A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of CHF 6297 After Single and Repeated Ascending Doses in Healthy Male Subjects Followed by a Repeated Dose in COPD Patients and a 2-way, Crossover, Double-blind, Placebo-controlled, Repeated Dose Part to Investigate the Anti-inflammatory Effect of CHF 6297 After Lipopolysaccaride (LPS) Challenge in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 118
- 试验地点
- 2
- 主要终点
- Change in Laboratory parameters
研究概览
简要总结
CHF6297 is a potent and selective inhibitor of human MAP kinase p38 being developed as an anti-inflammatory agent for the treatment of inflammatory airways diseases. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of CHF6297 as dry powder formulation in healthy subjects and in COPD patients. This study is the first administration in humans.
The study will comprise four parts:
Part 1 will consist of two cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Single Ascending Dose (SAD) of CHF6297.
Part 2 will consist of four cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Multiple Ascending Dose (MAD) of CHF6297.
Part 3 will consist of one cohort of COPD patients to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of a repeat dose of CHF6297
Part 4 will consist of one cohort of healthy subjects to assess the anti-inflammatory effect of a repeat dose of CHF6297 after LPS challenge.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Parts 1,2, 4 (Healthy subjects):
- •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
- •Part 3 (COPD patients):
- •Females of childbearing potential
- •History of asthma
- •Unstable concomitant diseases
- •Abnormal relevant Holter ECG parameters
- •Recent acute exacerbations of COPD or respiratory tract infection
- •Hypersensitivity to the drug or excipients
- •Positive serology results
研究组 & 干预措施
CHF6297 Active
干预措施: CHF6297 (Part 1 - SAD) (Drug)
CHF6297 Active
干预措施: CHF6297 (Part 2 - MAD) (Drug)
CHF6297 Active
干预措施: CHF6297 (Part 3) (Drug)
CHF6297 Active
干预措施: CHF6297 (Part 4) (Drug)
Placebo
干预措施: Placebo (Part 1 - SAD) (Drug)
Placebo
干预措施: Placebo (Part 2 - MAD) (Drug)
Placebo
干预措施: Placebo (Part 3) (Drug)
Placebo
干预措施: Placebo (Part 4) (Drug)
结局指标
主要结局
Change in Laboratory parameters
时间窗: Part 1 Day 1 and Day 4, Part 2 Day 1 and Day 8, Part 3 Day 1 and Day 15
Clinical chemistry and haematology + urinalysis
Change in FEV1
时间窗: Part 1 Day 1-2, Part 2 Day 1 and Day 7-8, Part 3 Day 1, Day 10 and Day 14
Forced exhalation volume in the first second
Adverse events
时间窗: Part 1 from Day 1 until Day 4, Part 2 from Day 1 until Day 8, Part 3 from Day 1 until Day 17, Part 4 from Day 1 until Day 8
Treatment-related Adverse events
Change in Vital signs
时间窗: Part 1 from Day 1 until Day 4, Part 2 from Day 1 until Day 8, Part 3 from Day 1 until Day 17
Blood pressure
Change in Holter ECG parameters
时间窗: Part 1 Day 1-2, Part 2 Day 1-2 and Day 7-8, Part 3 Day 1-2 and Day 14-15
HR, QTcF, PR, QRS + holter recording abnormalities
次要结局
- Urinary excretion (Ae)(Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7)
- Area under the plasma concentration vs time curve(Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14)
- Elimination half-life (t1/2)(Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14)
- Clearance (CL/F)(Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14)
- fraction excreted (fe)(Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7)
- Peak plasma concentration (Cmax)(Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14)
- Time to reach the maximum plasma concentration (tmax)(Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14)
- Volume of distribution (Vz/F)(Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14)
- Renal clearance (CLr)(Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7)