekerckhove HJ, Voors AA, Monsalvo ML, Johnston J, Malik FI, Honarpour N; COSMIC-HF Investigators. Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet. 2016 Dec 10;388(10062):2895-2903. doi: 10.1016/S0140-6736(16)32049-9. Epub 2016 Dec 1.
- Derived from this study: PubMed 33826209Biering-Sorensen T, Minamisawa M, Liu J, Claggett B, Papolos AI, Felker GM, McMurray JJV, Legg JC, Malik FI, Honarpour N, Kurtz CE, Teerlink JR, Solomon SD. The effect of the cardiac myosin activator, omecamtiv mecarbil, on right ventricular structure and function in chronic systolic heart failure (COSMIC-HF). Eur J Heart Fail. 2021 Jun;23(6):1052-1056. doi: 10.1002/ejhf.2181. Epub 2021 May 5. No abstract available.
- Derived from this study: PubMed 33176443Biering-Sorensen T, Minamisawa M, Claggett B, Liu J, Felker GM, McMurray JJV, Malik FI, Abbasi S, Kurtz CE, Teerlink JR, Solomon SD. Cardiac Myosin Activator Omecamtiv Mecarbil Improves Left Ventricular Myocardial Deformation in Chronic Heart Failure: The COSMIC-HF Trial. Circ Heart Fail. 2020 Dec;13(12):e008007. doi: 10.1161/CIRCHEARTFAILURE.120.008007. Epub 2020 Nov 12. No abstract available.
- Derived from this study: PubMed 33176437Felker GM, Solomon SD, McMurray JJV, Cleland JGF, Abbasi SA, Malik FI, Zhang H, Globe G, Teerlink JR; COSMIC-HF Investigators. Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure: Results From the COSMIC-HF Study. Circ Heart Fail. 2020 Dec;13(12):e007814. doi: 10.1161/CIRCHEARTFAILURE.120.007814. Epub 2020 Nov 12.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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
101 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omecamtiv Mecarbil Matrix F1 Formulation, Omecamtiv Mecarbil Matrix F2 Formulation and Omecamtiv Mecarbil Swellable Core Technology F2 in people with Modified Release Oral Formulation and Left Ventricular Systolic Dysfunction, run by Cytokinetics at 101 sites in 13 countries.
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 7 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 12 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 101 sites in United States, Canada, Poland, Bulgaria, Czechia and 8 more countries. 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 17 May 2021). 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?
Dose Escalation Phase: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7) (time frame: Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 days post-dose.). The study lists 6 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 NCT01786512, which also lists 4 linked publications.
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 12 Aug 2021; AzTrials last refreshed its copy on 7 Nov 2026.