Trial record 4 of 6 for:    omecamtiv

COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure.

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Amgen
Sponsor:
Collaborator:
Cytokinetics
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01786512
First received: January 18, 2013
Last updated: July 16, 2014
Last verified: July 2014

January 18, 2013
July 16, 2014
February 2013
April 2015   (final data collection date for primary outcome measure)
  • Dose Escalation - Characterize Pharmacokinetics - Cmax [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Maximum Observed Plasma Concentration (Cmax)
  • Dose Escalation - Characterize Pharmacokinetics -Cmin [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Minimum Observed Concentration (Cmin)
  • Dose Escalation - Characterize Pharmacokinetics-Tmax [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Time to Reach Maximum Plasma Concentration (Tmax)
  • Dose Escalation - Characterize Pharmacokinetics - AUC12h [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Area under the curve until 12 hours after investigational product (IP) administration (AUC12h)
  • Dose Expansion - Characterize Pharmacokinetics - Cmax [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Maximum Observed Plasma Concentration (Cmax)
  • Dose Expansion - Characterize Pharmacokinetics - Cpredose [ Time Frame: predose before morning dose on Day1, weeks 2, 8 , 12, 16 and 20 ] [ Designated as safety issue: Yes ]
    Concentration prior to IP administration (Cpredose)
Same as current
Complete list of historical versions of study NCT01786512 on ClinicalTrials.gov Archive Site
  • Systolic Ejection Time(SET) (msec) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Systolic Ejection Time (SET)
  • Left Ventricular End-Systolic Diameter (LVESD) (cm) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Left Ventricular End-Systolic Diameter (LVESD)
  • Left Ventricular End-Diastolic Diameter (LVEDD) (cm) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Left Ventricular End-Diastolic Diameter (LVEDD)
  • Heart Rate (beats per minute) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in heart rate
  • Stroke Volume (ml) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Stroke Volume
  • Effect of omecamtiv mecarbil on NT-proBNP (pg/mL) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    To evaluate the effect of 12 weeks of oral dosing with omecamtiv mecarbil on Nterminal pro-B-type natriuretic peptide (NT-proBNP)
  • Dose Escalation - Safety and tolerability of oral omecamtiv mecarbil [ Time Frame: baseline to 35 days ] [ Designated as safety issue: Yes ]
    Subject incidence of adverse events from baseline to 35 days (end of study)
  • Dose Expansion - Safety and tolerability of oral omecamtiv mecarbil [ Time Frame: baseline to 24 weeks ] [ Designated as safety issue: Yes ]
    Subject incidence of adverse events from baseline to week 24 (end of study)
  • Systolic Ejection Time(SET) (msec) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Systolic Ejection Time (SET)
  • Left Ventricular End-Systolic Diameter (LVESD) (cm) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Left Ventricular End-Systolic Diameter (LVESD)
  • Left Ventricular End-Diastolic Diameter (LVEDD) (cm) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Left Ventricular End-Diastolic Diameter (LVEDD)
  • Heart Rate (beats per minute) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in heart rate
  • Stroke Volume (ml) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Stroke Volume
  • Effect of omecamtiv mecarbil on NT-proBNP (pg/mL) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    To evaluate the effect of 12 weeks of oral dosing with omecamtiv mecarbil on Nterminal pro-B-type natriuretic peptide (NT-proBNP)
  • Dose Escalation - Safety and tolerability of oral omecamtiv mecarbil [ Time Frame: baseline to 35 days ] [ Designated as safety issue: Yes ]
    Subject incidence of adverse events from baseline to 35 days (end of study)
  • Dose Expansion - Safety and tolerability of oral omecamtiv mecarbil [ Time Frame: baseline to 16 weeks ] [ Designated as safety issue: Yes ]
    Subject incidence of adverse events from baseline to week 16 (end of study)
Not Provided
Not Provided
 
COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure.
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Modified Release Oral Formulation
  • Left Ventricular Systolic Dysfunction
  • Chronic Heart Failure
  • History of Chronic Heart Failure
  • Left Ventricular Ejection Fraction
  • Pharmacokinetics
  • Echocardiogram
  • Drug: Omecamtiv mecarbil
    Oral omecamtiv mecarbil dose of 25-mg BID for 7 days
    Other Name: AMG 423
  • Drug: Omecamtiv mecarbil
    Oral omecamtiv mecardbil dose of 50-mg BID for 7 days.
    Other Name: AMG 423
  • Drug: Placebo
    Placebo
  • Drug: Omecamtiv Mecarbil
    Oral omecamtiv mecarbil dose of 25-mg BID for 20 weeks.
    Other Name: AMG 423
  • Drug: Omecamtiv Mecarbil
    Oral omecamtiv mecarbil dose of 25 mg BID for 8 weeks followed by 50-mg BID for 12 weeks
    Other Name: AMG 423
  • Experimental: Omecamtiv mecarbil
    Interventions:
    • Drug: Omecamtiv mecarbil
    • Drug: Omecamtiv mecarbil
    • Drug: Omecamtiv Mecarbil
    • Drug: Omecamtiv Mecarbil
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
570
June 2015
April 2015   (final data collection date for primary outcome measure)

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)

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
Both
18 Years to 85 Years
No
Contact: Amgen Call Center 866-572-6436
United States,   Australia,   Belgium,   Bulgaria,   Canada,   Czech Republic,   Germany,   Hungary,   Italy,   Lithuania,   Netherlands,   Poland,   United Kingdom
 
NCT01786512
20110151
Yes
Amgen
Amgen
Cytokinetics
Study Director: MD Amgen
Amgen
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP