A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of VX-809 to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of VX-809 in Cystic Fibrosis Subjects Homozygous for the ∆F508-CFTR Gene Mutation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 93
- 主要终点
- Safety and Tolerability Based on Adverse Events (AEs)
研究概览
简要总结
The primary objective of the study was to evaluate the safety and tolerability of VX-809 in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
详细描述
This was a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose study of orally-administered VX-809 in participants with CF who are homozygous for the specific CFTR mutation known as ∆F508 or F508del. Enrollment was planned for 90 participants at approximately 20 centers. Participants were planned to be randomized in a 4:1 ratio to receive 1 of 4 doses of VX-809 or placebo once a day for 28 days in a parallel design. Participants were outpatients during the study, except for overnight stays on Day 1 and 28.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of CF with ∆F508-CFTR mutation in both alleles
- •Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) of predicted normal for age, gender, and height
- •Weight >=40 kilograms (kg) and body mass index greater than or equal to 18.5 kilogram per square meter (kg/m^2)
- •Screening laboratory values, tests, and physical examination within acceptable ranges
- •Negative pregnancy test (for women of child-bearing potential)
- •Able and willing to follow contraceptive requirements
- •Willing to remain on a stable medication regimen for the duration of study participation
排除标准
- •History of any illness, or any ongoing acute illness, that could impact the safety of the study participant or may confound results of study
- •Pulmonary exacerbation or changes in therapy for pulmonary disease within 14 days before receiving the first dose of study drug
- •Impaired hepatic or renal function
- •History of organ or hematological transplant
研究组 & 干预措施
Placebo
Placebo matched to VX-809 capsule orally once daily for 28 days.
干预措施: Placebo (Drug)
VX-809, 25 mg
VX-809, 25 milligram (mg) capsule orally once daily for 28 days.
干预措施: VX-809 (Drug)
VX-809, 50 mg
VX-809, 50 mg capsule orally once daily for 28 days.
干预措施: VX-809 (Drug)
VX-809, 100 mg
VX-809, 100 mg capsule orally once daily for 28 days.
干预措施: VX-809 (Drug)
VX-809, 200 mg
VX-809, 200 mg capsule orally once daily for 28 days.
干预措施: VX-809 (Drug)
结局指标
主要结局
Safety and Tolerability Based on Adverse Events (AEs)
时间窗: Up to 14 days after last dose (last dose = Day 28)
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. Serious adverse event (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, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.
次要结局
- Change From Baseline in Sweat Chloride at Day 28(Baseline, Day 28)
- Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28(Baseline, Day 28)
- Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28(Baseline, Day 28)
- Maximum Plasma Concentration (Cmax) of VX-809(Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose))
- Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809(Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose))
- Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28(Baseline, Day 28)
- Change From Baseline in Percent Predicted FEV1 at Day 28(Baseline, Day 28)
- Change From Baseline in Forced Vital Capacity (FVC) at Day 28(Baseline, Day 28)
- Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28(Baseline, Day 28)