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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 12
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Eleclazine (Single-blind treatment phase)
Eleclazine and/or eleclazine placebo up to Week 24
干预措施: Eleclazine (Drug)
Eleclazine (Single-blind treatment phase)
Eleclazine and/or eleclazine placebo up to Week 24
干预措施: Eleclazine placebo (Drug)
Open-label Extension Phase
Eligible participants will continue to receive open-label eleclazine until this drug is commercially available for the treatment of patients with LQT3, or until Gilead terminates development of eleclazine for the treatment of patients with LQT3, or the investigator deems it no longer in the participant's best interest.
干预措施: Eleclazine (Drug)
结局指标
主要结局
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)
时间窗: Baseline; Week 24
* 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.
次要结局
- Change From Baseline in Mean Daytime QTcF Interval (AUC0-6/6) to Week 12 (Lead V5; Standard 12-lead ECG)(Baseline; Week 12)
- Change From Baseline in Mean Daily (Daytime and Nocturnal) QTcF Interval to Week 24 (Lead V5; Holter)(Baseline; Week 24)
- Change From Baseline in Mean Nocturnal QTcF Interval to Week 24 (Lead V5; Holter)(Baseline; Week 24)