CPVT1, Heart Defects, Congenital, Heart Diseases, Ventricular Tachycardia
Conditions
Keywords
CaMKII, Catecholaminergic polymorphic VT, Ventricular Tachycardia, CRD-4730
Brief summary
This is a Phase 2, multicenter, double-blind, sponsor unblinded, placebo-controlled, single-dose clinical study of CRD-4730 to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CRD-4730 when administered as single oral doses to participants with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The study will have 2 cohorts in which participants with CPVT will participate in a 3-period, randomized 2-sequence study. Each participant will receive 2 different doses of CRD-4730 and 1 dose of matching placebo, with each study drug administered as a single dose.
Interventions
DRUGCRD-4730
Oral CRD-4730 in capsule form
DRUGPlacebo
Placebo to match CRD-4730 in capsule form
Sponsors
Cardurion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigator and Subject Blinded, Sponsor Unblinded; Placebo-controlled
Intervention model description
3-period randomized 2-sequence study
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Males or Females ≥18 years of age, at screening. 2. Confirmed CPVT diagnosis, based on genetic screening for a known RyR2 mutation and a clinical phenotype consistent with CPVT at screening. 3. The participant can perform an EST during which frequent premature ventricular contraction (PVCs) (≥10 per minute), ventricular bigeminy, or higher-grade VA (equivalent to a VA score ≥2) are identified by the investigator. 4. Stable doses of any anti-arrhythmic medication, except amiodarone, for 4 weeks prior to screening. 5. Adhere to all contraceptive criteria.
Exclusion criteria
1. Clinically significant structural heart disease, diagnosis of heart failure, or clinically significant coronary artery disease. 2. History of a myocardial infarction, cerebrovascular accident, or transient ischemic attack within 3 months of screening. 3. History of malignancy within the past 5 years at screening (except successfully treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or cervical carcinoma in situ). 4. Female participant that is pregnant or lactating/ breastfeeding, or has plans to do so during the study or within 3 months following last dose of study drug. 5. Use of amiodarone with 3 months prior to screening. NOTE: other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events (TEAEs) | Baseline to Day 22 | The number of participants with TEAEs including drug-related AEs, serious AEs (SAEs), and AEs leading to study drug discontinuation will be assessed. |
| Changes in Laboratory Assessments | Baseline to Day 15 | The number of participants who have normal/ abnormal values at Baseline compared to normal/ abnormal values post-Baseline will be assessed for hematology, serum chemistry and urinalysis. |
| Changes in Vital Signs Measurement: Systolic and Diastolic blood pressure | Baseline to Day 15 | Percent change from Baseline to post Baseline will be assessed for systolic and diastolic blood pressure |
| Changes in Vital Signs Measurement: Pulse Rate | Baseline to Day 15 | Percent change from Baseline to post Baseline will be assessed for pulse rate |
| Changes in Vital Signs Measurement: Respiratory Rate | Baseline to Day 15 | Percent change from Baseline to post Baseline will be assessed for respiratory rate |
| Changes in Vital Signs Measurement: Body Temperature | Baseline to Day 15 | Percent change from Baseline to post Baseline will be assessed for body temperature |
| Changes in Physical Exam | Baseline to Day 22 | General physical exams will be carried out to detect any abnormalities in the cardiovascular, respiratory and other body systems |
| Changes in Electrocardiogram (ECG) Measurements | Baseline to Day 22 | Number of participants who have normal/abnormal ECG measurements at Baseline will be compared to normal/abnormal ECG measurement post Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST) | Baseline to Day 1 | The VA score is a physician administered score on a scale of 0-5 with higher numbers being worse. |
| Assessment of PK effect | Baseline through Day 15 | Plasma concentrations of CRD-4730 over time for each treatment period |
Countries
Canada, France, Italy, United States
Contacts
STUDY_DIRECTORJason Homsy, M.D., Ph.D.
Executive Medical Director
Outcome results
None listed