A Phase 1, Study of VX-828 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
- 165
- 试验地点
- 20
- 主要终点
- Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole
研究概览
简要总结
The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics of VX-828 and VX-828 in triple combination (TC) with Tezacaftor (TEZ)/ VX-118 or TEZ/ deutivacaftor (D-IVA) in healthy participants and VX-828 in combination with D-IVA with or without TEZ in participants with cystic fibrosis (CF).
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
- 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
- •Participants between the ages of 18 and 55 years
- •Body mass index (BMI) of 18.0 to 32.0 kilogram per meter square (kg/m^2)
- •A total body weight of more than (>) 50 kg
- •Nonsmoker or ex-smoker for at least 3 months before screening with current nonsmoking status confirmed by urine or blood cotinine at screening
- •Cohort C2 only: Willing to provide a single DNA sample
- •Participants 18 years or older
- •Confirmed diagnosis of CF as determined by the investigator
- •A total body weight of more than or equal to (>=) 35 kg
- •Participants must be heterozygous for F508del with a second CFTR allele carrying a minimal function mutation that is not responsive to ELX/TEZ/IVA therapy
- •Participants must have a forced expiratory volume in 1 second (FEV1) of greater than or equal to (≥) 40% of predicted normal for age, sex, and height
排除标准
- •History of febrile illness or other acute illness within 14 days before the first dose of study drug
- •Any condition possibly affecting drug absorption
- •An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug
- •History of solid organ or hematological transplantation
- •History of clinically significant cirrhosis with or without portal hypertension
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •Other protocol defined Inclusion/Exclusion criteria will apply.
研究组 & 干预措施
Part C: Drug Drug Interaction
Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/D-IVA administration, and concomitant administration of VX-828/TEZ/D-IVA and Midazolam.
Part C will be an open-label optional cohort.
干预措施: Itraconazole (Drug)
Part D: Placebo
Participants will be randomized to receive placebo matched to VX-828/TEZ/VX-118 or placebo matched to VX-828 in combination with TEZ/D-IVA or D-IVA
干预措施: Placebo (Drug)
Part B: Placebo
Participants will be randomized to receive placebo matched to VX-828.
干预措施: Placebo (Drug)
Part A: Placebo
Participants will be randomized to receive placebo matched to VX-828.
干预措施: Placebo (Drug)
Part C: Drug Drug Interaction
Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/D-IVA administration, and concomitant administration of VX-828/TEZ/D-IVA and Midazolam.
Part C will be an open-label optional cohort.
干预措施: VX-828 (Drug)
Part C: Drug Drug Interaction
Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/D-IVA administration, and concomitant administration of VX-828/TEZ/D-IVA and Midazolam.
Part C will be an open-label optional cohort.
干预措施: Deutivacaftor (Drug)
Part C: Drug Drug Interaction
Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/D-IVA administration, and concomitant administration of VX-828/TEZ/D-IVA and Midazolam.
Part C will be an open-label optional cohort.
干预措施: Midazolam (Drug)
Part E: VX-828 in Combination with D-IVA with or without TEZ in CF
Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ.
干预措施: Deutivacaftor (Drug)
Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA
Participants will be randomized to receive VX-828 in combination with TEZ/VX-118, TEZ/D-IVA, or D-IVA.
干预措施: VX-118 (Drug)
Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA
Participants will be randomized to receive VX-828 in combination with TEZ/VX-118, TEZ/D-IVA, or D-IVA.
干预措施: VX-828 (Drug)
Part A: Single Ascending Dose (SAD)
Participants will be randomized to receive a single dose of different dose levels of VX-828.
干预措施: VX-828 (Drug)
Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA
Participants will be randomized to receive VX-828 in combination with TEZ/VX-118, TEZ/D-IVA, or D-IVA.
干预措施: Tezacaftor (Drug)
Part B: Multiple Ascending Dose (MAD)
Participants will be randomized to receive multiple doses of different dose levels of VX-828. The dose levels will be determined based on the data from Part A.
干预措施: VX-828 (Drug)
Part C: Drug Drug Interaction
Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/D-IVA administration, and concomitant administration of VX-828/TEZ/D-IVA and Midazolam.
Part C will be an open-label optional cohort.
干预措施: Tezacaftor (Drug)
Part E: VX-828 in Combination with D-IVA with or without TEZ in CF
Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ.
干预措施: Tezacaftor (Drug)
Part D: Placebo
Participants will be randomized to receive placebo matched to VX-828/TEZ/VX-118 or placebo matched to VX-828 in combination with TEZ/D-IVA or D-IVA
干预措施: Tezacaftor (Drug)
Part E: VX-828 in Combination with D-IVA with or without TEZ in CF
Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ.
干预措施: VX-828 (Drug)
Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA
Participants will be randomized to receive VX-828 in combination with TEZ/VX-118, TEZ/D-IVA, or D-IVA.
干预措施: Deutivacaftor (Drug)
Part D: Placebo
Participants will be randomized to receive placebo matched to VX-828/TEZ/VX-118 or placebo matched to VX-828 in combination with TEZ/D-IVA or D-IVA
干预措施: Deutivacaftor (Drug)
结局指标
主要结局
Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole
时间窗: From Day 1 up to Day 71
Part C: Maximum Observed Concentration (Cmax) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA
时间窗: From Day 1 up to Day 30
Part C: Area Under the Concentration Versus Time Curve (AUC) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA
时间窗: From Day 1 up to Day 30
Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 67)
Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80)
Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80)
Part C: Maximum Observed Concentration (Cmax) of VX-828 in Plasma in the Absence and Presence of Itraconazole
时间窗: From Day 1 up to Day 71
Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 67)
Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80)
Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80)
Part E: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Signing of Informed Consent Form (ICF) up to End of Study (Up to Day 111)
Part C: Maximum Observed Concentration (Cmax) of VX-828 in Plasma in the Absence and Presence of Itraconazole
时间窗: From Day 1 up to Day 71
Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole
时间窗: From Day 1 up to Day 71
Part C: Maximum Observed Concentration (Cmax) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA
时间窗: From Day 1 up to Day 30
Part C: Area Under the Concentration Versus Time Curve (AUC) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA
时间窗: From Day 1 up to Day 30
次要结局
- Part E: Pre-dose Plasma Concentration (Ctrough) of VX-828, TEZ, D-IVA and its Metabolites(Pre-dose at Day 4, Day 8, Day 15, Day 22, Day 35, Day 49, Day 63, Day 80)
- Part E: Absolute Change in Sweat Chloride(From Baseline and At Day 28)
- Part D: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma(Day 28)
- Part E: Maximum Observed Concentration (Cmax) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma(Day 1 and Day 28)
- Part E: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma(Day 28)
- Part A: Maximum Observed Concentration (Cmax) of VX-828 in Plasma(From Day 1 up to Day 67)
- Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma(From Day 1 up to Day 67)
- Part B: Maximum Observed Concentration (Cmax) of VX-828 at Day 28 in Plasma(From Day 1 up to Day 80)
- Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-828 at Day 28 in Plasma(From Day 1 up to Day 80)
- Part C: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 82))
- Part D: Maximum Observed Concentration (Cmax) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma(Day 28)