A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 35
- 主要终点
- Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5 years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at least 1 allele.
Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through 5 years of age.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female with confirmed diagnosis of CF
- •Must have a CFTR gating mutation in at least 1 allele
- •Aged 2 through 5 years at screening and Day 1
- •Weight >= 8 kg at screening and Day 1
- •Hematology, serum chemistry, coagulation, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator
排除标准
- •History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant
- •An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks before Day 1
- •Abnormal liver function, at screening
- •History of solid organ or hematological transplantation
- •Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1
- •Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives before screening
研究组 & 干预措施
Ivacaftor
Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than [<] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [>=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study..
Part B: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study.
干预措施: Ivacaftor (Drug)
结局指标
主要结局
Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
时间窗: Part A: Up to 93 Days
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
Part A: Plasma Concentration of Ivacaftor and Its Metabolites
时间窗: Part A: up to 24 hours post-dose on Day 4
Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor \[M1\] and ivacaftor carboxylate \[M6\]) up to 24 hours post-dose on Day 4 (Hour 0 \[pre-dose\] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
时间窗: Part B: Up to 28 Weeks
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.
次要结局
- Part B: Absolute Change From Baseline in Sweat Chloride at Week 24(Part B: Baseline, Week 24)
- Part B: Absolute Change From Baseline in Stature at Week 24(Part B: Baseline, Week 24)
- Part B: Absolute Change From Baseline in Weight at Week 24(Part B: Baseline, Week 24)
- Part B: Plasma Concentration of Ivacaftor and Its Metabolites(Part B: up to 24 hours post-dose on Day 168)
- Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24(Baseline, Week 24)