A Study of CK-1827452 Infusion in Stable Heart Failure

Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00624442
• Other study ID #: CY 1121
• Status: Completed
• Phase: Phase 2
• Start date: April 2007
• Est. completion date: February 2009

Study information

• Verified date: April 2021
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• CK-1827452
IV infusion for 1 hour at 0.125 mg/kg/h followed by 1 hour at 0.0625 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 0.75 mg/kg/h followed by 1 hour at 0.375 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h followed by 22 hours at 0.025 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h followed by 22 hours at 0.05 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h followed by 22 hours at 0.1 mg/kg/h
• Placebo
IV infusion for 2 hours
• Placebo
IV infusion for 24 hours
• CK-1827452
IV infusion for 1 hour at 1.0 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h
• Placebo
IV infusion for 72 hours
• CK-1827452
IV infusion for 1 hour at 0.75 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 0.25 mg/kg/h followed by 23 hours at 0.025 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 0.5 mg/kg/h followed by 23 hours at 0.05 mg/kg/h
• CK-1827452
IV infusion for 1 hour at 1.0 mg/kg/h followed by 23 hours at 0.1 mg/kg/h

Locations

Country	Name	City	State
Georgia	Diagnostic Services Clinic	Tbilisi
Russian Federation	Russian Cardiological Research and Production Complex	Moscow
Russian Federation	Almazov Federal Heart, Blood and Endocrinology Center	St. Petersburg
Russian Federation	Dzhanelidze Research Institute for Emergency Medical Care	St. Petersburg
Russian Federation	St. Petersburg State Medical University	St. Petersburg
United Kingdom	Ninewells Hospital and Medical School	Dundee	Scotland
United Kingdom	BHF Cardiovascular Centre	Glasgow	Scotland
United Kingdom	Castle Hill Hospital, University of Hull	Hull	England
United Kingdom	King's College Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	St. Mary's Hospital & Imperial College	London	England
United Kingdom	ICON Development Solutions	Manchester	England
United Kingdom	Manchester Heart Centre, Manchester Royal Infirmary	Manchester	England
United Kingdom	Wythenshawe Hospital	Manchester	England
United Kingdom	Northwick Park Hospital	Middlesex	England
United States	Christiana Care Health Services, Inc.	Newark	Delaware
United States	University of California, San Diego Medical Center	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Countries where clinical trial is conducted

United States,  Georgia,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline of Systolic Ejection Time at Various CK-1827452 Plasma Concentrations	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.	4 days
Primary	Change From Baseline of Fractional Shortening at Various CK-1827452 Plasma Concentrations	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.	4 days
Secondary	CK-1827452 Maximum Observed Plasma Concentration (Cmax)	Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion	2 days
Secondary	CK-1827452 Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUClast)	Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion	2 days