A Phase 1/2 Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 7
- 主要终点
- Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate safety and tolerability of VX-121 in healthy subjects and in subjects with cystic fibrosis (CF).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part A, B, and C: Healthy Volunteers
- •Female subjects must be of non-childbearing potential
- •Between the ages of 18 and 55 years, inclusive
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg
- •Part D: Subjects with CF
- •Heterozygous for F508del and an MF mutation (F/MF)
- •FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height
- •Body weight ≥35 kg
排除标准
- •Part A, B and C: Healthy Volunteers
- •Any condition possibly affecting drug absorption
- •History of febrile illness or other acute illness within 5 days before the first study drug dose
- •Part D: Subjects with CF
- •History of clinically significant cirrhosis with or without portal hypertension
- •History of solid organ or hematological transplantation
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Part A: Pooled Placebo (Cohorts A1-5; Except A3)
Participants received single dose of placebo matched to VX-121.
干预措施: Placebo (matched to VX-121 suspension) (Drug)
Part A: VX-121 (Cohort A1)
Participants received single dose of VX-121 10 milligrams (mg).
干预措施: VX-121 (Suspension) (Drug)
Part A: VX-121 (Cohort A2)
Participants received single dose of VX-121 20 mg.
干预措施: VX-121 (Suspension) (Drug)
Part A: VX-121 (Cohort A3)
Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.
干预措施: Placebo (matched to VX-121 suspension) (Drug)
Part C: Pooled Placebo (Cohorts C1-3)
Participants received placebo matched to VX-121/TEZ/IVA for 14 days.
干预措施: Placebo (matched to VX-121 suspension) (Drug)
Part A: VX-121 (Cohort A3)
Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.
干预措施: VX-121 (Suspension) (Drug)
Part A: VX-121 (Cohort A4)
Participants received single dose of VX-121 40 mg.
干预措施: VX-121 (Suspension) (Drug)
Part A: VX-121 (Cohort A5)
Participants received single dose of VX-121 60 mg.
干预措施: VX-121 (Suspension) (Drug)
Part A: VX-121 (Cohort A9)
Participants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17.
干预措施: VX-121 (Suspension) (Drug)
Part A: VX-121 (Cohort A9)
Participants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17.
干预措施: VX-121 (Tablet) (Drug)
Part B: Pooled Placebo (Cohorts B1-4)
Participants received placebo matched to VX-121 for 10 days.
干预措施: Placebo (matched to VX-121 suspension) (Drug)
Part B: VX-121 (Cohort B1)
Participants received VX-121 10 mg once daily (qd) for 10 days.
干预措施: VX-121 (Suspension) (Drug)
Part B: VX-121 (Cohort B2)
Participants received VX-121 20 mg qd for 10 days.
干预措施: VX-121 (Suspension) (Drug)
Part B: VX-121 (Cohort B3)
Participants received VX-121 40 mg qd for 10 days.
干预措施: VX-121 (Suspension) (Drug)
Part B: VX-121 (Cohort B4)
Participants received VX-121 60 mg qd for 10 days.
干预措施: VX-121 (Suspension) (Drug)
Part C: Pooled Placebo (Cohorts C1-3)
Participants received placebo matched to VX-121/TEZ/IVA for 14 days.
干预措施: Placebo (matched to TEZ/IVA) (Drug)
Part C: Pooled Placebo (Cohorts C1-3)
Participants received placebo matched to VX-121/TEZ/IVA for 14 days.
干预措施: Placebo (matched to IVA) (Drug)
Part C: VX-121 (Cohort C1)
Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.
干预措施: VX-121 (Suspension) (Drug)
Part C: VX-121 (Cohort C1)
Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.
干预措施: TEZ/IVA (Drug)
Part C: VX-121 (Cohort C1)
Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.
干预措施: IVA (Drug)
Part C: VX-121 (Cohort C2)
Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
干预措施: VX-121 (Suspension) (Drug)
Part C: VX-121 (Cohort C2)
Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
干预措施: TEZ/IVA (Drug)
Part C: VX-121 (Cohort C2)
Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
干预措施: IVA (Drug)
Part C: VX-121 (Cohort C3)
Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
干预措施: VX-121 (Suspension) (Drug)
Part C: VX-121 (Cohort C3)
Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
干预措施: TEZ/IVA (Drug)
Part C: VX-121 (Cohort C3)
Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
干预措施: IVA (Drug)
Part D: Placebo
Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.
干预措施: Placebo (matched to TEZ/IVA) (Drug)
Part D: Placebo
Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.
干预措施: Placebo (matched to IVA) (Drug)
Part D: Placebo
Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.
干预措施: Placebo (matched to VX-121 tablet) (Drug)
Part D: VX-121/TEZ/IVA
Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.
干预措施: TEZ/IVA (Drug)
Part D: VX-121/TEZ/IVA
Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.
干预措施: IVA (Drug)
Part D: VX-121/TEZ/IVA
Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.
干预措施: VX-121 (Tablet) (Drug)
结局指标
主要结局
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: From Day 1 Through Safety Follow-up (up to Day 15 for Part A [except Cohorts A3 and A9], up to Day 26 for Cohort A3, up to Day 34 for Cohort A9, up to Day 20 for Part B, up to Day 24 for Part C and up to Week 9 for Part D)
次要结局
- Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)(Day 1 and Day 15)
- Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(From Baseline Through Day 29)
- Part B: Maximum Observed Concentration (Cmax) of VX-121(Day 1, Day 5, and Day 10)
- Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)(Pre-dose at Day 7 and Day 14)
- Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA)(Day 1, Day 7, and Day 14)
- Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)(Day 1 and Day 15)
- Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121(Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose)
- Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121(Pre-dose at Day 5 and Day 10)
- Part A: Maximum Observed Concentration (Cmax) of VX-121(Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose)
- Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121(Day 1, Day 5, and Day 10)
- Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)(Day 1, Day 7, and Day 14)
- Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)(Pre-dose at Day 8, Day 15, and Day 29)
- Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations(From Baseline Through Day 29)