A Phase 3, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age 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 A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1
研究概览
简要总结
This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of lumacaftor in combination with ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the F508del-mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
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
- 6 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of CF defined as: with 2 CF-causing mutations, chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities
- •Subjects who weigh ≥15 kg without shoes at Screening Visit
- •Subjects who are homozygous for the F508del-CFTR mutation
- •Subjects with percent predicted forced expiratory volume in 1 second (FEV1) of 70% to 105% (inclusive) (Part A) or ≥40% (Part B) at Screening Visit where the predicted values are adjusted for age, sex, and height using the Wang equation
- •Subjects with stable CF disease and who are willing to remain on stable CF medication regimen
- •Able to swallow tablets
排除标准
- •History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
- •Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1 of the study
- •Abnormal liver function as defined in the protocol at Screening Visit
- •Abnormal renal function as defined in the protocol at Screening Visit
- •History of solid organ or hematological transplantation
- •Ongoing participation in an investigational drug study or prior participation in an investigational drug study within 30 days prior of Screening Visit
- •History or evidence of lens opacity or cataract at Screening Visit
- •Colonization with organisms associated with a more rapid decline in pulmonary status at Screening Visit (Part A only)
- •A standard 12-lead ECG demonstrating QTcF >450 msec at Screening Visit
研究组 & 干预措施
Lumacaftor/Ivacaftor (LUM/IVA)
Part A Cohort 1: Participants aged 6 through 8 years will receive LUM 200 milligram (mg) in fixed-dose combination with IVA 250 mg orally every 12 hours (q12h) for 14 days.
Part A Cohort 2: Participants aged 9 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days.
Part B: Participants aged 6 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks.
干预措施: Lumacaftor (Drug)
Lumacaftor/Ivacaftor (LUM/IVA)
Part A Cohort 1: Participants aged 6 through 8 years will receive LUM 200 milligram (mg) in fixed-dose combination with IVA 250 mg orally every 12 hours (q12h) for 14 days.
Part A Cohort 2: Participants aged 9 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days.
Part B: Participants aged 6 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks.
干预措施: Ivacaftor (Drug)
结局指标
主要结局
Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1
时间窗: 4 hours post-morning dose on Day 1
Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14
时间窗: 4 hours post-morning dose on Day 14
Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA)
时间窗: Day 14 (pre-morning dose, 4, 6, 12, and 24 hours post-morning dose for LUM; pre-morning dose, 2, 4, 6, 12 hours post-morning dose for IVA)
The AUCtau is the area under the concentration versus time curve from time 0 to time tau, where tau is the time at the end of dosing interval.
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
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first study drug dose to Week 26 were considered treatment-emergent.
次要结局
- Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Day 28)
- Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4(Baseline, Day 15 and Week 4)
- Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24(Baseline, Week 24)
- Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14(Day 1, Day 14)
- Part B: Absolute Change From Baseline in BMI-for-age Z-score at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24(Baseline, 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 Body Mass Index (BMI) at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Weight at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Height at Week 24(Baseline, Week 24)
- Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24(Baseline, Week 24)
- Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA)(For Ctrough: pre-morning dose on Week 4, Week 6 and Week 24; For C3-6hr: 3 to 6 hours post-morning dose on Day 1, 15 and Week 4)
- Part B: Absolute Change From Baseline in Weight-for-age Z-score at Week 24(Baseline, Week 24)