Phase II Study of the Effect of CK-1827452 Injection on Myocardial Efficiency

Phase 2

Terminated

Brief Summary: The purpose for this study (CY 1124) is to evaluate the effects of CK-1827452, a cardiac myosin activator, on myocardial systolic performance, myocardial oxygen consumption, and myocardial efficiency in patients with heart failure and to confirm that the unique preclinical pharmacological profile of CK- 1827452 is substantially the same in patients with heart failure.

Recruitment & Eligibility

Inclusion Criteria

Clinical indication for left and right heart catheterization
Willing and able to provide informed consent
Male or female 18 years of age or greater
Symptomatic heart failure (≥ NYHA Class II)
Ejection fraction ≤ 35%
Patient is in sinus rhythm
Patient is considered to be in suitable health in the opinion of the investigator, as determined by:

o 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
For female patients only: Post-menopausal or sterilized, or if she is of childbearing potential, she is not breastfeeding, her pregnancy test is negative, she has no intention to become pregnant for up to 90 days following the study, and she is using contraceptive drugs or devices

Exclusion Criteria

Acute myocarditis
Hypertrophic, restrictive, or constrictive cardiomyopathy
Congenital heart disease
Known left ventricular thrombus
Significant stenotic valvular disease (severe aortic stenosis, mitral stenosis)
Poorly controlled hypertension (SBP > 180 mmHg)
Pacemaker dependent ventricular rhythm
Detectable troponin or CK-MB > ULN at any timepoint within 14 days of enrollment
Acute coronary syndrome or revascularization procedure within 30 days of enrollment
≥ 50% stenosis of the left main coronary artery
Plan for immediate revascularization procedure (PCI or CABG)
GFR ≤ 35 ml/min/1.73 m2 by Modification of Diet in Renal Disease (MDRD) Equation or need for renal replacement therapy
Known hepatic impairment (total bilirubin > 3 mg/dL, or ALT and AST > 2 times the upper limit of normal)
Has received an investigational drug or device within 30 days before enrollment
Has had any prior treatment with CK-1827452

Arm && Interventions

Group	Intervention	Description
Cohort 1	CK-1827452	0.5 hour loading dose followed by 1.0 hour maintenance dose of CK-1827452
Cohort 2	CK-1827452	≤ 1.0 hour loading dose followed by 1.0 hour maintenance dose of CK-1827452

Primary Outcome Measures

Name	Time	Method
Effect of CK-1827452 on Myocardial Efficiency, Defined as the Ratio of Ventricular Performance to Myocardial Oxygen Consumption.	1 day	Measure the effect CK-1827452 on hemodynamics and energetic measures of ventricular performance, myocardial oxygen consumption, and myocardial efficiency (the ratio of ventricular performance to myocardial oxygen consumption), in patients with clinical heart failure.

Secondary Outcome Measures

Name	Time	Method
Effects of CK-1827452 on Ventricular Performance	1 day	Measure the effect of CK-1824752 on ventricular performance
Effects of CK-1827452 on Pressure-volume Relationships	1 day	Measure the effect of CK-1824752 on pressure-volume relationships
Effects of CK-1827452 on Myocardial Oxygen Consumption	1 day	Measure the effect of CK-1824752 on myocardial oxygen consumption
Effects of CK-1827452 on Invasively Measured Hemodynamics, Including Filling Pressure and Cardiac Output	1 day	Measure the effect of CK-1824752 on invasively measured hemodynamics, including filling pressure and cardiac output
Effects of CK-1827452 on Systolic Ejection Time	1 day	Measure the effect of CK-1824752 on systolic ejection time

Locations (3): Johns Hopkins Medical Institutions
🇺🇸
Baltimore, Maryland, United States
Mount Sinai Hospital
🇨🇦
Toronto, Ontario, Canada
UUHSC / Division of Cardiology
🇺🇸
Salt Lake City, Utah, United States