A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in daytime QT interval corrected for heart rate using the Fridericia formula (QTcF)
研究概览
简要总结
This study will evaluate the effect of oral GS-6615 on QTc interval in healthy adults with dofetilide-induced QTc prolongation.
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 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs
- •Have a calculated body mass index (BMI) from 18 to 30 kg/m^2, inclusive, at study screening
- •Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant and which do not interfere with the ability to interpret the QT interval in the opinion of the investigator in consultation with the medical monitor
排除标准
- •History of meningitis or encephalitis, epilepsy, seizures (known or suspected), migraines, tremors, myoclonic jerks, sleep disorder, anxiety, syncope, head injuries, or a family history of seizures
- •Have any serious or active medical or psychiatric illness (including depression) which, in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment.
- •Presence or history of cardiovascular disease, including structural heart disease, myocardial infarction (by ECG and/or clinical history), history of ventricular tachycardia or torsade de pointes, heart failure or cardiomyopathy (by clinical history and/or left ventricular ejection fraction < 40%), presence of cardiac conduction abnormalities, a family history of Long QT or Brugada Syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years
- •Additional cardiovascular-specific exclusion criteria include findings on screening ECG of:
- •QTcF interval > 430 msec
- •PR interval > 220 msec
- •QRS duration > 110 msec
- •Second- or third-degree atrioventricular block
- •Complete left or right bundle branch block or incomplete right bundle branch block
- •Resting heart rate < 40 or > 100 beats per minute (bpm)
- •Pathological Q waves (defined as Q wave > 40 msec)
- •Ventricular pre-excitation
- •More than 2 ectopic beats
- •Syncope, palpitations, or unexplained dizziness
研究组 & 干预措施
Placebo to match GS-6615
Placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
干预措施: Placebo to match GS-6615 (Drug)
Placebo to match GS-6615
Placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
干预措施: Placebo to match dofetilide (Drug)
Placebo to match GS-6615
Placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
干预措施: Dofetilide (Drug)
GS-6615
GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
干预措施: GS-6615 (Drug)
GS-6615
GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
干预措施: Placebo to match GS-6615 (Drug)
GS-6615
GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
干预措施: Placebo to match dofetilide (Drug)
GS-6615
GS-6615 or placebo to match GS-6615 + dofetilide or placebo to match dofetilide twice daily
干预措施: Dofetilide (Drug)
结局指标
主要结局
Change in daytime QT interval corrected for heart rate using the Fridericia formula (QTcF)
时间窗: Up to 6 days
Pharmacokinetic (PK) profiles of GS-6615 and dofetilide
时间窗: Predose and postdose on Days -2 through Day 4
This endpoint will measure the plasma PK profiles of GS-6615 and dofetilide. PK parameters that will be measured include Cmax, Tmax, AUC_0-24, and AUC_0-tlast.
次要结局
- Incidence of adverse events, clinical laboratory test results, vital sign measurements, and electrocardiogram (ECG) data(Up to 6 days)