Study to Evaluate the Effect of Eleclazine on QT, Safety, and Tolerability in Participants With Long QT2 Syndrome

A Double-blind, Placebo-controlled Study to Evaluate the Effect of GS-6615 on QT, Safety and Tolerability in Subjects With Long QT2 Syndrome

The primary objective of the study is to evaluate the effect of oral eleclazine (formerly GS-6615) on corrected QT (QTc) interval in participants with long QT2 syndrome.

Study Overview

• Status: Completed
• Conditions: LQT2 Syndrome
• Intervention / Treatment: Drug: Eleclazine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center/Strong Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Participants with an established diagnosis of LQT2 (by genotype testing)
• Mean (of triplicate) QTc interval ≥ 480 msec for at least four out of seven time points, determined by standard 12-lead electrocardiogram (ECG), at screening

Key Exclusion Criteria:

• Known mutations associated with long QT syndrome type 1 or long QT syndrome type 3
• 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) ≥ 36 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eleclazine 24 mg + Eleclazine 48 mg + Placebo; Participants will receive placebo to match eleclazine on Days 1 and 4, eleclazine 24 mg on Day 2 and eleclazine 48 mg on Day 3.	Drug: Eleclazine; Tablets administered orally in a single dose; Other Names: GS-6615; Drug: Placebo; Placebo to match tablets administered orally in a single dose
Experimental: Eleclazine 48 mg + Placebo; Participants will receive placebo to match eleclazine on Days 1, 2 and 4, and eleclazine 48 mg on Day 3.	Drug: Eleclazine; Tablets administered orally in a single dose; Other Names: GS-6615; Drug: Placebo; Placebo to match tablets administered orally in a single dose
Placebo Comparator: Placebo; Participants will receive placebo to match eleclazine on Days 1 to 4.	Drug: Placebo; Placebo to match tablets administered orally in a single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Standard 12-Lead Electrocardiogram (ECG) Daytime QT Interval Corrected For Heart Rate Using The Fridericia Formula (QTcF) (AUC0-8)/8 at Day 3: Lead V5	Daytime (AUC0-8)/8 was defined as the area under the QTc curve during the 8 hours postdose, where 0 was defined as the time of dosing (i.e., T = 0) on a given day. Daytime (AUC0-8)/8 was computed by dividing AUC0-8 by the time from dosing to the 8 hour postdose time point. QTcF is corrected QT interval using Fridericia's formula.	Baseline (Day 1), Day 3
Change From Baseline in Standard 12-Lead ECG Daytime QTcF (AUC0-8)/8 at Day 3: Lead II	Daytime (AUC0-8)/8 was defined as the area under the QTc curve during the 8 hours postdose, where 0 was defined as the time of dosing (i.e.,T = 0) on a given day. Daytime (AUC0-8)/8 was computed by dividing AUC0-8 by the time from dosing to the 8 hour postdose time point. QTcF is corrected QT interval using Fridericia's formula.	Baseline (Day 1), Day 3
Change From Baseline in Standard 12-Lead ECG Daytime QTcF (AUC0-8)/8 at Day 3: Global Lead	Daytime (AUC0-8)/8 was defined as the area under the QTc curve during the 8 hours postdose, where 0 was defined as the time of dosing (i.e., T = 0) on a given day. Daytime (AUC0-8)/8 was computed by dividing AUC0-8 by the time from dosing to the 8 hour postdose time point. QTcF is corrected QT interval using Fridericia's formula.	Baseline (Day 1), Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Holter Daily QTcF Interval (Daytime and Nocturnal) at Day 3 : Lead V5	Daily Holter QTcF interval was calculated as the average of the daytime QTcF interval (AUC0-6)/6 and nocturnal QTcF interval (AUC0-6)/6. Daytime AUC0-6 was defined as the area under the QTc curve during the 6 hours postdose and nocturnal AUC0-6 was defined as the area under the QTc curve from midnight to 6am. (AUC0-6)/6 was computed by dividing AUC0-6 by the time difference over the 6 hours. QTcF is corrected QT interval using Fridericia's formula.	Baseline (Day 1), Day 3
Change From Baseline in Holter Daily QTcF Interval (Daytime and Nocturnal) at Day 3 : Global Lead	Daily Holter QTcF interval was calculated as the average of the daytime QTcF interval (AUC0-6)/6 and nocturnal QTcF interval (AUC0-6)/6. Daytime AUC0-6 was defined as the area under the QTc curve during the 6 hours postdose and nocturnal AUC0-6 was defined as the area under the QTc curve from midnight to 6am. (AUC0-6)/6 was computed by dividing AUC0-6 by the time difference over the 6 hours. QTcF is corrected QT interval using Fridericia's formula.	Baseline (Day 1), Day 3
Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Lead V5	Maximal reduction from predose (0 hour) is the maximum decrease from predose of the QTc interval (QTcF) at any time point from 1 to 8 hours postdose for Days 2 and 3. QTcF is corrected QT interval using Fridericia's formula. Predose was defined as the Day 2 predose value.	Predose, Days 2 and 3
Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Lead II	Maximal reduction from predose is the maximum decrease from predose of the QTc interval (QTcF) at any time point from 1 to 8 hours postdose for Days 2 and 3. QTcF is corrected QT interval using Fridericia's formula. Predose was defined as the Day 2 predose value.	Predose, Days 2 and 3
Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Global Lead	Maximal reduction from predose is the maximum decrease from predose of the QTc interval (QTcF) at any time point from 1 to 8 hours postdose for Days 2 and 3. QTcF is corrected QT interval using Fridericia's formula. Predose was defined as the Day 2 predose value.	Predose, Days 2 and 3

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2015
• Primary Completion (Actual): May 13, 2016
• Study Completion (Actual): June 13, 2016

Study Registration Dates

• First Submitted: February 12, 2015
• First Submitted That Met QC Criteria: February 12, 2015
• First Posted (Estimate): February 19, 2015

Study Record Updates

• Last Update Posted (Actual): December 30, 2020
• Last Update Submitted That Met QC Criteria: December 4, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Sudden Cardiac Death; LQTS; Congenital Long QT Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Syndrome; Long QT Syndrome
• Other Study ID Numbers: GS-US-394-1658

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No