A Double-blind, Placebo-controlled Study to Evaluate the Effect of GS-6615 on QT, Safety and Tolerability in Subjects With Long QT2 Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Placebo
Participants will receive placebo to match eleclazine on Days 1 to 4.
干预措施: Placebo (Drug)
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.
干预措施: Eleclazine (Drug)
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.
干预措施: Placebo (Drug)
Eleclazine 48 mg + Placebo
Participants will receive placebo to match eleclazine on Days 1, 2 and 4, and eleclazine 48 mg on Day 3.
干预措施: Eleclazine (Drug)
Eleclazine 48 mg + Placebo
Participants will receive placebo to match eleclazine on Days 1, 2 and 4, and eleclazine 48 mg on Day 3.
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Lead II(Predose, Days 2 and 3)
- Change From Baseline in Holter Daily QTcF Interval (Daytime and Nocturnal) at Day 3 : Global Lead(Baseline (Day 1), Day 3)
- Change From Baseline in Holter Daily QTcF Interval (Daytime and Nocturnal) at Day 3 : Lead V5(Baseline (Day 1), Day 3)
- Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Lead V5(Predose, Days 2 and 3)
- Maximum Reduction From Predose in Standard 12-Lead QTcF on Days 2 and 3: Global Lead(Predose, Days 2 and 3)