A Phase I, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Inhaled CHF 6333 After Single and Repeated Ascending Doses in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
Human Neutrophil Elastase (HNE) plays a pivotal role in innate immunity and in neutrophilic lung inflammation that characterized many diseases. CHF 6333 is a potent and 24h-durable inhibitor of HNE, developed as Dry Powder Inhaler (DPI) formulation. This study is designed to investigate the tolerability, safety and pharmacokinetics of inhaled CHF6333 DPI in healthy male subjects.
The study will comprise two parts:
Part 1 will consist of two alternated cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Single Ascending Dose (SAD) of CHF6333.
Part 2 will consist of four sequential cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Multiple Ascending Dose (MAD) of CHF6333
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male subjects aged 18-55 years
- •BMI between 18-30 kg/m2
- •Non smokers
- •Lung function above 80% of predicted normal value
- •Healthy subjects based on medical evaluation including medical history, physical examination, laboratory tests and cardiac testing
排除标准
- •Any clinically relevant abnormalities and/or uncontrolled diseases
- •Abnormal laboratory values
- •Recent respiratory tract infection
- •Hypersensitivity to the drug or excipients
- •Positive serology results
- •Positive cotinine, alcohol, drug of abuse tests
- •Unsuitable veins for repeated venepuncture
研究组 & 干预措施
Placebo
干预措施: Placebo (Part 2 - MAD) (Drug)
CHF6333 Active
干预措施: CHF6333 (Part 1 - SAD) (Drug)
CHF6333 Active
干预措施: CHF6333 (Part 2 - MAD) (Drug)
Placebo
干预措施: Placebo (Part 1 - SAD) (Drug)
结局指标
主要结局
Adverse events
时间窗: Part 1 from Day 1 to 5, Part 2 from Day 1 to 15
Treatment-related Adverse events
Heart Rate
时间窗: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Change in Heart Rate (from ECG)
Clinical chemistry and haematology
时间窗: Part 1 Day 1-5, Part 2 Day 1-15
change in Clinical chemistry and haematology parameters
Urinalysis
时间窗: Part 1 Day 1-5, Part 2 Day 1-15
Change in urinalysis parameters
PR interval
时间窗: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Change in PR interval (from ECG)
Holter recording abnormalities
时间窗: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
24h-holter ECG recording
Change in Vital signs
时间窗: Part 1 from Day 1 to 5, Part 2 from Day 1 to 15
Blood pressure
QRS interval
时间窗: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Change in QRS interval (from ECG)
QTcF interval
时间窗: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Change in QTcF interval (from ECG)
FEV1
时间窗: Part 1 Day 1-2, Part 2 Day 1-14-15
Change in FEV1 (Forced exhalation volume in the first second)
次要结局
- Area under the plasma concentration(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)
- Peak plasma concentration (Cmax)(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)
- Time to reach the maximum plasma concentration (tmax)(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)
- Elimination half-life (t1/2)(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)
- Clearance (CL/F)(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)
- Volume of distribution (Vz/F)(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)
- Urinary excretion (Ae)(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)
- fraction excreted (fe)(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)
- Renal clearance (CLr)(Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15)