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

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)

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).

Study Overview

• Status: Completed
• Conditions: Ventricular Arrhythmia
• Intervention / Treatment: Drug: Eleclazine; Drug: Placebo to match eleclazine

• Study Type: Interventional
• Enrollment (Actual): 313
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Halifax, Canada, B3H 3A7
    • QEII Health Sciences Centre
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • CHUM Hôtel Dieu
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke CHUS
• Czechia
  • Olomouc, Czechia
    • Fakultni Nemocnice Olomouc
  • Prague, Czechia
    • Charles University Hospital Královské Vinohrady
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital
  • Copenhagen, Denmark
    • Rigshospitalet, The Heart Center
  • Hellerup, Denmark, 2900
    • Gentofte Hospitak, Deparment of Cardiology
  • Odense C, Denmark, 5000
    • Odense University Hospital/Department of Cardiology
• Germany
  • Berlin, Germany, 13585
    • Vivantes Humboldt Klinikum
  • Goettingen, Germany
    • University Medical Center Goettingen
  • Heidelberg, Germany, '69120
    • University of Heidelberg
  • Munich, Germany, 81377
    • Medizinische Klinik und Poliklinik I Abteilung für Kardiologie
  • Regensburg, Germany, 93053
    • Klinikum der Universität Regensburg
  • Riesa, Germany, 1587
    • Gemeinschaftspraxis für Innere Medizin
• Hungary
  • Balatonfüred, Hungary, 8231
    • State Hospital for Cardiology
  • Budapest, Hungary, 1027
    • Budai Irgalmasrendi Korhaz
  • Budapest, Hungary, 1122
    • Semmelweis Egyetem
  • Budapest, Hungary, 1134
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Zalaegerszeg, Hungary, 8900
    • Zala Megyei Kórház
• Israel
  • Afula, Israel, 18101
    • HaEmek Medical Center
  • Haifa, Israel, 31096
    • Rambam Health Care Campus
  • Israel, Israel, 44299
    • Tel Aviv University/Meir Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Nahariya, Israel, 22100
    • Galilee Medical Center
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Netherlands
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis
  • Breda, Netherlands
    • Amphia ziekenhuis
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis
  • Maastricht, Netherlands
    • Maastricht University Medical Center
  • Nieuwegein, Netherlands, 3430EM
    • St.Antonius Hospital
  • Zwolle, Netherlands
    • Isala
• Poland
  • Katowice, Poland, 40-635
    • Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach Górnosla
  • Kraków, Poland, 31-501
    • Collegium Medicum Uniwersytetu Jagiellonskiego
  • Lodz, Poland, 91-347
    • Medical University of Lodz
  • Lódz, Poland, 90-553
    • Mc Tronik Specjalistyczny Gabinet Kontroli Stymulatorow Serca Dr N. Med. Michal Chudzik
  • Lódz, Poland, 91-078
    • Indywidualna Specjalistyczna Praktyka Lekarska Andrzej Lubinski
  • Sopot, Poland, 81-717
    • NZOZ Sopockie Centrum badan Kardiolog.ProCordis pawel Miekus
  • Szczecin, Poland, 70-203
    • Indywidualna Specjalistyczna Praktyka Lekarska Jarosław Kaźmierczak
  • Warsaw, Poland, 04-628
    • Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego
  • Warszawa, Poland, 01-211
    • Szpital Wolski im Dr Anny Gostynskiej SP ZOZ
  • Warszawa, Poland, 02-097
    • Warszawski Uniwersytet Medyczny
  • Wroclaw, Poland
    • Medical University Wroclaw
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • CardioVascular Associates of Mesa
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Hospital
    • Los Angeles, California, United States, 90017
      • Good Samaritan Hospital
    • Newport Beach, California, United States, 92663
      • Radin Cardiovascular Medical Associates
    • Sacramento, California, United States, 95819
      • Regional Cardiology Associates
  • Colorado
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates, PC
  • Florida
    • Atlantis, Florida, United States, 33462
      • Atlantic Clinical Research Collaborative
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular and Interventional Consultants
    • Clearwater, Florida, United States, 33756
      • Coastal Cardiology Consultants PA dba Heart and Vascular Institute of Florida
    • Largo, Florida, United States, 33770
      • The Heart Institute at Largo
    • Port Charlotte, Florida, United States, 33952
      • Charlotte Heart and Vascular Institute
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Clinic PA
  • Georgia
    • Athens, Georgia, United States, 30606
      • Athens Regional Specialty Services
  • Maryland
    • Takoma Park, Maryland, United States, 20912
      • Washington Adventist Hospital
  • Michigan
    • Midland, Michigan, United States, 48670
      • Mid Michigan Medical Center - Midland
    • Saginaw, Michigan, United States, 48601
      • Michigan Cardiovascular Institute
  • Montana
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Physicians Clinic Heart Consultants
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • New Mexico Hear Institute
  • New York
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center
  • Ohio
    • Canton, Ohio, United States, 44708
      • Aultman Hospital
    • Columbus, Ohio, United States, 43214
      • OhioHealth Corporation
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Capital Area Research
    • Wormleysburg, Pennsylvania, United States, 17043
      • Cardiovascular Institute
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Care New England Health Care, Kent Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
  • Texas
    • Austin, Texas, United States, 78705
      • Seton Heart Institute
    • Dallas, Texas, United States, 75231
      • Cardiovascular Research Institute of Dallas
    • Houston, Texas, United States, 77094
      • West Houston Area Clinical Trial Consultants
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Falls Church, Virginia, United States, 22042
      • Virginia Heart Group Ltd
    • Lynchburg, Virginia, United States, 24501
      • Stroobants Cardiovascular Center
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Memorial Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic Research Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline to Week 12
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.	Baseline to Week 12
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	An electrical storm was defined as ≥ 3 separate episodes of ventricular arrhythmia within a 24-hour period terminated by ICD.	Randomization up to Week 24; Randomization up to end of study (up to 22 months)
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)	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.	Baseline to Week 12; Baseline to Week 24
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.	From first dose of study drug up to 22 months
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.	From first dose of study drug up to 22 months

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (Estimate): April 4, 2014

Study Record Updates

• Last Update Posted (Actual): April 9, 2019
• Last Update Submitted That Met QC Criteria: March 19, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: shock; VT; Ventricular Tachycardia; Ventricular Fibrillation; ATP; VF
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac
• Other Study ID Numbers: GS-US-356-0101; 2013-004430-15 (EudraCT Number)