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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT01786512
Ethics application status
Date submitted
18/01/2013
Date registered
8/02/2013
Date last updated
16/08/2017

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 HF and Left Ventricular Systolic Dysfunction
Secondary ID [1] 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Omecamtiv Mecarbil
Treatment: Drugs - Omecamtiv Mecarbil
Treatment: Drugs - Placebo
Treatment: Drugs - Omecamtiv Mecarbil
Treatment: Drugs - Omecamtiv Mecarbil

Experimental: Omecamtiv mecarbil -

Placebo Comparator: Placebo -


Treatment: Drugs: Omecamtiv Mecarbil
Oral omecamtiv mecarbil dose of 25-mg BID for 7 days

Treatment: Drugs: Omecamtiv Mecarbil
Oral omecamtiv mecardbil dose of 50-mg BID for 7 days.

Treatment: Drugs: Placebo
Placebo

Treatment: Drugs: Omecamtiv Mecarbil
Oral omecamtiv mecarbil dose of 25-mg BID for 20 weeks.

Treatment: Drugs: Omecamtiv Mecarbil
Oral omecamtiv mecarbil dose of 25 mg BID for 8 weeks followed by 50-mg BID for 12 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation - Characterize Pharmacokinetics - Cmax - Maximum Observed Plasma Concentration (Cmax)
Timepoint [1] 0 0
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 96, 120 hours after first dose; 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 168 hours following dose on day 7
Primary outcome [2] 0 0
Dose Escalation - Characterize Pharmacokinetics -Cmin - Minimum Observed Concentration (Cmin)
Timepoint [2] 0 0
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 96, 120 hours after first dose; 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 168 hours following dose on day 7
Primary outcome [3] 0 0
Dose Escalation - Characterize Pharmacokinetics-Tmax - Time to Reach Maximum Plasma Concentration (Tmax)
Timepoint [3] 0 0
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 96, 120 hours after first dose; 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 168 hours following dose on day 7
Primary outcome [4] 0 0
Dose Escalation - Characterize Pharmacokinetics - AUC12h - Area under the curve until 12 hours after investigational product (IP) administration (AUC12h)
Timepoint [4] 0 0
0, 0.5, 1, 2, 3, 4, 6, 8, 12 hours after first dose; 0, 0.5, 1, 2, 3, 4, 6, 8, 12 hours following dose on day 7
Primary outcome [5] 0 0
Dose Expansion - Characterize Pharmacokinetics - Cmax - Maximum Observed Plasma Concentration (Cmax)
Timepoint [5] 0 0
predose, predose, 1 , 2, 4, 6, and 8 hours after morning dose on weeks 2 and 12; predose, between 1-4 hours post dose on week 20
Primary outcome [6] 0 0
Dose Expansion - Characterize Pharmacokinetics - Cpredose - Concentration prior to IP administration (Cpredose)
Timepoint [6] 0 0
predose before morning dose on Day1, weeks 2, 8 , 12, 16 and 20
Secondary outcome [1] 0 0
Systolic Ejection Time(SET) (msec) - Changes from baseline in Systolic Ejection Time (SET)
Timepoint [1] 0 0
baseline and 20 weeks
Secondary outcome [2] 0 0
Left Ventricular End-Systolic Diameter (LVESD) (cm) - Changes from baseline in Left Ventricular End-Systolic Diameter (LVESD)
Timepoint [2] 0 0
baseline and 20 weeks
Secondary outcome [3] 0 0
Left Ventricular End-Diastolic Diameter (LVEDD) (cm) - Changes from baseline in Left Ventricular End-Diastolic Diameter (LVEDD)
Timepoint [3] 0 0
baseline and 20 weeks
Secondary outcome [4] 0 0
Heart Rate (beats per minute) - Changes from baseline in heart rate
Timepoint [4] 0 0
baseline and 20 weeks
Secondary outcome [5] 0 0
Stroke Volume (ml) - Changes from baseline in Stroke Volume
Timepoint [5] 0 0
baseline and 20 weeks
Secondary outcome [6] 0 0
Effect of omecamtiv mecarbil on NT-proBNP (pg/mL) - To evaluate the effect of 12 weeks of oral dosing with omecamtiv mecarbil on Nterminal pro-B-type natriuretic peptide (NT-proBNP)
Timepoint [6] 0 0
baseline and 20 weeks
Secondary outcome [7] 0 0
Dose Escalation - Safety and tolerability of oral omecamtiv mecarbil - Subject incidence of adverse events from baseline to 35 days (end of study)
Timepoint [7] 0 0
baseline to 35 days
Secondary outcome [8] 0 0
Dose Expansion - Safety and tolerability of oral omecamtiv mecarbil - Subject incidence of adverse events from baseline to week 24 (end of study)
Timepoint [8] 0 0
baseline to 24 weeks

Eligibility
Key inclusion criteria
- History of chronic 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 fragment BNP (NT-proBNP)
Minimum age
18 Years
Maximum age
85 Years
Gender
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 BP > 160 mmHg or < 90 mmHg or diastolic BP > 90 mmHg

- TBL = 2x ULN; AST or ALT = 3x ULN

- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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United States of America
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Delaware
Country [5] 0 0
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Florida
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Georgia
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Illinois
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Maine
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Maryland
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Michigan
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Minnesota
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Missouri
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Nevada
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New York
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North Carolina
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Oklahoma
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Oregon
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South Carolina
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Tennessee
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Texas
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Washington
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Wisconsin
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Belgium
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Antwerpen
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Belgium
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Bonheiden
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Belgium
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Gent
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Belgium
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Ieper
Country [27] 0 0
Belgium
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Liege
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Bulgaria
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Kazanlak
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Pazardzhik
Country [30] 0 0
Bulgaria
State/province [30] 0 0
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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Alberta
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Manitoba
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Nova Scotia
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Ontario
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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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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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Netherlands
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Utrecht
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Poland
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Bialystok
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Poland
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Klodzko
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Poland
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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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United Kingdom
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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
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Cytokinetics
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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 subjects
with HF and left ventricular systolic dysfunction and (ii) to characterize its
pharmacokinetics (PK) over 20 weeks of treatment.
Trial website
https://clinicaltrials.gov/show/NCT01786512
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

Summary results
Other publications