Clinical trial NCT00624442: A Study of CK-1827452 Infusion in Stable Heart Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2008-02-27
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Change From Baseline of Systolic Ejection Time at Various CK-1827452 Plasma Concentrations
timeFrame: 4 days
measure: Change From Baseline of Fractional Shortening at Various CK-1827452 Plasma Concentrations
timeFrame: 4 days
Secondary outcomes:
measure: CK-1827452 Maximum Observed Plasma Concentration (Cmax)
timeFrame: 2 days
measure: CK-1827452 Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUClast)
timeFrame: 2 days
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego Medical Center
state: California
city: Newark
country: United States
facility: Christiana Care Health Services, Inc.
state: Delaware
city: Tbilisi
country: Georgia
facility: Diagnostic Services Clinic
city: Moscow
country: Russian Federation
facility: Russian Cardiological Research and Production Complex
city: St. Petersburg
country: Russian Federation
facility: Dzhanelidze Research Institute for Emergency Medical Care
city: St. Petersburg
country: Russian Federation
facility: Almazov Federal Heart, Blood and Endocrinology Center
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Medical University
city: Hull
country: United Kingdom
facility: Castle Hill Hospital, University of Hull
state: England
city: London
country: United Kingdom
facility: King's College Hospital
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: St. Mary's Hospital & Imperial College
state: England
city: Manchester
country: United Kingdom
facility: Manchester Heart Centre, Manchester Royal Infirmary
state: England
city: Manchester
country: United Kingdom
facility: ICON Development Solutions
state: England
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
state: England
city: Middlesex
country: United Kingdom
facility: Northwick Park Hospital
state: England
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
state: Scotland
city: Glasgow
country: United Kingdom
facility: BHF Cardiovascular Centre
state: Scotland
Study officials:
References:
citation: Vu T, Ma P, Xiao JJ, Wang YM, Malik FI, Chow AT. Population pharmacokinetic-pharmacodynamic modeling of omecamtiv mecarbil, a cardiac myosin activator, in healthy volunteers and patients with stable heart failure. J Clin Pharmacol. 2015 Nov;55(11):1236-47. doi: 10.1002/jcph.538. Epub 2015 Jul 14.
citation: Cleland JG, Teerlink JR, Senior R, Nifontov EM, Mc Murray JJ, Lang CC, Tsyrlin VA, Greenberg BH, Mayet J, Francis DP, Shaburishvili T, Monaghan M, Saltzberg M, Neyses L, Wasserman SM, Lee JH, Saikali KG, Clarke CP, Goldman JH, Wolff AA, Malik FI. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet. 2011 Aug 20;378(9792):676-83. doi: 10.1016/S0140-6736(11)61126-4.