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

Ventricular Arrhythmia Clinical Trial

— TEMPO  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02104583
• Other study ID #: GS-US-356-0101
• Secondary ID: 2013-004430-15
• Status: Completed
• Phase: Phase 2
• Start date: September 2014
• Est. completion date: October 2016

Study information

• Verified date: March 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 313
• Est. completion date: October 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Ventricular Arrhythmia

Intervention

Drug:
• Eleclazine
Eleclazine tablets administered orally
• Placebo to match eleclazine
Placebo to match eleclazine tablets administered orally

Locations

Country	Name	City	State
Canada	QEII Health Sciences Centre	Halifax
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Chum Hotel Dieu	Montreal	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke CHUS	Sherbrooke	Quebec
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Charles University Hospital Královské Vinohrady	Prague
Denmark	Aalborg University Hospital	Aalborg
Denmark	Rigshospitalet, The Heart Center	Copenhagen
Denmark	Gentofte Hospitak, Deparment of Cardiology	Hellerup
Denmark	Odense University Hospital/Department of Cardiology	Odense C
Germany	Vivantes Humboldt Klinikum	Berlin
Germany	University Medical Center Goettingen	Goettingen
Germany	University of Heidelberg	Heidelberg
Germany	Medizinische Klinik und Poliklinik I Abteilung für Kardiologie	Munich
Germany	Klinikum der Universität Regensburg	Regensburg
Germany	Gemeinschaftspraxis für Innere Medizin	Riesa
Hungary	State Hospital for Cardiology	Balatonfüred
Hungary	Budai Irgalmasrendi Kórház	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Zala Megyei Kórház	Zalaegerszeg
Israel	HaEmek Medical Center	Afula
Israel	Rambam Health Care Campus	Haifa
Israel	Tel Aviv University/Meir Medical Center	Israel
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Galilee Medical Center	Nahariya
Israel	Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Amphia ziekenhuis	Breda
Netherlands	Catharina ziekenhuis	Eindhoven
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	St.Antonius Hospital	Nieuwegein
Netherlands	Isala	Zwolle
Poland	Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach Górnosla	Katowice
Poland	Collegium Medicum Uniwersytetu Jagiellonskiego	Kraków
Poland	Medical University of Lodz	Lodz
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Andrzej Lubinski	Lódz
Poland	Mc Tronik Specjalistyczny Gabinet Kontroli Stymulatorow Serca Dr N. Med. Michal Chudzik	Lódz
Poland	NZOZ Sopockie Centrum badan Kardiolog.ProCordis pawel Miekus	Sopot
Poland	Indywidualna Specjalistyczna Praktyka Lekarska Jaroslaw Kazmierczak	Szczecin
Poland	Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego	Warsaw
Poland	Szpital Wolski im Dr Anny Gostynskiej SP ZOZ	Warszawa
Poland	Warszawski Uniwersytet Medyczny	Warszawa
Poland	Medical University Wroclaw	Wroclaw
United States	New Mexico Hear Institute	Albuquerque	New Mexico
United States	Athens Regional Specialty Services	Athens	Georgia
United States	Atlantic Clinical Research Collaborative	Atlantis	Florida
United States	Seton Heart Institute	Austin	Texas
United States	New York Methodist Hospital	Brooklyn	New York
United States	The University of Vermont Medical Center	Burlington	Vermont
United States	Capital Area Research	Camp Hill	Pennsylvania
United States	Aultman Hospital	Canton	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
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	Ohiohealth Corporation	Columbus	Ohio
United States	Cardiovascular Research Institute of Dallas	Dallas	Texas
United States	Durham VA Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Virginia Heart Group Ltd	Falls Church	Virginia
United States	Great Falls Clinic	Great Falls	Montana
United States	West Houston Area Clinical Trial Consultants	Houston	Texas
United States	Volunteer Research Group	Knoxville	Tennessee
United States	The Heart Institute at Largo	Largo	Florida
United States	South Denver Cardiology Associates, PC	Littleton	Colorado
United States	Long Beach Memorial Hospital	Long Beach	California
United States	Good Samaritan Hospital	Los Angeles	California
United States	Stroobants Cardiovascular Center	Lynchburg	Virginia
United States	Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Cardiovascular Associates of Mesa	Mesa	Arizona
United States	Mid Michigan Medical Center - Midland	Midland	Michigan
United States	Radin Cardiovascular Medical Associates	Newport Beach	California
United States	Methodist Physicians Clinic Heart Consultants	Omaha	Nebraska
United States	Charlotte Heart and Vascular Institute	Port Charlotte	Florida
United States	Carilion Roanoke Memorial Hospital	Roanoke	Virginia
United States	Regional Cardiology Associates	Sacramento	California
United States	Michigan Cardiovascular Institute	Saginaw	Michigan
United States	Washington Adventist Hospital	Takoma Park	Maryland
United States	Care New England Health Care, Kent Hospital	Warwick	Rhode Island
United States	CardioVascular Institute	Wormleysburg	Pennsylvania
United States	Florida Medical Clinic PA	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Denmark,  Germany,  Hungary,  Israel,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study		Randomization up to 22 months
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.	Baseline to Week 12
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.	Baseline to Week 12
Secondary	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)
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.	Randomization up to Week 24; Randomization up to end of study (up to 22 months)
Secondary	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)
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.	Baseline to Week 12; Baseline to Week 24
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.	From first dose of study drug up to 22 months
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.	From first dose of study drug up to 22 months