Ventricular Arrhythmia
Conditions
Keywords
VT, VF, Ventricular Tachycardia, Ventricular Fibrillation, shock, ATP
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).
Interventions
DRUGEleclazine
Eleclazine tablets administered orally
DRUGPlacebo to match eleclazine
Placebo to match eleclazine tablets administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 Appropriate ICD Interventions (ATP or Shock) Through End of Study | Randomization 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. |
| 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. |
| 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) | — |
Countries
Canada, Czechia, Denmark, Germany, Hungary, Israel, Netherlands, Poland, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Europe, and Asia. The first participant was screened on 12 September 2014. The last study visit occurred on 14 October 2016.
Pre-assignment details
389 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Eleclazine 3 mg Participants received single loading dose of eleclazine 30 mg (3 x 10 mg tablets) on Day 1, followed by eleclazine 3 mg tablet once daily as maintenance for up to approximately 22 months. | 48 |
| Cohort 1 Placebo Participants received single loading dose of placebo to match eleclazine tablets On Day 1, followed by placebo to match eleclazine tablet once daily for up to approximately 20 months | 46 |
| Cohort 2 Eleclazine 3 mg Participants received single loading dose of eleclazine 30 mg (3 x 10 mg tablets) on Day 1, followed by eleclazine 3 mg tablet once daily as maintenance for up to approximately 14 months. | 70 |
| Cohort 2 Eleclazine 6 mg Participants received single loading dose of eleclazine 30 mg (3 x 10 mg tablets) on Day 1, followed by eleclazine 6 mg (2 x 3 mg tablets) once daily as maintenance for up to approximately 14 months. | 74 |
| Cohort 2 Placebo Participants received single loading dose of placebo to match eleclazine tablets on Day 1, followed by placebo to match eleclazine tablets once daily for up to approximately 14 months. | 75 |
| Total | 313 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 6 | 6 | 1 |
| Overall Study | Death | 2 | 1 | 3 | 3 | 5 |
| Overall Study | Investigator's Discretion | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Overall Study | New ICD or CRT-D implanted | 2 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Randomized but Never Treated | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Subject required cardiac ablation | 6 | 4 | 4 | 5 | 4 |
| Overall Study | Subject required prohibited medication | 0 | 1 | 1 | 0 | 1 |
| Overall Study | Withdrew Consent | 3 | 2 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Cohort 1 Eleclazine 3 mg | Cohort 2 Placebo | Cohort 2 Eleclazine 6 mg | Cohort 2 Eleclazine 3 mg | Cohort 1 Placebo |
|---|---|---|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 9.6 | 65 years STANDARD_DEVIATION 10.4 | 64 years STANDARD_DEVIATION 9.4 | 65 years STANDARD_DEVIATION 8.3 | 65 years STANDARD_DEVIATION 10.8 | 64 years STANDARD_DEVIATION 9.6 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 306 Participants | 47 Participants | 73 Participants | 71 Participants | 70 Participants | 45 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 4 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black | 5 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not permitted | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 303 Participants | 47 Participants | 71 Participants | 70 Participants | 70 Participants | 45 Participants |
| Region of Enrollment Canada | 12 Participants | 0 Participants | 6 Participants | 3 Participants | 3 Participants | 0 Participants |
| Region of Enrollment Czechia | 8 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Denmark | 10 Participants | 2 Participants | 1 Participants | 4 Participants | 3 Participants | 0 Participants |
| Region of Enrollment Germany | 24 Participants | 0 Participants | 9 Participants | 7 Participants | 7 Participants | 1 Participants |
| Region of Enrollment Hungary | 35 Participants | 3 Participants | 9 Participants | 10 Participants | 9 Participants | 4 Participants |
| Region of Enrollment Israel | 38 Participants | 9 Participants | 6 Participants | 9 Participants | 6 Participants | 8 Participants |
| Region of Enrollment Netherlands | 12 Participants | 0 Participants | 3 Participants | 5 Participants | 4 Participants | 0 Participants |
| Region of Enrollment Poland | 57 Participants | 6 Participants | 15 Participants | 11 Participants | 18 Participants | 7 Participants |
| Region of Enrollment United States | 117 Participants | 25 Participants | 24 Participants | 24 Participants | 20 Participants | 24 Participants |
| Sex: Female, Male Female | 32 Participants | 4 Participants | 8 Participants | 7 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 280 Participants | 44 Participants | 67 Participants | 66 Participants | 62 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 48 | 26 / 46 | 42 / 70 | 34 / 73 | 33 / 75 |
| serious Total, serious adverse events | 27 / 48 | 25 / 46 | 28 / 70 | 26 / 73 | 26 / 75 |
Outcome results
Primary
Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24
Time frame: Randomization up to 24 weeks
Population: Participants in the Full Analysis Set-ICD \[all participants who were randomized into the study and received at least 1 dose of study medication, restricted to participants who had at least 1 postbaseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) interrogation\] with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Eleclazine 3 mg | Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24 | 3.3 events | Standard Deviation 6.99 |
| Cohort 1 Placebo | Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24 | 1.9 events | Standard Deviation 3.79 |
| Cohort 2 Eleclazine 3 mg | Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24 | 2.6 events | Standard Deviation 6.8 |
| Cohort 2 Eleclazine 6 mg | Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24 | 1.1 events | Standard Deviation 2.09 |
| Cohort 2 Placebo | Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24 | 1.5 events | Standard Deviation 3.92 |
| Cohorts 1 and 2, Eleclazine 3 mg | Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24 | 2.8 events | Standard Deviation 6.86 |
| Cohorts 1 and 2, Placebo | Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24 | 1.7 events | Standard Deviation 3.86 |
