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

Phase 1

Completed

Conditions: LQT2 Syndrome

Interventions: Drug: Eleclazine
Drug: Placebo

Registration Number: NCT02365506

Lead Sponsor: Gilead Sciences

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Eleclazine 48 mg + Placebo	Placebo	Participants will receive placebo to match eleclazine on Days 1, 2 and 4, and eleclazine 48 mg on Day 3.
Placebo	Placebo	Participants will receive placebo to match eleclazine on Days 1 to 4.
Eleclazine 24 mg + Eleclazine 48 mg + Placebo	Eleclazine	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.
Eleclazine 24 mg + Eleclazine 48 mg + Placebo	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.
Eleclazine 48 mg + Placebo	Eleclazine	Participants will receive placebo to match eleclazine on Days 1, 2 and 4, and eleclazine 48 mg on Day 3.

Primary Outcome Measures

Name	Time	Method
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	Baseline (Day 1), Day 3	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.
Change From Baseline in Standard 12-Lead ECG Daytime QTcF (AUC0-8)/8 at Day 3: Global Lead	Baseline (Day 1), Day 3	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.
Change From Baseline in Standard 12-Lead ECG Daytime QTcF (AUC0-8)/8 at Day 3: Lead II	Baseline (Day 1), Day 3	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.

Secondary Outcome Measures

Name	Time	Method
Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Lead II	Predose, Days 2 and 3	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.
Change From Baseline in Holter Daily QTcF Interval (Daytime and Nocturnal) at Day 3 : Global Lead	Baseline (Day 1), Day 3	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.
Change From Baseline in Holter Daily QTcF Interval (Daytime and Nocturnal) at Day 3 : Lead V5	Baseline (Day 1), Day 3	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.
Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Lead V5	Predose, Days 2 and 3	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.
Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Global Lead	Predose, Days 2 and 3	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.