Heart Failure
Conditions
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.
Interventions
DRUGCK-1827452
I.V. infusion for 0.5 hour at 54mg/hr followed by 1 hour at 21mg/hr
Sponsors
Cytokinetics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Effects of CK-1827452 on Ventricular Performance | 1 day | Measure the effect of CK-1824752 on ventricular performance |
| 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 Pressure-volume Relationships | 1 day | Measure the effect of CK-1824752 on pressure-volume relationships |
| Effects of CK-1827452 on Systolic Ejection Time | 1 day | Measure the effect of CK-1824752 on systolic ejection time |
| 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 |
Countries
Canada, United States
Participant flow
Recruitment details
The recruitment period was from September 2008 to July 2009.
Participants by arm
| Arm | Count |
|---|---|
| Mid Dose CK-1827452 (Cohort 1) 0.5 hour loading infusion followed by 1.0 hour maintenance infusion of CK-1827452 | 2 |
| High Dose CK-1827452 (Cohort 2) ≤ 1.0 hour loading infusion followed by 1.0 hour maintenance infusion of CK-1827452 | 0 |
| Total | 2 |
Baseline characteristics
| Characteristic | Mid Dose CK-1827452 (Cohort 1) | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Age, Continuous | 69 years STANDARD_DEVIATION 13 | 69 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 2 participants | 2 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 0 / 0 |
| serious Total, serious adverse events | 0 / 2 | 0 / 0 |
Outcome results
Primary
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.
Time frame: 1 day
Population: Study was terminated due to poor enrollment; 2 participants completed the study. Data quantity was insufficient to analyze or draw conclusions.
Secondary
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
Time frame: 1 day
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Secondary
Effects of CK-1827452 on Myocardial Oxygen Consumption
Measure the effect of CK-1824752 on myocardial oxygen consumption
Time frame: 1 day
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Secondary
Effects of CK-1827452 on Pressure-volume Relationships
Measure the effect of CK-1824752 on pressure-volume relationships
Time frame: 1 day
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Secondary
Effects of CK-1827452 on Systolic Ejection Time
Measure the effect of CK-1824752 on systolic ejection time
Time frame: 1 day
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Secondary
Effects of CK-1827452 on Ventricular Performance
Measure the effect of CK-1824752 on ventricular performance
Time frame: 1 day
Population: No data displayed because Outcome Measure has zero total participants analyzed.