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A Study of CK-1827452 Infusion in Stable Heart Failure
This study is currently recruiting participants.
Verified by Cytokinetics, January 2009
Sponsored by: Cytokinetics
Information provided by: Cytokinetics
ClinicalTrials.gov Identifier: NCT00624442
  Purpose

This study will assess the safety, tolerability, and pharmacodynamics of CK-1827452 infusion in patients with stable heart failure.


Condition Intervention Phase
Heart Failure
Drug: CK-1827452
Drug: Placebo
Phase II

MedlinePlus related topics: Heart Failure
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study
Official Title: A Phase II, Multi Center, Double-Blind, Randomized, Placebo Controlled, Dose-Escalation, Pharmacokinetic and Pharmacodynamic Study of CK-1827452 in Patients With Stable Heart Failure

Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • Evaluate the safety and tolerability of CK-1827452 Injection administered by intravenous infusion in patients with stable heart failure as measured by the frequency and severity of adverse events. [ Time Frame: 5 weeks ] [ Designated as safety issue: Yes ]
  • Assess the effect of CK-1827452 Injection administered by intravenous infusion on pharmacodynamic response (ejection fraction, fractional shortening and systolic ejection time) in patients with stable heart failure. [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Establish a relationship between plasma concentration and pharmacodynamic effect for CK 1827452 Injection. [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
  • Determine the pharmacokinetics of CK-1827452 Injection in stable heart failure patients. [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: April 2007
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Cohort 1: Experimental
2 hour infusion of one of three dose levels of CK-1827452 or placebo.
Drug: CK-1827452
I.V. infusion for 1 hour at 0.125mg/kg/hr followed by 1 hour at 0.0625mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.25mg/kg/hr followed by 1 hour at 0.125mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.5mg/kg/hr followed by 1 hour at 0.25mg/kg/hr
Drug: Placebo
I.V. infusion for 2 hours
Cohort 2: Experimental
2 hour infusion of one of three dose levels of CK-1827452 or placebo.
Drug: CK-1827452
I.V. infusion for 1 hour at 0.5mg/kg/hr followed by 1 hour at 0.25mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.75mg/kg/hr followed by 1 hour at 0.375mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 1.0mg/kg/hr followed by 1 hour at 0.5mg/kg/hr
Drug: Placebo
I.V. infusion for 2 hours
Cohort 3: Experimental
24 hour infusion of one of three dose levels of CK-1827452 or placebo.
Drug: CK-1827452
I.V. infusion for 1 hour at 0.25mg/kg/hr followed by 1 hour at 0.125mg/kg/hr followed by 22 hours at 0.025mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.5mg/kg/hr followed by 1 hour at 0.25mg/kg/hr followed by 22 hours at 0.05mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 1.0mg/kg/hr followed by 1 hour at 0.5mg/kg/hr followed by 22 hours at 0.1mg/kg/hr
Drug: Placebo
I.V. infusion for 24 hours
Cohort 4: Experimental
24 hour infusion of one of three dose levels of CK-1827452 or placebo.
Drug: CK-1827452
I.V. infusion for 1 hour at 0.25mg/kg/hr followed by 1 hour at 0.125mg/kg/hr followed by 22 hours at 0.025mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.5mg/kg/hr followed by 1 hour at 0.25mg/kg/hr followed by 22 hours at 0.05mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 1.0mg/kg/hr followed by 1 hour at 0.5mg/kg/hr followed by 22 hours at 0.1mg/kg/hr
Drug: Placebo
I.V. infusion for 24 hours
Cohort 5: Experimental
72 hour infusion with one dose level of CK-1827452 or placebo.
Drug: CK-1827452
I.V. infusion for 1 hour at 1.0mg/kg/hr followed 1 hour at 0.5mg/kg/hr followed by 70 hours at 0.1mg/kg/hr
Drug: Placebo
I.V. infusion for 72 hours

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Patient is male, or female of non-childbearing potential (two years post-menopausal or surgically sterilized)
  2. Female patients must have a negative urine pregnancy test prior to entry into the study
  3. Patient is 18 years old or greater
  4. Patient has given signed informed consent
  5. Patient is considered to be in suitable health in the opinion of the investigator, as determined by:

    • A pre-study physical examination with no clinical abnormalities which in the opinion of the investigator would preclude participation in the study other than physical symptoms or signs consistent with stable heart failure
    • An electrocardiogram (ECG) with no abnormalities in the opinion of the investigator that would impair assessment of stopping criteria
  6. Patient has pre-study clinical laboratory findings that are within normal range, or if outside of the normal range, should not preclude participation in the study in the opinion of the investigator (see Exclusion Criteria, below, for exceptions)
  7. Patient has a documented diagnosis of heart failure with an ejection fraction of less than 40%
  8. Patient has been on a stable dose of a beta blocker and an ACE inhibitor (or an ARB) for at least 4 weeks. If prescribed, diuretics must have been administered according to a consistent regimen for at least 4 weeks
  9. Patient is currently in sinus rhythm
  10. Patient has interpretable echocardiographic images on a screening echocardiogram

Exclusion Criteria

  1. Patient has been hospitalized for heart failure, myocardial infarction, coronary revascularization, or another cardiac indication within the last 6 weeks
  2. Patient has a current history of alcohol use which in the opinion of the investigator would preclude participation in the study
  3. Patient has a current history of drug abuse
  4. Patient has donated blood or blood products within 30 days prior to screening
  5. Patient has CCS Class III or IV angina
  6. Patient has significant obstructive valvular disease or significant congenital heart disease
  7. Patient has had a valve replacement
  8. Patient is pacemaker dependent
  9. Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone
  10. Patient is currently taking, or has taken in the last 7 days, a CYP3A4 inhibitor or inducer medication listed in Appendix C
  11. Patient has a history of hypertrophic obstructive cardiomyopathy
  12. Patient weighs > 120 kg
  13. Patient has a supine resting systolic blood pressure < 95 mmHg after 3 minutes rest
  14. Patient has a supine resting heart rate ≥ 100 beats per minute after 3 minutes rest
  15. Patient has an Modification of Diet in Renal Disease (MDRD) estimate of GFR ≤ 35 ml/min/1.73 m2 (see Appendix D)
  16. Patient has a potassium < 3.5 mEq/L or > 5.5 mEq/L
  17. Patient has a sodium ≤ 133 mEq/L
  18. Patient has a urea > 15 mmole/L
  19. Patient has a troponin I or T at screening that is detectable at the investigative site's clinical laboratory
  20. Patient has a hemoglobin < 11 gm/dL in males or < 10 gm/dL in females
  21. Patient has an ALT, AST, ALKP or TBILI > 3 times the upper limit of normal
  22. Patient is, in the opinion of the investigator, not suitable to participate in the study
  23. Patient has participated in any clinical study with an investigational drug within three months prior to the first day of dosing with the exception of coronary stent studies Patient has ever received CK-1827452
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00624442

Contacts
Contact: Cyril Clarke, MB BS, MFPM clarkec@iconuk.com

Locations
United States, California
University of California, San Diego Medical Center Recruiting
San Diego, California, United States, 92103
United States, Delaware
Christiana Care Health Services, Inc. Recruiting
Newark, Delaware, United States, 19713
Georgia
Diagnostic Services Clinic Recruiting
Tbilisi, Georgia
Russian Federation, Russia
St. Petersburg State Medical University Recruiting
St. Petersburg, Russia, Russian Federation, 197089
Almazov Federal Heart, Blood and Endocrinology Center Recruiting
St. Petersburg, Russia, Russian Federation, 194156
Russian Cardiological Research and Production Complex Recruiting
Moscow, Russia, Russian Federation, 121552
United Kingdom, England
Manchester Heart Centre, Manchester Royal Infirmary Recruiting
Manchester, England, United Kingdom, M13 9WL
Wythenshawe Hospital Recruiting
Manchester, England, United Kingdom, M23 9LT
Castle Hill Hospital, University of Hull Recruiting
Hull, England, United Kingdom, HU16 5JQ
King's College Hospital Recruiting
London, England, United Kingdom, SE5 9RS
Northwick Park Hospital Recruiting
Middlesex, England, United Kingdom, HA1 3UJ
ICON Development Solutions Active, not recruiting
Manchester, England, United Kingdom, M15 6SH
St. Mary's Hospital & Imperial College Recruiting
London, England, United Kingdom, W2 1LA
St. George's Hospital Recruiting
London, England, United Kingdom, SW17 ORE
United Kingdom, Scotland
BHF Cardiovascular Centre Recruiting
Glasgow, Scotland, United Kingdom, G12 8TA
Ninewells Hospital and Medical School Recruiting
Dundee, Scotland, United Kingdom, DD1 9SY
Sponsors and Collaborators
Cytokinetics
  More Information

Responsible Party: Cytokinetics, Inc. ( Andrew Wolff, M.D., F.A.C.C., Chief Medical Officer )
Study ID Numbers: CY 1121
Study First Received: December 21, 2007
Last Updated: January 4, 2009
ClinicalTrials.gov Identifier: NCT00624442  
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency;   Russia: Ministry of Health and Social Development of the Russian Federation;   United States: Food and Drug Administration

Study placed in the following topic categories:
Heart Failure
Heart Diseases

Additional relevant MeSH terms:
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009