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

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

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.

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Drug: CK-1827452; Drug: CK-1827452

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Medical Institutions
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • UUHSC / Division of Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cytokinetics

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: April 21, 2008
• First Submitted That Met QC Criteria: September 4, 2008
• First Posted (Estimate): September 8, 2008

Study Record Updates

• Last Update Posted (Actual): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CY 1124

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No