A multi-center, randomized, double-blind, placebo-controlled, dose-finding study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-3773274 in adults with symptomatic hypertrophic cardiomyopathy
- Conditions
- Hypertrophic Cardiomyopathythickened heart muscle10028593
- Registration Number
- NL-OMON52672
- Lead Sponsor
- Cytokinetics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 6
Males and females between 18 and 85 years of age at Screening.
Body weight is >=45 kg at Screening.
Diagnosed with HCM per the following criteria:
• Has LV hypertrophy with non-dilated LV chamber in the absence of other
cardiac disease.
• Has minimal wall thickness >=15 mm (minimal wall thickness >=13 mm is
acceptable with a positive family history of HCM or with a known
disease-causing gene mutation).
Adequate acoustic windows for echocardiography.
For Cohorts 1,2 and 3 has LVOT-G during screening as follows:
• Resting gradient >=50 mmHg
OR
• Resting gradient >=30 mmHg and <50 mmHg with post-Valsalva LVOT G >=50 mmHg
LVEF >=60% at screening.
New York Heart Association (NYHA) Class II or III at Screening.
Patients on beta-blockers, verapamil, diltiazem, or ranolazine should have been
on stable doses for >4 weeks prior to Randomization and anticipate remaining on
the same medication regimen during the study.
For Cohort 3: Patients must be taking disopyramide. Patients should have been
on stable disopyramide doses for >4 weeks prior to screening and anticipate
remaining on the same medication regimen during the study.
For Cohort 4 has resting and post-Valsalva LVOT-G <30 mmHg at the time of
screening.
For Cohort 4 has elevated NT-proBNP >300 pg/mL at the time of screening.
A full listing can be found in Protocol section 5.
- Aortic stenosis or fixed subaortic obstruction.
- Known infiltrative or storage disorder causing cardiac hypertrophy that
mimics HCM (eg, Noonan syndrome, Fabry disease, amyloidosis).
- History of LV systolic dysfunction (LVEF <45%) at any time during their
clinical course.
- Documented history of current obstructive coronary artery disease (>70%
stenosis in one or more epicardial coronary arteries) or documented history of
myocardial infarction.
- Has been treated with septal reduction therapy (surgical myectomy or
percutaneous alcohol septal ablation) or has plans for either treatment during
the study period (Cohorts 1, 2, and 3 only). Patients having undergone septal
reduction therapy > 12 months prior to screening who remain symptomatic from
nHCM, and who meet all other criteria for inclusion, may be enrolled in Cohort
4.
- For Cohorts 1, 2 and 4: Has been treated with disopyramide or antiarrhythmic
drugs that have negative inotropic activity within 4 weeks prior to screening.
For Cohort 3, use of disopyramide is required.
- Paroxysmal atrial fibrillation or flutter documented during the Screening
period.
- Paroxysmal or permanent atrial fibrillation requiring rhythm restoring
treatment (eg, direct-current cardioversion, ablation procedure, or
antiarrhythmic therapy) <=6 months prior to screening. (This exclusion does not
apply if atrial fibrillation has been treated with anticoagulation and
adequately rate-controlled for >6 months.)
- History of syncope or sustained ventricular tachyarrhythmia with exercise
within 6 months prior to Screening.
- Has received prior treatment with CK3773274 or is currently receiving
mavacamten.
- For Cohort 4: has any documented history of LVOT-G >= 30 mmHg at rest, with
Valsalva, or with exercise (for subjects who have had prior septal reduction
therapy, this exclusion criteria only applies to gradients detected following
septal reduction therapy).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Patient incidence of reported adverse events (AEs)<br /><br>- Patient incidence of reported serious adverse events (SAEs)<br /><br>- Patient incidence of left ventricular ejection fraction (LVEF) <50%</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Slope of the relationship of the plasma concentration of CK-3773274 to the<br /><br>change from baseline in the resting LVOT-G<br /><br>- Slope of the relationship of the plasma concentration of CK-3773274 to the<br /><br>change from baseline in the post-Valsalva LVOT-G<br /><br>- Change from baseline in resting and post-Valsalva LVOT-G over time as a<br /><br>function of dose<br /><br>- Change from baseline in resting and post-Valsalva LVOT-G to Week 10<br /><br>- Slope of the relationship of the plasma concentration of CK-3773274 to the<br /><br>change from baseline in the resting LVEF<br /><br>- Observed maximum plasma concentration (Cmax) and trough plasma concentration<br /><br>(Ctrough) for CK-3773274 during dosing </p><br>