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

Long QT Syndrome Type 3 Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02300558
• Other study ID #: GS-US-372-1234
• Secondary ID: 2014-000042-30
• Status: Terminated
• Phase: Phase 3
• First received: November 21, 2014
• Last updated: December 12, 2017
• Start date: December 17, 2014
• Est. completion date: February 15, 2017

Study information

• Verified date: December 2017
• 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: February 15, 2017
• Est. primary completion date: December 12, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Long QT Syndrome
• Long QT Syndrome Type 3
• Syndrome

Intervention

Drug:
• Eleclazine
Tablets administered orally
• Eleclazine placebo
Tablets administered orally

Locations

Country	Name	City	State
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia
France	L'institut Du Thorax Nantes	Nantes
France	Groupe Hospitalier Bichat Claude Bernard	Paris
France	CHU Réunion Sud	Saint-Pierre
Germany	LMU Klinikum der Universität München	München
Israel	Tel Aviv Sourasky Medical Center	Tel-Aviv
Italy	Fondazione Salvatore Maugeri IRCCS	Pavia
Netherlands	Academisch Medisch Centrum Amsterdam	Amsterdam
United Kingdom	Barts and The London School of Medicine and Dentistry	London
United States	NYU Langone Medical Center	New York	New York
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Israel,  Italy,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline; Week 24
Secondary	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.	Baseline; Week 12
Secondary	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.	Baseline; Week 24
Secondary	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.	Baseline; Week 24