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A Pharmacokinetic and Pharmacodynamic Study of Omecamtiv Mecarbil in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
Cytokinetics
ClinicalTrials.gov Identifier:
NCT01380223
First received: June 22, 2011
Last updated: NA
Last verified: June 2011
History: No changes posted
  Purpose

This study will assess the safety, tolerability, and pharmacodynamics of omecamtiv mecarbil infusion in healthy male volunteers.


Condition Intervention Phase
Heart Failure
 Drug: placebo
Drug: omecamtiv mecarbil
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A First-in-Man, Phase I, Double-Blind, Randomized, Four-Way Crossover, Placebo-Controlled, Dose-Escalation, Pharmacokinetic and Pharmacodynamic Study of CK-1827452 (Omecamtiv Mecarbil) in Healthy Volunteers

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Omecamtiv Mecarbil in Healthy Volunteers [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
    The highest infusion rate tolerated by at least eight subjects. A dose was intolerable if: 1) the pattern of intolerance clearly distinguished active drug from placebo, or 2) the number of subjects intolerant of the dose level in question was at least 3 more than the number of subjects intolerant of placebo.


Secondary Outcome Measures:
  • Change From Baseline of Systolic Ejection Time at Various Omecamtiv Mecarbil Infusion Rates [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Pooled analysis of the echocardiographic measure systolic ejection time. The systolic ejection time is the period during which the aortic valve is open and blood is flowing across the valve. Echocardiograms from cohorts 1,2,3,4 were binned into either placebo group or groups based on infusion rate of omecamtiv mecarbil.

  • Change From Baseline of Fractional Shortening at Various Omecamtiv Mecarbil Infusion Rates [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Pooled analysis of the echocardiographic measure fractional shortening. Fractional shortening is the percentage of change from baseline in the left ventricular cavity dimension with systole. Echocardiograms from cohorts 1,2,3,4 were binned into either placebo group or groups based on infusion rate of omecamtiv mecarbil.


Enrollment: 35
Study Start Date: August 2005
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose-escalation Cohort 1
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
 Drug: placebo
I.V. infusion of placebo for 8 hr
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.005 mg/kg/hr
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.015 mg/kg/hr
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.025 mg/kg/hr
Other Name: CK-1827452, AMG 423
Experimental: Dose-escalation Cohort 2
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
 Drug: placebo
I.V. infusion of placebo for 8 hr
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.025 mg/kg/hr
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.0625 mg/kg/hr
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.125 mg/kg/hr
Other Name: CK-1827452, AMG 423
Experimental: Dose-escalation Cohort 3
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
 Drug: placebo
I.V. infusion of placebo for 8 hr
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.125 mg/kg/hr
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.25 mg/kg/hr
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.5 mg/kg/hr
Other Name: CK-1827452, AMG 423
Experimental: Dose-escalation Cohort 4
4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.
 Drug: placebo
I.V. infusion of placebo for 8 hr
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.5 mg/kg/hr
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 1.0 mg/kg/hr
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.75 mg/kg/hr (dose reduced)
Other Name: CK-1827452, AMG 423
Drug: omecamtiv mecarbil
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.625 mg/kg/hr (dose reduced)
Other Name: CK-1827452, AMG 423

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Subject is male
  2. Subject is aged between 18 and 50 years inclusive.
  3. Subject has given signed informed consent.
  4. Subject's Body Mass Index (BMI) is between 18 and 30 kg/m2 inclusive.
  5. Subject weighs less than 100 kg.

  6. Subject is considered to be in good health in the opinion of the investigator, as determined by:

    1. A pre-study physical examination with no clinically significant abnormalities.
    2. Vital signs within normal ranges (supine after 3 minutes rest - heart rate: 40 to 80 bpm; systolic BP: 100 to 140 mmHg; diastolic BP: 50-90 mmHg; respiration rate: 8 to 18 breaths per minute; oxygen saturation: 96-100%)
    3. An ECG with no clinically significant abnormalities.
  7. Subject's pre-study clinical laboratory findings are within normal range or if outside of the normal range not deemed clinically significant in the opinion of the investigator.
  8. Cardiac troponin I is less than the upper limit of the laboratory reference range.
  9. A screening echocardiogram demonstrates normal cardiac function, an ejection fraction of between 40% and 70% with no significant valvular regurgitation (grade 1) and/or stenosis and images are deemed to be of good quality by the sonographer.

Exclusion Criteria:

  1. Subject has had a clinically significant illness in the four weeks before screening.
  2. Use of prescribed mediations in the 3 weeks prior to dosing or over-the-counter preparations (including vitamin supplements and herbal remedies) for 7 days prior to dosing, except paracetamol which will be allowed up to 48 hours prior to dosing.
  3. Subject has a significant history of drug/solvent abuse or a positive drugs of abuse test at screening.
  4. Subject with a history of alcohol abuse or currently drinks in excess of 28 units per week.
  5. Subject smokes more than 5 cigarettes (or equivalent) per day.
  6. Subject is not willing to refrain from caffeine/xanthine containing products from 48 hours prior to the screening medical and admission on Day -1 until the post study medical.
  7. Subject is in the opinion of the investigator not suitable to participate in the study.
  8. Subject who has participated in any clinical study with an investigational drug/device within three months prior to the first day of dosing.
  9. Subject who has a positive result of HIV screen, Hepatitis B screen or Hepatitis C screen.
  10. Subject has had a serious adverse reaction or significant hypersensitivity to any drug.
  11. Subject has donated 500 ml or more of blood within the month prior to screening.
  12. Subject has a history of cardiovascular disease or family history of premature cardiovascular disease or death.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01380223

Locations
United Kingdom
ICON Development Solutions
Manchester, England, United Kingdom, United Kingdom
Sponsors and Collaborators
Cytokinetics
  More Information

No publications provided by Cytokinetics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Andrew Wolff, M.D., F.A.C.C., Chief Medical Officer, Cytokinetics, Inc.
ClinicalTrials.gov Identifier: NCT01380223     History of Changes
Other Study ID Numbers: CY 1111, 2005-001886-32
Study First Received: June 22, 2011
Last Updated: June 22, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on May 22, 2013