Purpose

This is a Phase 2, multicenter, double-blind, sponsor blinded, placebo-controlled, repeat-dose clinical study of CRD-4730 to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CRD-4730 to participants with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Participants with CPVT will complete a 3-period, randomized 3-sequence study. Each participant will be randomized to one of the 3 sequences in which they will receive 2 different doses of CRD-4730 and 1 dose of matching placebo.

Condition

Eligibility

Eligible Ages
Between 18 Years and 99 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

Each participant must meet all the following criteria to be enrolled in this study: 1. The participant is male or female, ≥18 years of age and of legal adult age in accordance with local requirements. 2. The participant has a confirmed CPVT diagnosis, based on genetic screening for a pathogenic ryanodine receptor (RYR2) mutation and a clinical phenotype consistent with CPVT at Screening. Previous CPVT genetic testing documented in medical history is acceptable if confirmed by the Investigator and documented in the study source records. 3. The participant can perform an EST during which frequent premature ventricular contractions (PVCs; ≥10 per minute), ventricular bigeminy, or higher-grade VA (equivalent to a VA score ≥2) are identified by the Investigator. 4. The participant has been on a stable dose of at least 1 antiarrhythmic medication (including beta blockers but not amiodarone) for 4 weeks prior to Screening, unless the participant has been unable to tolerate antiarrhythmic therapy previously. 5. Adheres to all contraceptive criteria.

Exclusion Criteria

Participants meeting any of the following criteria will be excluded from the study: 1. The participant has clinically significant structural heart disease, diagnosis of heart failure, or clinically significant coronary artery disease. 2. The participant has a clinically significant abnormal ECG not explained by the diagnosis of CPVT at Screening or clinically significant abnormal intervals, such as prolonged QT. 3. The participant has a history of a myocardial infarction, cerebrovascular accident, or transient ischemic attack within 3 months of Screening. 4. The participant undergoes implantable cardioverter-defibrillator (ICD) implantation or has sympathetic nerve denervation within 3 months of Screening. 5. The participant has an anticipated change in exercise regimen or new exercise program during the course of the study. 6. The participant has a history of malignancy within the past 5 years at Screening, with the exception of successfully treated basal cell carcinoma or nonmetastatic squamous cell carcinoma of the skin or cervical carcinoma in situ. Prior exposure to chest radiation for any malignancy is exclusionary. 7. The participant has abnormal blood pressure, defined as supine symptomatic hypotension, systolic blood pressure >150 mm Hg or diastolic blood pressure >90 mm Hg, or symptomatic bradycardia or a heart rate >100 bpm at Screening and/or on Day 1. Blood pressure and pulse should be measured after the participant has been in the seated position after 5 minutes of rest. 8. The participant has hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × (upper limit of normal [ULN]) and/or total bilirubin >1.5 × ULN at Screening (unless secondary to confirmed Gilbert syndrome). 9. The participant has acute or chronic hepatitis B (HBV; defined as hepatitis B surface antigen [HBsAg] reactive), acute or chronic hepatitis C virus (HCV; defined as detection of HCV antibody and RNA [qualitative]), or human immunodeficiency virus (HIV) infection. 10. The female participant is pregnant, lactating/breastfeeding, or has plans to become pregnant during the study or within 3 months following the last study drug administration. 11. The participant has taken any antiarrhythmic drug in addition to their stable, chronic regimen unless it has been at least 5 half-lives since administration at the time of Screening.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
3-period randomized 3-sequence study
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Investigator, Subject, Outcomes Assessor, and Sponsor Blinded; placebo-controlled

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose 1
CRD-4730 Dose 1 Tablet
  • Drug: CRD-4730
    Oral CRD-4730 in tablet form
Experimental
Dose 2
CRD 4730 Dose 2 Tablet
  • Drug: CRD-4730
    Oral CRD-4730 in tablet form
Placebo Comparator
Dose 3
Placebo tablet to match CRD-4730
  • Drug: Placebo
    Placebo to match CRD-4730 in tablet form

Recruiting Locations

Cardurion Investigative Site
San Francisco, California 94143

Cardurion Investigative Site
Morrisville, North Carolina 27560

Cardurion Investigative Site
Houston, Texas 77030

Cardurion Investigative Site
Salt Lake City, Utah 84113

Cardurion Investigative Site
Madison, Wisconsin 53792

More Details

Status
Recruiting
Sponsor
Cardurion Pharmaceuticals, Inc.

Study Contact

Cardurion
617-863-8088
infoCPVT@cardurion.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.