Pharmacokinetic and Pharmacodynamic study to evaluate the effect of CK-3773274 in patients with obstructive hypertrophic cardiomyopathy (oHCM)
- Conditions
- obstructive hypertrophic cardiomyopathy (oHCM)MedDRA version: 20.0Level: PTClassification code 10020871Term: Hypertrophic cardiomyopathySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2019-002785-12-ES
- Lead Sponsor
- Cytokinetics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 60
Able to comprehend and willing to sign an ICF and willing to comply with all study procedures and restrictions for the duration specified in the Schedule of Activities (SoA).
Males and females between 18 and 70 years of age at Screening.
Body weight is =45 kg at Screening.
Diagnosed with oHCM per the following criteria:
• Has LV hypertrophy and non-dilated LV chamber in the absence of other cardiac disease.
• Has minimal wall thickness =15 mm at time of initial diagnosis (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.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16
Aortic stenosis or fixed subaortic obstruction.
Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM (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.
Has been treated with disopyramide or antiarrhythmic drugs that have negative inotropic activity within 4 weeks prior to screening.
Documented atrial fibrillation during the Screening period.
Paroxysmal atrial fibrillation or flutter requiring treatment (eg, anti-coagulation or antiarrhythmic therapy including disopyramide) documented within the 6 months prior to Screening.
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the safety and tolerability of CK3773274 in patients with symptomatic oHCM;Secondary Objective: To describe the concentration-response relationship of CK3773274 on the resting and post-Valsalva LVOT-G on echocardiogram over 10 weeks of treatment.<br>To describe the dose response relationship of CK3773274 in patients with symptomatic oHCM.<br>To evaluate the plasma concentrations of CK3773274 in patients with oHCM.;Primary end point(s): • Patient incidence of reported AEs <br>• Patient incidence of reported SAEs <br>• Patient incidence of LVEF < 50%;Timepoint(s) of evaluation of this end point: Week 14
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • The slope of the relationship of the plasma concentration of CK3773274 to the change from baseline in the resting LVOT-G<br>• The slope of the relationship of the plasma concentration of CK3773274 to the change from baseline in the post-Valsalva LVOT-G<br>• The change from baseline in resting and post-Valsalva LVOT-G over time as a function of dose<br>• The change from baseline in resting and post-Valsalva LVOT-G to Week 10<br>• Observed maximum plasma concentration (Cmax) and trough plasma concentration (Ctrough) for CK-3773274;Timepoint(s) of evaluation of this end point: Week 10