A Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Evaluate Safety, Pharmacokinetics (PK) and Pharmacodynamics(PD) of FDL169 in Cystic Fibrosis (CF) Subjects Homozygous for the F508del-CFTR Mutation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 13
- 主要终点
- Incidence of Treatment-Emergent Adverse Events
研究概览
简要总结
This is a multicenter, randomized, placebo-controlled, dose-escalation study. Enrollment is planned to occur at approximately 14 global sites. Approximately 24 subjects with CF.
详细描述
This is a multicenter, randomized double-blind, placebo-controlled dose-escalation and parallel-arm, dose-ranging study. Enrollment is planned to occur at approximately 14 global sites. Approximately 24 subjects with CF who are homozygous for the F508del-CFTR mutation will be enrolled in two cohorts.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects with a confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis or two CF-causing mutations,documented in the subject's medical record or confirmed at screening.
- •Age 18 and above on the date of informed consent.
- •Weight ≥40 kg.
- •Homozygous for the F508del-CFTR mutation. Genotyping to be confirmed at screening.
- •Ability to perform a valid, reproducible spirometry test with demonstration of a forced expiratory volume in 1 sec (FEV1) >40% of predicted normal for age, sex and height.
- •Screening laboratory tests with no clinically significant abnormalities that would interfere with the study assessments (as judged by the Investigator).
- •Subjects who are sexually active must agree to follow the study's contraception requirements.
排除标准
- •An acute upper or lower respiratory tract infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks prior to Day
- •Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening.
- •Impaired renal function or known portal hypertension.
- •History of prolonged QT and/or QTcF (Fridericia's correction) interval (>450 msec) or QTcF >450 msec at Screening.
- •History of solid organ or hematological transplantation.
- •History of alcohol abuse or drug addiction (including cannabis, cocaine and opiates) during the past year, (as judged by the Investigator).
- •Use of ivacaftor or lumacaftor, within 4 weeks of Day 1
- •Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to Day
- •Ongoing immunosuppressive therapy (including systemic corticosteroids).
- •Hemoglobin <10 g/dL.
- •Abnormal liver function, at screening.
- •Abnormal renal function at screening.
- •Ongoing participation in another clinical study or prior participation without appropriate washout (minimum of 10 half- lives or 30 days, whichever is longer) prior to Screening visit.
研究组 & 干预措施
FDL 169 test formulation (Dose Level 1)
Multiple dose (Dose Level 1) FDL 169 test formulation administered as repeat doses in CF subjects
干预措施: FDL169 (Drug)
FDL 169 test formulation (Dose Level 2)
Multiple dose (Dose Level 2) FDL 169 test formulation administered as repeat doses in CF subjects
干预措施: FDL169 (Drug)
FDL 169 test formulation ( Dose Level 3)
Multiple dose (Dose Level 3) FDL 169 test formulation administered as repeat doses in CF subjects
干预措施: FDL169 (Drug)
Placebo
Multiple dose placebo as repeat doses in CF subjects
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events
时间窗: 28 days
Safety and tolerability of FDL169 as determined by the incidence of adverse events (AEs) and serious adverse events (SAEs).
次要结局
- Pharmacokinetic parameters, Cmax(28 days)
- Pharmacokinetic parameters, AUC(28 days)
- Pharmacokinetic parameters, CL/F(28 days)
- Pharmacokinetic parameters, Tmax(28 days)
- Pharmacokinetic parameters, V/F(28 days)