Evaluating Ventricular Arrhythmia in Subjects With Implantable Cardioverter Defibrillator or Cardiac Resynchronization Therapy-Defibrillator

Phase 2

Completed

Conditions: Ventricular Arrhythmia

Interventions: Drug: Eleclazine
Drug: Placebo to match eleclazine

Registration Number: NCT02104583

Lead Sponsor: Gilead Sciences

Brief Summary: The primary objective of this study is to evaluate the effect of eleclazine (GS-6615) compared to placebo on the overall occurrence of appropriate implantable cardioverter-defibrillator (ICD) interventions (antitachycardia pacing \[ATP\] or shock) in adults with ICD or cardiac resynchronization therapy-defibrillator (CRT-D).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 313

Inclusion Criteria

Have an ICD or CRT-D implanted for primary or secondary prevention and at least one ICD intervention for ventricular tachycardia/ventricular fibrillation (VT/VF) [shock or ATP] within 60 days prior to screening or a documented VT/VF episode (prior to implantation) within 60 days prior to screening
Use of highly effective contraception methods if female of childbearing potential or sexually active male
Must be hemodynamically stable

Key

Exclusion Criteria

New York Heart Association (NYHA) Class IV heart failure
Myocardial infarction, unstable angina, coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) within 4 weeks prior to screening or during the screening period before randomization
Hemodynamically significant primary obstructive valvular disease
History of congenital heart disease
Inherited arrhythmia such as Brugada syndrome. Individuals with long QT syndrome Type 3 (LQT-3) or hypertrophic cardiomyopathy (HCM) may be considered.
Individuals who are being considered for cardiac transplantation and are on a cardiac transplant list
History of seizures or epilepsy
Cardiac ablation within 3 months prior to screening or planned cardiac ablation during the study
Severe renal impairment
Abnormal liver function tests
Currently taking Class I and Class III antiarrhythmic drugs; such medications should be discontinued 5 half-lives (or 28 days for chronic use of amiodarone) prior to randomization
Currently taking drugs or products that are strong inhibitors or inducers of CYP3A; such medications should be discontinued 5 half-lives prior to randomization
Currently taking ranolazine; ranolazine should be discontinued at least 7 days prior to randomization
Females who are pregnant or are breastfeeding
Individuals with a subcutaneous ICD
Body mass index (BMI) ≥ 36 kg/m^2

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Eleclazine 3 mg	Eleclazine	Participants will receive a single loading dose of eleclazine 30 mg on Day 1, followed by eleclazine 3 mg daily as maintenance for up to approximately 20 months.
Eleclazine 6 mg	Eleclazine	Participants will receive a single loading dose of eleclazine 30 mg on Day 1, followed by eleclazine 6 mg daily as maintenance for up to approximately 20 months.
Placebo	Placebo to match eleclazine	Participants will receive a single loading dose of placebo to match eleclazine on Day 1, followed by placebo to match eleclazine once daily for up to approximately 20 months.

Primary Outcome Measures

Name	Time	Method
Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24	Randomization up to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study	Randomization up to 22 months
Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring	Baseline to Week 12	PVC count per 48 hours was obtained from cECG readings at Baseline and Week 12. Change in PVC from baseline was measured in units of number of episodes/48 hours. Change from baseline was calculated as the value at Week 12 minus the value at Baseline.
Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death	From first dose of study drug up to 22 months	CV hospitalizations, CV ER visits, and CV deaths were determined through the adjudication by the CEC. The events that were adjudicated as undetermined were considered cardiovascular related. For each participant, the time from the first dose of study drug to the first CV hospitalization or CV ER visit through the last day on study or, in absence of CV hospitalizations or CV ER visits, to a CV death were derived as (first event date - first dose date + 1). The participants without CV hospitalizations, CV ER visits, or CV death were censored at the last day on study. As planned, data was reported only for Cohort 2 and combined Cohorts 1 and 2. Time to first occurrence of CV hospitalization, ER visit, or CV death was analyzed using KM estimates.
Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring	Baseline to Week 12	The count of nsVTs per 48 hours was obtained from cECG readings at Baseline and Week 12. Change in nsVT from baseline was measured in units of number of episodes/48 hours. Change from baseline was calculated as the value at Week 12 minus the value at Baseline.
Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study	Randomization up to Week 24; Randomization up to end of study (up to 22 months)
Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study	Randomization up to Week 24; Randomization up to end of study (up to 22 months)	An electrical storm was defined as ≥ 3 separate episodes of ventricular arrhythmia within a 24-hour period terminated by ICD.
Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study	Randomization up to Week 24; Randomization up to end of study (up to 22 months)
Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF)	Baseline to Week 12; Baseline to Week 24	LVEF is a measure of how much blood is pumped out of the left ventricle of the heart. Change from baseline was calculated as the value at Week 12 or 24 minus the value at Baseline.
Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death	From first dose of study drug up to 22 months	CV deaths were determined through the adjudication by an external independent clinical event committee (CEC). The deaths that were adjudicated as undetermined were considered cardiovascular related. For each participant, the time from the first dose of study drug to the beginning of the earliest appropriate ICD intervention through the last day on study or, in absence of appropriate ICD interventions, to a CV death was derived as (first event date - first dose date + 1). The participants without appropriate ICD interventions or CV death were censored at the last day on study. As planned, data was reported only for Cohort 2 and combined Cohorts 1 and 2. Time to first occurrence of an appropriate ICD interventions or CV death was analyzed using Kaplan-Meier (KM) estimates.

Trial Locations

Locations (84): Cardiovascular Associates of Mesa
🇺🇸
Mesa, Arizona, United States
Long Beach Memorial Hospital
🇺🇸
Long Beach, California, United States
Good Samaritan Hospital
🇺🇸
Los Angeles, California, United States
Radin Cardiovascular Medical Associates
🇺🇸
Newport Beach, California, United States
Regional Cardiology Associates
🇺🇸
Sacramento, California, United States
South Denver Cardiology Associates, PC
🇺🇸
Littleton, Colorado, United States
Atlantic Clinical Research Collaborative
🇺🇸
Atlantis, Florida, United States
Clearwater Cardiovascular and Interventional Consultants
🇺🇸
Clearwater, Florida, United States
Coastal Cardiology Consultants PA dba Heart and Vascular Institute of Florida
🇺🇸
Clearwater, Florida, United States
The Heart Institute at Largo
🇺🇸
Largo, Florida, United States
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Cardiovascular Associates of Mesa
🇺🇸Mesa, Arizona, United States