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Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM

Phase 2
Completed
Conditions
Hypertrophic Cardiomyopathy (HCM)
Interventions
Drug: CK-3773274 (5 - 15 mg)
Drug: CK-3773274 (10 - 30 mg)
Drug: Placebo for CK-3773274
Registration Number
NCT04219826
Lead Sponsor
Cytokinetics
Brief Summary

This study is being performed to understand the effect of different doses of CK-3773274 on patients with hypertrophic cardiomyopathy (HCM).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
96
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CK-3773274 - Cohort 1 (Obstructive HCM)CK-3773274 (5 - 15 mg)Subjects will receive doses of 5 - 15 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks
CK-3773274 - Cohort 4 (non-obstructive HCM)CK-3773274 (5 - 15 mg)Subjects will receive doses of 5 - 15 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks
CK-3773274 - Cohort 2 (Obstructive HCM)CK-3773274 (10 - 30 mg)Subjects will receive doses 10 - 30 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks
Placebo - Cohort 1 (Obstructive HCM)Placebo for CK-3773274Subjects will receive placebo for up to 10 weeks
Placebo - Cohort 2 (Obstructive HCM)Placebo for CK-3773274Subjects will receive placebo for up to 10 weeks
CK-3773274 & disopyramide - Cohort 3 (Obstructive HCM)CK-3773274 (5 - 15 mg)Subjects will receive doses 5 - 15 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide
Primary Outcome Measures
NameTimeMethod
Incidence of adverse events observed during dosing of CK--3773274 in patients with HCM14 weeks

Patient incidence of reported adverse events (AEs)

Secondary Outcome Measures
NameTimeMethod
Incidence of serious adverse events observed during dosing of CK-3773274 in patients with HCM14 weeks

Patient incidence of reported serious adverse events (SAEs)

Incidence of left ventricular ejection fraction (LVEF) < 50% observed during dosing of CK-3773274 in patients with HCM14 weeks

Patient incidence of left ventricular ejection fraction (LVEF) \< 50%

Concentration-response relationship of CK-3773274 on the resting left ventricular outflow tract gradient (LVOT-G) on echocardiogram over 10 weeks of treatment in patients with oHCM (Cohorts 1, 2, 3 only)10 weeks

Slope of the relationship of the plasma concentration of CK-3773274 to the change from baseline in the resting LVOT-G

Concentration-response relationship of CK-3773274 on the post-Valsalva left ventricular outflow tract gradient (LVOT-G) on echocardiogram over 10 weeks of treatment in patients with oHCM (Cohorts 1, 2, 3 only)10 weeks

Slope of the relationship of the plasma concentration of CK-3773274 to the change from baseline in the post-Valsalva LVOT-G

Dose response relationship on LVOT-G of CK-3773274 in patients with oHCM at rest (Cohorts 1, 2, 3 only)10 weeks

Change from baseline in resting LVOT-G over time as a function of dose

Dose response relationship on LVOT-G of CK-3773274 in patients with oHCM post-Valsalva (Cohorts 1, 2, 3 only)10 weeks

Change from baseline in post-Valsalva LVOT-G over time as a function of dose

Concentration-response relationship of CK-3773274 on left ventricular ejection fraction (LVEF) over 10 weeks of treatment in patients with HCMDay 1 to End of Study (EOS) (Week 14)

Change from baseline in the resting LVEF

Trial Locations

Locations (22)

New York University Langone Health Medical Center

🇺🇸

New York, New York, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Intermountain Medical Center

🇺🇸

Murray, Utah, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

Erasmus University Medical Center (Erasmus MC)

🇳🇱

Rotterdam, Netherlands

Azienda Ospedaliero Universitaria Careggi

🇮🇹

Firenze, Italy

Complejo Hospitalario Universitario A Coruña

🇪🇸

A Coruña, Spain

Hospital Universitario Puerta de Hierro de Majadahonda

🇪🇸

Madrid, Spain

Cedar-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

UCSF Medical Center

🇺🇸

San Francisco, California, United States

Northwestern University

🇺🇸

Evanston, Illinois, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Michigan Medicine - University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Duke Cardiology at Southpoint

🇺🇸

Durham, North Carolina, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine)

🇺🇸

Philadelphia, Pennsylvania, United States

UMPC Heart and Vascular Institute

🇺🇸

Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

Carolinas Medical Center

🇺🇸

Charlotte, North Carolina, United States

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