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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01786512




Registration number
NCT01786512
Ethics application status
Date submitted
18/01/2013
Date registered
8/02/2013
Date last updated
12/08/2021

Titles & IDs
Public title
COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure
Scientific 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
Secondary ID [1] 0 0
2012-000327-40
Secondary ID [2] 0 0
20110151
Universal Trial Number (UTN)
Trial acronym
COSMIC-HF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Modified Release Oral Formulation 0 0
Left Ventricular Systolic Dysfunction 0 0
Chronic Heart Failure 0 0
History of Chronic Heart Failure 0 0
Left Ventricular Ejection Fraction 0 0
Pharmacokinetics 0 0
Echocardiogram 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Omecamtiv Mecarbil Matrix F1 Formulation
Treatment: Drugs - Omecamtiv Mecarbil Matrix F2 Formulation
Treatment: Drugs - Placebo
Treatment: Drugs - Omecamtiv Mecarbil Swellable Core Technology F2

Placebo comparator: Dose-escalation Cohort 1: Placebo - Participants received placebo tablets twice a day (BID) for 7 days.

Experimental: Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F1 - Participants received 25 mg omecamtiv mecarbil (OM) Matrix F1 (M-F1) tablets twice a day for 7 days.

Experimental: Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg M-F2 - Participants received 25 mg omecamtiv mecarbil Matrix F2 (M-F2) tablets twice a day for 7 days.

Experimental: Dose-escalation Cohort 1: Omecamtiv Mecarbil 25 mg SCT-F2 - Participants received 25 mg omecamtiv mecarbil swellable core technology F2 (SCT-F2) tablets twice a day for 7 days.

Placebo comparator: Dose-escalation Cohort 2: Placebo - Participants received placebo tablets twice a day for 7 days.

Experimental: Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F1 - Participants received 50 mg omecamtiv mecarbil M-F1 tablets twice a day for 7 days.

Experimental: Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg M-F2 - Participants received 50 mg omecamtiv mecarbil M-F2 tablets twice a day for 7 days.

Experimental: Dose-escalation Cohort 2: Omecamtiv Mecarbil 50 mg SCT-F2 - Participants received 50 mg omecamtiv mecarbil SCT-F2 tablets twice a day for 7 days.

Placebo comparator: Expansion Phase: Placebo - Participants received placebo tablets twice a day for 20 weeks.

Experimental: Expansion Phase: Omecamtiv Mecarbil 25 mg M-F1 - Participants received 25 mg omecamtiv mecarbil M-F1 tablets twice a day for 20 weeks.

Experimental: Expansion Phase: OM M-F1 PK-based Titration - 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.


Treatment: Drugs: Omecamtiv Mecarbil Matrix F1 Formulation
Modified release tablets for oral administration

Treatment: Drugs: Omecamtiv Mecarbil Matrix F2 Formulation
Modified release tablets for oral administration

Treatment: Drugs: Placebo
Modified release tablets matching to omecamtiv mecarbil

