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

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ClinicalTrials.gov Identifier: NCT02104583
Recruitment Status : Completed
First Posted : April 4, 2014
Results First Posted : April 9, 2019
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Ventricular Arrhythmia Drug: Eleclazine Drug: Placebo to match eleclazine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 313 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose Ranging, Parallel Group Study to Evaluate the Effect of GS-6615 on Ventricular Arrhythmia in Subjects With Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronization Therapy-Defibrillator (CRT-D)
Actual Study Start Date : September 2014
Actual Primary Completion Date : September 2016
Actual Study Completion Date : October 2016


Arm Intervention/treatment
Experimental: Eleclazine 3 mg
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.
Drug: Eleclazine
Eleclazine tablets administered orally
Other Name: GS-6615

Experimental: Eleclazine 6 mg
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.
Drug: Eleclazine
Eleclazine tablets administered orally
Other Name: GS-6615

Placebo Comparator: Placebo
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.
Drug: Placebo to match eleclazine
Placebo to match eleclazine tablets administered orally




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study [ Time Frame: Randomization up to 22 months ]
  2. Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring [ Time Frame: 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.

  3. Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring [ Time Frame: 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.

  4. 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) ]
  5. Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study [ Time Frame: 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.

  6. 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) ]
  7. Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 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.

  8. Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death [ Time Frame: 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.

  9. Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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/Exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02104583


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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02104583     History of Changes
Other Study ID Numbers: GS-US-356-0101
2013-004430-15 ( EudraCT Number )
First Posted: April 4, 2014    Key Record Dates
Results First Posted: April 9, 2019
Last Update Posted: April 9, 2019
Last Verified: March 2019
Keywords provided by Gilead Sciences:
VT
VF
Ventricular Tachycardia
Ventricular Fibrillation
shock
ATP