Hypertrophic Cardiomyopathy
Conditions
Interventions
In Cohorts 1 and 2, subjects will receive CK-3773274 or placebo. In Cohorts 3
and 4, subjects will receive CK-3773274. CK-3773274 is administered as an oral
tablet at doses of 5-30 mg per day.
Sponsors
Cytokinetics, Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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 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 300 pg/mL at the time of screening. A full listing can be found in Protocol section 5.
Exclusion criteria
Exclusion criteria: - 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 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.) - 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Patient incidence of reported adverse events (AEs) - Patient incidence of reported serious adverse events (SAEs) - Patient incidence of left ventricular ejection fraction (LVEF) | — |
Secondary
| Measure | Time frame |
|---|---|
| - Slope of the relationship of the plasma concentration of CK-3773274 to the change from baseline in the resting LVOT-G - Slope of the relationship of the plasma concentration of CK-3773274 to the change from baseline in the post-Valsalva LVOT-G - Change from baseline in resting and post-Valsalva LVOT-G over time as a function of dose - Change from baseline in resting and post-Valsalva LVOT-G to Week 10 - Slope of the relationship of the plasma concentration of CK-3773274 to the change from baseline in the resting LVEF - Observed maximum plasma concentration (Cmax) and trough plasma concentration (Ctrough) for CK-3773274 during dosing | — |
Countries
Netherlands
Outcome results
None listed