Clinical trial NCT02300558: Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3
Official title: A Phase 3, Single-Blind Study to Evaluate the Effect of Eleclazine (GS-6615) on Shortening of the QT Interval, Safety, and Tolerability in Subjects With Long QT Syndrome Type 3
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Long QT Syndrome Type 3
Keywords: Type 3 long QT syndrome (LQT3)
Long QT syndrome
Congenital long QT
Sudden cardiac death
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-11-25
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the effect of oral eleclazine on mean daytime QTcF interval after 24 weeks of treatment with elecalzine in participants with long QT syndrome Type 3. During the single-blind treatment period (24 weeks), participants will receive eleclazine and/or eleclazine placebo. Following the single-blind treatment period, participants who have not permanently discontinued study drug will be eligible, at the discretion of the investigator, to continue receiving eleclazine during an open-label extension (OLE) phase.


Eligibility criteria: Key Inclusion Criteria:

* Individuals with an established diagnosis of LQT3 (by genotype testing)
* Mean (of triplicate) QTc interval ≥ 480 msec (or ≥ 460 msec, for individuals who are currently taking ranolazine or Class I antiarrhythmic drugs such as mexiletine) at 3 or more time points, determined by standard 12-lead ECG, at screening

Key Exclusion Criteria:

* Known mutations associated with type 1 long QT syndrome (LQT1) or type 2 long QT syndrome (LQT2)
* Known or suspected history of seizures or epilepsy
* History of heart failure defined as New York Heart Association (NYHA) Class IV and/or known left ventricular ejection fraction (EF) ≤ 45%
* Body mass index (BMI) ≥ 40 kg/m\^2 at screening
* Severe renal impairment at screening (defined as an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m\^2, using the 4 Variable Modification of Diet in Renal Disease (MDRD) equation, as determined by the study center)
* Abnormal liver function tests at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 x upper limit of normal (ULN), or total bilirubin \> 1.5 x ULN
* An aborted cardiac arrest (ACA), implantable cardioverter-defibrillator (ICD) implantation, syncopal episode, or appropriate ICD therapy within 3 months prior to screening
* Any other condition or circumstance that in the opinion of the investigator would preclude compliance with the study protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Change From Baseline in Mean Daytime QT Interval in Lead V5 Corrected for Heart Rate Using the Fridericia Formula (QTcF) Interval to Week 24 (Based on Standard 12-lead ECG Data)
timeFrame: Baseline; Week 24
Secondary outcomes:
measure: Change From Baseline in Mean Daytime QTcF Interval (AUC0-6/6) to Week 12 (Lead V5; Standard 12-lead ECG)
timeFrame: Baseline; Week 12
measure: Change From Baseline in Mean Daily (Daytime and Nocturnal) QTcF Interval to Week 24 (Lead V5; Holter)
timeFrame: Baseline; Week 24
measure: Change From Baseline in Mean Nocturnal QTcF Interval to Week 24 (Lead V5; Holter)
timeFrame: Baseline; Week 24
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Nantes
country: France
facility: L'institut Du Thorax Nantes
city: Paris
country: France
facility: Groupe Hospitalier Bichat Claude Bernard
city: Saint-Pierre
country: France
facility: CHU Réunion Sud
city: München
country: Germany
facility: LMU Klinikum der Universität München
city: Tel-Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri IRCCS
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum Amsterdam
city: London
country: United Kingdom
facility: Barts and The London School of Medicine and Dentistry
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: