A Phase 3, 2-Part, Open-label Study to Evaluate the Safety and Pharmacokinetics of Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 62
- 主要终点
- Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study evaluating the pharmacokinetics (PK), safety, tolerability, and pharmacodynamics (PD) of multiple doses of lumacaftor/ivacaftor (LUM/IVA) in subjects 2 through 5 years of age (inclusive) with cystic fibrosis (CF), homozygous for F508del. Subjects who participate in Part A may participate in Part B, if they meet the eligibility criteria.
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
- •Subjects who weigh ≥8 kilogram (kg) without shoes and wearing light clothing at the Screening Visit
- •Subjects with confirmed diagnosis of CF at the Screening Visit
- •Subjects who are homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation
排除标准
- •Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1
- •A standard 12-lead ECG demonstrating QTc >450 millisecond (msec) at the Screening Visit.
- •History of solid organ or hematological transplantation.
- •Ongoing or prior participation in an investigational drug study (including studies investigating LUM and/or IVA) within 30 days of the Screening Visit.
- •History of cataract/lens opacity or evidence of cataract/lens opacity determined to be clinically significant by a licensed ophthalmologist during the ophthalmologic examination at the Screening Visit
研究组 & 干预措施
Lumacaftor/Ivacaftor (LUM/IVA)
Part A (<14 kg): Participants weighing less than (<) 14 kilograms (kg) at screening received LUM 100 milligram (mg)/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A.
Part A (>=14 kg): Participants weighing greater than or equal to (>=) 14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A.
Part B (<14 kg): Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Part B (>=14 kg): Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
干预措施: LUM/IVA (Drug)
结局指标
主要结局
Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Day 1 up to Week 26
Part A: Pre-dose Concentration (Ctrough) of LUM and IVA
时间窗: Day 15
次要结局
- Part B: Absolute Change From Baseline in Stature (Height) at Week 24(Baseline, Week 24)
- Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations(Through Week 24)
- Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24(Baseline, Week 24)
- Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites(Day 15)
- Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24(Baseline, Through Week 24)
- Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Stature-for-Age Z-Score(Baseline, Week 24)
- Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Day 25)
- Part B: Absolute Change From Baseline in Weight at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Sweat Chloride at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24(Baseline, Week 24)
- Part B: Number of Pulmonary Exacerbations(Through Week 24)
- Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26(Week 24, Week 26)
- Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24(Baseline, Week 24)
- Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites(Week 24)
- Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24(Through Week 24)
- Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24(Baseline and Week 24)
- Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24(Baseline, Week 24)
- Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale(Day 1)