Treatment: Drugs: Omecamtiv Mecarbil Swellable Core Technology F2
Modified release tablets for oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation Phase: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)
Timepoint [1] 0 0
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.
Primary outcome [2] 0 0
Dose Escalation Phase: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil Following the Last Dose (Day 7)
Timepoint [2] 0 0
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.
Primary outcome [3] 0 0
Dose Escalation Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing on Day 7
Timepoint [3] 0 0
Day 7 at predose
Primary outcome [4] 0 0
Dose Escalation Phase: Area Under the Plasma Concentration-time Curve for a Dosing Interval of 12 Hours Post Dose (AUC12) for Omecamtiv Mecarbil
Timepoint [4] 0 0
Day 7 at predose and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose
Primary outcome [5] 0 0
Expansion Phase: Plasma Concentration of Omecamtiv Mecarbil Prior to Dosing
Timepoint [5] 0 0
Predose (before morning dose) at weeks 2, 8, 12, 16, and 20
Primary outcome [6] 0 0
Expansion Phase: Maximum Observed Plasma Concentration of Omecamtiv Mecarbil
Timepoint [6] 0 0
Weeks 2 and 12 at predose and 1, 2, 4, 6, and 8 hours post-dose.
Secondary outcome [1] 0 0
Expansion Phase: Change From Baseline in Systolic Ejection Time (SET) at Week 20
Timepoint [1] 0 0
Baseline and week 20
Secondary outcome [2] 0 0
Expansion Phase: Change From Baseline in Stroke Volume at Week 20
Timepoint [2] 0 0
Baseline and week 20
Secondary outcome [3] 0 0
Expansion Phase: Change From Baseline in Left Ventricular End Systolic Diameter (LVESD) at Week 20
Timepoint [3] 0 0
Baseline and week 20
Secondary outcome [4] 0 0
Expansion Phase: Change From Baseline in Left Ventricular End Diastolic Diameter (LVEDD) at Week 20
Timepoint [4] 0 0
Baseline and week 20
Secondary outcome [5] 0 0
Expansion Phase: Change From Baseline in Heart Rate at Week 20
Timepoint [5] 0 0
Baseline and week 20
Secondary outcome [6] 0 0
Expansion Phase: Change From Baseline in N-terminal Prohormone B-type Natriuretic Peptide (NT-proBNP) at Week 20
Timepoint [6] 0 0
Baseline and week 20
Secondary outcome [7] 0 0
Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events
Timepoint [7] 0 0
From first dose of study drug to 4 weeks after last dose; treatment duration was 7 days in the dose escalation phase.
Secondary outcome [8] 0 0
Expansion Phase: Number of Participants With Treatment-emergent Adverse Events
Timepoint [8] 0 0
From first dose of study drug until 4 weeks after last dose; treatment duration was 20 weeks in the expansion phase.

Eligibility
Key inclusion criteria
* 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)
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/02/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/08/2015
Sample size
Target
Accrual to date
Final
544
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Research Site - Darlinghurst
Recruitment hospital [2] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Maine
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
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Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Belgium
State/province [23] 0 0
Antwerpen
Country [24] 0 0
Belgium
State/province [24] 0 0
Bonheiden
Country [25] 0 0
Belgium
State/province [25] 0 0
Gent
Country [26] 0 0
Belgium
State/province [26] 0 0
Ieper
Country [27] 0 0
Belgium
State/province [27] 0 0
Liege
Country [28] 0 0
Bulgaria
State/province [28] 0 0
Kazanlak
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Pazardzhik
Country [30] 0 0
Bulgaria
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Plovdiv
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Bulgaria
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Sandanski
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Bulgaria
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Sliven
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Bulgaria
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Smolyan
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Bulgaria
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Sofia
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Canada
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Alberta
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Manitoba
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Canada
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Newfoundland and Labrador
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Brno
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Czechia
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Olomouc
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Czechia
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Praha 2
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Czechia
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Praha 4
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Czechia
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Svitavy
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Czechia
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Teplice
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Germany
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Bad Krozingen
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Germany
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Bad Nauheim
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Germany
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Berlin
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Germany
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Dortmund
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Germany
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Greifswald
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Hungary
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Budapest
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Hungary
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Jaszbereny
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Hungary
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Zalaegerszeg
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Italy
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Brescia
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Italy
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Pavia
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Italy
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Verona
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Lithuania
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Kaunas
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Lithuania
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Vilnius
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Netherlands
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Amersfoort
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Netherlands
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Groningen
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Utrecht
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Bialystok
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Klodzko
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Krakow
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Lublin
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Ruda Slaska
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Warszawa
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Wroclaw
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United Kingdom
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Dudley
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Dundee
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Glasgow
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Harrow
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Leicester
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Liverpool
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United Kingdom
State/province [76] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cytokinetics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01786512