Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3

Phase 3TerminatedNCT02300558

Gilead Sciences41 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Long QT Syndrome Type 3

Interventions

Eleclazine

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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.

Locations (12)

Mayo Clinic Rochester

Rochester, Minnesota, United States

NYU Langone Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

L'institut Du Thorax Nantes

Nantes, France

Groupe Hospitalier Bichat Claude Bernard

Paris, France

CHU Réunion Sud

Saint-Pierre, France

LMU Klinikum der Universität München

München, Germany

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Fondazione Salvatore Maugeri IRCCS

Pavia, Italy

...and 2 more locations

Outcomes

Primary Outcomes

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)

* Baseline was the Day 1 value. * QTcF is corrected QT interval using Fridericia's formula. QTcF = QT/cube root (RR), where RR is in seconds. * AUC0-6 for QTcF was calculated using the trapezoidal rule, mean of triplicate values, and actual time (latest of triplicate times). * Mean daytime QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from dosing to the 6 hour postdose time point.

Time frame: Baseline; Week 24

Secondary Outcomes

Change From Baseline in Mean Daytime QTcF Interval (AUC0-6/6) to Week 12 (Lead V5; Standard 12-lead ECG)

* Baseline was the Day 1 value. * QTcF is corrected QT interval using Fridericia's formula. QTcF = QT/cube root (RR), where RR is in seconds. * AUC0-6 for QTcF was calculated using the trapezoidal rule, mean of triplicate values, and actual time (latest of triplicate times) . * Mean daytime QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from dosing to the 6 hour postdose time point.

Time frame: Baseline; Week 12

Change From Baseline in Mean Daily (Daytime and Nocturnal) QTcF Interval to Week 24 (Lead V5; Holter)

* Baseline was the Day 1 value. * QTcF is corrected QT interval using Fridericia's formula. QTcF = QT/cube root (RR), where RR is in seconds. * Mean daytime QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from the first nonmissing nominal time point to the last nonmissing nominal time point, from predose to 6 hours postdose. Mean nocturnal QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from the first nonmissing nominal time point to the last nonmissing nominal time point, from midnight to 6:00 AM. Daily was computed as the average of daytime (AUC0-6/6) and nocturnal (AUC0-6/6), with both values required to compute the average.

Time frame: Baseline; Week 24

Change From Baseline in Mean Nocturnal QTcF Interval to Week 24 (Lead V5; Holter)

* Baseline was the Day 1 value. * QTcF is corrected QT interval using Fridericia's formula. QTcF = QT/cube root (RR), where RR is in seconds. * Mean nocturnal QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from the first nonmissing nominal time point to the last nonmissing nominal time point, from midnight to 6:00 AM.

Time frame: Baseline; Week 24