A Study of CK-1827452 Infusion in Stable Heart Failure

This study has been completed.
Sponsor:
Information provided by:
Cytokinetics
ClinicalTrials.gov Identifier:
NCT00624442
First received: December 21, 2007
Last updated: June 28, 2011
Last verified: June 2011
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Multi Center, Double-Blind, Randomized, Placebo Controlled, Dose-Escalation, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of CK-1827452 in Patients With Stable Heart Failure

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • Change From Baseline of Systolic Ejection Time at Various CK-1827452 Plasma Concentrations [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    Pooled analysis of the echocardiographic measure systolic ejection time from echocardiograms taken at all timepoints. 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 and 5 (564 echocardiograms) were binned into either placebo group or 1 of 6 groups based on plasma concentration of CK-1827452.

  • Change From Baseline of Fractional Shortening at Various CK-1827452 Plasma Concentrations [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    Pooled analysis of the echocardiographic measure fractional shortening from echocardiograms taken at all timepoints. Fractional shortening is the percentage of change from baseline in the left ventricular cavity dimension with systole. Echocardiograms from cohorts 1,2,3,4 and 5 (564 echocardiograms) were binned into either placebo group or 1 of 6 groups based on plasma concentration of CK-1827452.


Secondary Outcome Measures:
  • Pharmacokinetics of CK-1827452 Injection in Stable Heart Failure Patients [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: April 2007
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
4 treatment periods with a 2 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart.
Drug: CK-1827452
I.V. infusion for 1 hour at 0.125 mg/kg/hr followed by 1 hour at 0.0625 mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.25 mg/kg/hr followed by 1 hour at 0.125 mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.5 mg/kg/hr followed by 1 hour at 0.25 mg/kg/hr
Drug: Placebo
I.V. infusion for 2 hours
Experimental: Cohort 2
4 treatment periods with a 2 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart.
Drug: CK-1827452
I.V. infusion for 1 hour at 0.5 mg/kg/hr followed by 1 hour at 0.25 mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.75 mg/kg/hr followed by 1 hour at 0.375 mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 1.0 mg/kg/hr followed by 1 hour at 0.5 mg/kg/hr
Drug: Placebo
I.V. infusion for 2 hours
Experimental: Cohort 3
4 treatment periods with a 24 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart.
Drug: Placebo
I.V. infusion for 24 hours
Drug: CK-1827452
I.V. infusion for 1 hour at 0.25 mg/kg/hr followed by 23 hours at 0.025 mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.5 mg/kg/hr followed by 23 hours at 0.05 mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 1.0 mg/kg/hr followed by 23 hours at 0.1 mg/kg/hr
Experimental: Cohort 4
4 treatment periods with a 24 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart.
Drug: CK-1827452
I.V. infusion for 1 hour at 0.25 mg/kg/hr followed by 1 hour at 0.125 mg/kg/hr followed by 22 hours at 0.025 mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 0.5 mg/kg/hr followed by 1 hour at 0.25 mg/kg/hr followed by 22 hours at 0.05 mg/kg/hr
Drug: CK-1827452
I.V. infusion for 1 hour at 1.0 mg/kg/hr followed by 1 hour at 0.5 mg/kg/hr followed by 22 hours at 0.1 mg/kg/hr
Drug: Placebo
I.V. infusion for 24 hours
Experimental: Cohort 5
2 treatment periods with a 72 hour infusion. The 2 treatment periods are randomly assigned and consist of 1 dose level of CK-1827452 (with dose de-escalation possible depending on tolerability) and 1 placebo treatment. Treatment period 2 occurs at least 7 days after the conclusion of period 1.
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
Drug: CK-1827452
I.V. infusion for 1 hour at 0.75 mg/kg/hr followed 1 hour at 0.5mg/kg/hr followed by 70 hours at 0.1 mg/kg/hr

  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 (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin II receptor blocker) 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 Canadian Cardiovascular Society (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
  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 Glomerular Filtration Rate (GFR) ≤ 35 ml/min/1.73 m2
  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 alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALKP) or total bilirubin (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00624442

Locations
United States, California
University of California, San Diego Medical Center
San Diego, California, United States, 92103
United States, Delaware
Christiana Care Health Services, Inc.
Newark, Delaware, United States, 19713
Georgia
Diagnostic Services Clinic
Tbilisi, Georgia
Russian Federation
Russian Cardiological Research and Production Complex
Moscow, Russia, Russian Federation, 121552
Almazov Federal Heart, Blood and Endocrinology Center
St. Petersburg, Russia, Russian Federation, 194156
St. Petersburg State Medical University
St. Petersburg, Russia, Russian Federation, 197089
Dzhanelidze Research Institute for Emergency Medical Care
St. Petersburg, Russia, Russian Federation, 192242
United Kingdom
Castle Hill Hospital, University of Hull
Hull, England, United Kingdom, HU16 5JQ
St. George's Hospital
London, England, United Kingdom, SW17 ORE
King's College Hospital
London, England, United Kingdom, SE5 9RS
St. Mary's Hospital & Imperial College
London, England, United Kingdom, W2 1LA
ICON Development Solutions
Manchester, England, United Kingdom, M15 6SH
Manchester Heart Centre, Manchester Royal Infirmary
Manchester, England, United Kingdom, M13 9WL
Wythenshawe Hospital
Manchester, England, United Kingdom, M23 9LT
Northwick Park Hospital
Middlesex, England, United Kingdom, HA1 3UJ
Ninewells Hospital and Medical School
Dundee, Scotland, United Kingdom, DD1 9SY
BHF Cardiovascular Centre
Glasgow, Scotland, United Kingdom, G12 8TA
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: NCT00624442     History of Changes
Other Study ID Numbers: CY 1121
Study First Received: December 21, 2007
Results First Received: February 28, 2010
Last Updated: June 28, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Russia: Ministry of Health of the Russian Federation
United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 18, 2014