A Phase 1, Open-label Study to Evaluate Pharmacokinetic Drug-drug Interactions Between VX-548 and Midazolam and Digoxin in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Digoxin in the Absence and Presence of VX-548
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics of midazolam and digoxin in the absence and presence of VX-548.
详细描述
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) of 18.0 to 32.0 kilogram per meter square (Kg/m^2)
- •A total body weight greater than (>) 50 kilogram (kg)
- •Females of non-childbearing potential
排除标准
- •History of febrile illness or other acute illness that has not fully resolved within 5 days before the first dose of study drug
- •Any condition possibly affecting drug absorption
- •History of cardiovascular disease, cardiac dysrhythmias or central nervous system disease
- •Hypersensitivity to midazolam, other benzodiazepines, or digoxin
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Arm 1
Participants will receive a single dose of midazolam and digoxin on Day 1 in dosing period 1 followed by VX-548 every 12 hours (q12h) on Days 6 through 23 in dosing period 2. On Day 19, single doses of midazolam and digoxin will be administered with the morning dose of VX-548.
干预措施: VX-548 (Drug)
Arm 1
Participants will receive a single dose of midazolam and digoxin on Day 1 in dosing period 1 followed by VX-548 every 12 hours (q12h) on Days 6 through 23 in dosing period 2. On Day 19, single doses of midazolam and digoxin will be administered with the morning dose of VX-548.
干预措施: Midazolam (Drug)
Arm 1
Participants will receive a single dose of midazolam and digoxin on Day 1 in dosing period 1 followed by VX-548 every 12 hours (q12h) on Days 6 through 23 in dosing period 2. On Day 19, single doses of midazolam and digoxin will be administered with the morning dose of VX-548.
干预措施: Digoxin (Drug)
结局指标
主要结局
Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Digoxin in the Absence and Presence of VX-548
时间窗: Days 1 and 19: Pre-dose up to 120 hours post digoxin dose
Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Midazolam in the Absence and Presence of VX-548
时间窗: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
Maximum Observed Plasma Concentration (Cmax) of Digoxin in the Absence and Presence of VX-548
时间窗: Days 1 and 19: Pre-dose up to 120 hours post digoxin dose
Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Midazolam in the Absence and Presence of VX-548
时间窗: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of Digoxin in the Absence and Presence of VX-548
时间窗: Days 1 and 19: Pre-dose up to 120 hours post digoxin dose
Maximum Observed Plasma Concentration (Cmax) of Midazolam in the Absence and Presence of VX-548
时间窗: Days 1 and 19: Pre-dose up to 24 hours post midazolam dose
次要结局
- Maximum Observed Plasma Concentration (Cmax) of 1-hydroxy-Midazolam in the Absence and Presence of VX-548(Days 1 and 19: Pre-dose up to 24 hours post midazolam dose)
- Fraction of Systematically Available Digoxin Dose Excreted Unchanged (fe) in Urine in the Absence and Presence of VX-548(Days 1 and 19: Pre-dose up to 120 hours post digoxin dose)
- Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of 1-hydroxy-Midazolam in the Absence and Presence of VX-548(Days 1 and 19: Pre-dose up to 24 hours post midazolam dose)
- Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of 1-hydroxy-Midazolam in the Absence and Presence of VX-548(Days 1 and 19: Pre-dose up to 24 hours post midazolam dose)
- Renal Clearance (CLr) of Digoxin as Determined by Urine Analysis in the Absence and Presence of VX-548(Days 1 and 19: Pre-dose up to 120 hours post digoxin dose)
- Columbia-Suicide Severity Rating Scale (C-SSRS) Score(Pre-dose up to Day 39)
- Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Day 39)