A Phase 1, Open-label Study to Evaluate the Pharmacokinetics and Safety of Multiple Doses of VX-548 in Subjects With Mild or Moderate Hepatic Impairment and in Matched Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of VX-548
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics and safety of multiple doses of VX-584 in participants with mild or moderate hepatic impairment as compared to matched healthy controls.
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
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Cohorts 1 and 3: Participants with Mild or Moderate Hepatic Impairment
- •Participants will satisfy the criteria for mild (Cohort 1) and moderate hepatic impairment (Cohort 3) defined as a Child-Pugh total score of 5 to 6 and 7 to 9 points, respectively at the screening visit
- •Participants will have chronic (greater than or equal to (≥) 6 months) documented liver disease
- •Cohorts 2 and 4: Matched Healthy Participants
- •Participants will be matched (cohort 2 matched to cohort 1; and cohort 4 matched to cohort 3) during screening to participants with hepatic impairment for age, sex, and weight
排除标准
- •Cohorts 1 and 3: Participants with Mild or Moderate Hepatic Impairment
- •History of febrile illness or other acute illness that has not fully resolved by 14 days before the first dose of study drug
- •Severe portal hypertension
- •History or presence of severe hepatic encephalopathy (Grade >2)
- •Any condition possibly affecting drug absorption
- •Significant renal dysfunction (creatinine clearance <60 milliliter per minute [mL/min] ) estimated according to the method of Cockcroft and Gault at the screening Visit or Day-1
- •History of solid organ or bone marrow transplantation
- •Cohorts 2 and 4: Matched Healthy Participants
- •History of febrile illness or other acute illness that has not fully resolved by 14 days before the first dose of study drug
- •Any condition possibly affecting drug absorption
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1: Mild Hepatic Impairment
Participants will receive multiple doses of VX-548 every 12 hours (q12h) from Day 1 through Day 14.
干预措施: VX-548 (Drug)
Cohort 2: Matched Healthy Participants
Healthy participants matched to cohort 1 will receive multiple doses of VX-548 q12h from Day 1 through Day 14.
干预措施: VX-548 (Drug)
Cohort 3: Moderate Hepatic Impairment
Participants will receive multiple doses of VX-548 q12h from Day 1 through Day 14.
干预措施: VX-548 (Drug)
Cohort 4: Matched Healthy Participants
Healthy participants matched to cohort 3 will receive multiple doses of VX-548 q12h from Day 1 through Day 14.
干预措施: VX-548 (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of VX-548
时间窗: Day 1 to Day 31
Area Under the Plasma Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548
时间窗: Day 1 to Day 31
Apparent Volume of Distribution of VX-548 (Vz/F)
时间窗: Day 1 to Day 31
Time Required for Plasma Concentration of VX-548 to Reduce to Half (t1/2)
时间窗: Day 1 to Day 31
Time Taken for VX-548 to Reach Maximum Concentration (tmax)
时间窗: Day 1 to Day 31
Apparent Clearance of VX-548 (CL/F)
时间窗: Day 1 to Day 31
Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to the Last Measured Concentration (AUC0-last) of VX-548
时间窗: Day 1 to Day 31
次要结局
- Maximum Observed Plasma Concentration (Cmax) of VX-548 Metabolite(Day 1 to Day 31)
- Apparent Clearance of VX-548 Metabolite (CL/F)(Day 1 to Day 31)
- Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to the Last Measured Concentration (AUC0-last) of VX-548 Metabolite(Day 1 to Day 31)
- Area Under the Plasma Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548 Metabolite(Day 1 to Day 31)
- Apparent Volume of Distribution of VX-548 Metabolite (Vz/F)(Day 1 to Day 31)
- Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Day 1 up to Day 42)
- Time Taken for VX-548 metabolite to Reach Maximum Concentration (tmax)(Day 1 to Day 31)
- Time Required for Plasma Concentration of VX-548 Metabolite to Reduce to Half (t1/2)(Day 1 to Day 31)
- Fraction Unbound (fu) for VX-548 and its Metabolite in Plasma(Day 14: Up to 24 hours Post-dose)
- Unbound Area Under the Concentration Versus Time Curve of VX-548 and its Metabolite(Day 14: Up to 24 hours Post-dose)