Comparison: The primary analysis of overall occurrence of appropriate ICD interventions through Week 24 was performed using a generalized linear model assuming a negative binomial distribution and log link. This model included terms for treatment, implanted device (ICD or CRT-D) and region \[US or rest of world (ROW)\].p-value: 0.15295% CI: [0.86, 2.71]generalized linear model
Comparison: The primary analysis of overall occurrence of appropriate ICD interventions through Week 24 was performed using a generalized linear model assuming a negative binomial distribution and log link. This model included terms for treatment, implanted device (ICD or CRT-D) and region \[US or ROW\].p-value: 0.66295% CI: [0.34, 1.97]generalized linear model
Comparison: The primary analysis of overall occurrence of appropriate ICD interventions through Week 24 was performed using a generalized linear model assuming a negative binomial distribution and log link. This model included terms for treatment, implanted device (ICD or CRT-D) and region \[US or ROW.p-value: 0.61895% CI: [0.54, 2.86]generalized linear model
Secondary
Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring
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.
Time frame: Baseline to Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Eleclazine 3 mg | Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring | 44 episodes/48 hours | Standard Deviation 171.6 |
| Cohort 1 Placebo | Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring | -14 episodes/48 hours | Standard Deviation 52.2 |
| Cohort 2 Eleclazine 3 mg | Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring | -67 episodes/48 hours | Standard Deviation 400.4 |
| Cohort 2 Eleclazine 6 mg | Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring | 46 episodes/48 hours | Standard Deviation 388.4 |
| Cohort 2 Placebo | Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring | 2 episodes/48 hours | Standard Deviation 15.1 |
Secondary
Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring
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 frame: Baseline to Week 12
Population: Participants in the Full Analysis Set (all participants who were randomized into the study and received at least 1 dose of study medication) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Eleclazine 3 mg | Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring | 4282 episodes/48 hours | Standard Deviation 17651.5 |
| Cohort 1 Placebo | Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring | -2347 episodes/48 hours | Standard Deviation 8498.8 |
| Cohort 2 Eleclazine 3 mg | Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring | -594 episodes/48 hours | Standard Deviation 13323 |
| Cohort 2 Eleclazine 6 mg | Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring | -39 episodes/48 hours | Standard Deviation 13575 |
| Cohort 2 Placebo | Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring | 1541 episodes/48 hours | Standard Deviation 11117.7 |
Secondary
Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF)
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 frame: Baseline to Week 12; Baseline to Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 Eleclazine 3 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Baseline | 35 percentage of blood | Standard Deviation 12.8 |
| Cohort 1 Eleclazine 3 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 24 | 1 percentage of blood | Standard Deviation 12.3 |
| Cohort 1 Eleclazine 3 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 12 | 3 percentage of blood | Standard Deviation 8.1 |
| Cohort 1 Placebo | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Baseline | 38 percentage of blood | Standard Deviation 12.4 |
| Cohort 1 Placebo | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 24 | 2 percentage of blood | Standard Deviation 8.2 |
| Cohort 1 Placebo | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 12 | 3 percentage of blood | Standard Deviation 6.2 |
| Cohort 2 Eleclazine 3 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 24 | 3 percentage of blood | Standard Deviation 10 |
| Cohort 2 Eleclazine 3 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Baseline | 38 percentage of blood | Standard Deviation 12.1 |
| Cohort 2 Eleclazine 3 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 12 | 3 percentage of blood | Standard Deviation 9.1 |
| Cohort 2 Eleclazine 6 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 24 | 1 percentage of blood | Standard Deviation 10.7 |
| Cohort 2 Eleclazine 6 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 12 | 3 percentage of blood | Standard Deviation 8.2 |
| Cohort 2 Eleclazine 6 mg | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Baseline | 38 percentage of blood | Standard Deviation 13.3 |
| Cohort 2 Placebo | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 24 | 0 percentage of blood | Standard Deviation 8.3 |
| Cohort 2 Placebo | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Baseline | 40 percentage of blood | Standard Deviation 13.5 |
| Cohort 2 Placebo | Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) | Change at Week 12 | 1 percentage of blood | Standard Deviation 8.2 |
Secondary
Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study
Time frame: Randomization up to 22 months
Population: Participants in the Full Analysis Set-ICD with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Eleclazine 3 mg | Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study | 5.0 events | Standard Deviation 7.92 |
| Cohort 1 Placebo | Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study | 7.2 events | Standard Deviation 20.89 |
| Cohort 2 Eleclazine 3 mg | Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study | 3.8 events | Standard Deviation 8.82 |
| Cohort 2 Eleclazine 6 mg | Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study | 1.2 events | Standard Deviation 2.11 |
| Cohort 2 Placebo | Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study | 2.0 events | Standard Deviation 5.55 |
| Cohorts 1 and 2, Eleclazine 3 mg | Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study | 4.3 events | Standard Deviation 8.45 |
| Cohorts 1 and 2, Placebo | Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study | 4.0 events | Standard Deviation 13.75 |
Secondary
Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study
An electrical storm was defined as ≥ 3 separate episodes of ventricular arrhythmia within a 24-hour period terminated by ICD.
