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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Open-Label Study to Investigate the Effects of CK-1827452 Injection on Ventricular Performance, Myocardial Oxygen Consumption, and Myocardial Efficiency in Patients With Heart Failure and Left Ventricular Systolic Dysfunction

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: CK-1827452
* Drug: CK-1827452


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>0.5 hour loading dose followed by 1.0 hour maintenance dose of CK-1827452 | Drug: CK-1827452<br>* I.V. infusion for 0.5 hour at 54mg/hr followed by 1 hour at 21mg/hr<br>|
| Experimental: Cohort 2<br>≤ 1.0 hour loading dose followed by 1.0 hour maintenance dose of CK-1827452 | Drug: CK-1827452<br>* I.V. infusion for ≤ 1 hour at 72mg/hr followed by 1 hour at 36mg/hr<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of CK-1827452 on Myocardial Efficiency, Defined as the Ratio of Ventricular Performance to Myocardial Oxygen Consumption. | 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. | 1 day | 

Secondary Outcome Measures

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