Time frame: Randomization up to Week 24; Randomization up to end of study (up to 22 months)
Population: Participants in the Full Analysis Set-ICD with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 Eleclazine 3 mg | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.15 events | Standard Deviation 0.545 |
| Cohort 1 Eleclazine 3 mg | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.21 events | Standard Deviation 0.582 |
| Cohort 1 Placebo | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.15 events | Standard Deviation 0.631 |
| Cohort 1 Placebo | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.63 events | Standard Deviation 2.037 |
| Cohort 2 Eleclazine 3 mg | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.23 events | Standard Deviation 0.843 |
| Cohort 2 Eleclazine 3 mg | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.35 events | Standard Deviation 1.041 |
| Cohort 2 Eleclazine 6 mg | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.03 events | Standard Deviation 0.164 |
| Cohort 2 Eleclazine 6 mg | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.03 events | Standard Deviation 0.164 |
| Cohort 2 Placebo | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.09 events | Standard Deviation 0.408 |
| Cohort 2 Placebo | Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.12 events | Standard Deviation 0.614 |
Secondary
Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study
Time frame: Randomization up to Week 24; Randomization up to end of study (up to 22 months)
Population: Participants in the Full Analysis Set-ICD with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 Eleclazine 3 mg | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.31 events | Standard Deviation 1.613 |
| Cohort 1 Eleclazine 3 mg | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.17 events | Standard Deviation 0.753 |
| Cohort 1 Placebo | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.15 events | Standard Deviation 0.515 |
| Cohort 1 Placebo | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.41 events | Standard Deviation 2.072 |
| Cohort 2 Eleclazine 3 mg | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.16 events | Standard Deviation 0.779 |
| Cohort 2 Eleclazine 3 mg | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.14 events | Standard Deviation 0.772 |
| Cohort 2 Eleclazine 6 mg | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.12 events | Standard Deviation 6.22 |
| Cohort 2 Eleclazine 6 mg | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.14 events | Standard Deviation 0.631 |
| Cohort 2 Placebo | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through Week 24 | 0.39 events | Standard Deviation 2.283 |
| Cohort 2 Placebo | Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study | Total Number of Events Through End of Study | 0.43 events | Standard Deviation 2.395 |
Secondary
Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study
Time frame: Randomization up to Week 24; Randomization up to end of study (up to 22 months)
Population: Participants in the Full Analysis Set-ICD with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 Eleclazine 3 mg | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through End of Study | 5.98 events | Standard Deviation 8.907 |
| Cohort 1 Eleclazine 3 mg | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through Week 24 | 3.56 events | Standard Deviation 7.554 |
| Cohort 1 Placebo | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through End of Study | 7.83 events | Standard Deviation 20.949 |
| Cohort 1 Placebo | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through Week 24 | 2.07 events | Standard Deviation 3.974 |
| Cohort 2 Eleclazine 3 mg | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through Week 24 | 2.74 events | Standard Deviation 6.825 |
| Cohort 2 Eleclazine 3 mg | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through End of Study | 4.07 events | Standard Deviation 9.088 |
| Cohort 2 Eleclazine 6 mg | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through Week 24 | 1.44 events | Standard Deviation 2.779 |
| Cohort 2 Eleclazine 6 mg | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through End of Study | 1.56 events | Standard Deviation 2.794 |
| Cohort 2 Placebo | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through Week 24 | 1.61 events | Standard Deviation 3.952 |
| Cohort 2 Placebo | Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study | Total Number of Events Through End of Study | 2.17 events | Standard Deviation 5.574 |
Secondary
Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death
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.
Time frame: From first dose of study drug up to 22 months
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 Eleclazine 3 mg | Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death | 252.0 days |
| Cohort 1 Placebo | Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death | NA days |
| Cohort 2 Eleclazine 3 mg | Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death | NA days |
| Cohort 2 Eleclazine 6 mg | Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death | 243.0 days |
| Cohort 2 Placebo | Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death | 265.0 days |
Secondary
Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death
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.
Time frame: From first dose of study drug up to 22 months
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 Eleclazine 3 mg | Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death | NA days |
| Cohort 1 Placebo | Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death | NA days |
| Cohort 2 Eleclazine 3 mg | Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death | NA days |
| Cohort 2 Eleclazine 6 mg | Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death | NA days |
| Cohort 2 Placebo | Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death | NA days |