A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of CHF10073 After Single and Multiple Ascending Doses in Healthy Volunteers Via Inhalation and the Effect of Multiple Doses of Itraconazole on CHF10073 Exposure
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 155
- 试验地点
- 1
- 主要终点
- Adverse events and adverse drug reactions
研究概览
简要总结
The objective of this study is to assess the safety and tolerability of single ascending doses of inhaled CHF10073 (Part 1 of the study) and multiple ascending doses of CHF10073 (Part 2 of the study). The study will also evaluate the PK profile of study drug in plasma and urine after single and repeated administrations of CHF10073.
In addition, this study will also investigate the metabolites profile of CHF10073 in plasma, urine and faeces (Part 2 of the study) and the PK profile of CHF10073 in the lungs after bronchoalveolar lavage (BAL) (Part 3 of the study).
In addition, the effect of multiple doses of itraconazole on the pharmacokinetic profile of CHF10073 will be investigated (Part 4 of the study).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- All
- 接受健康志愿者
- 是
入选标准
- •Subject's written informed consent;
- •Healthy male (Part 1 to 4) or female (Part 4) 18-55 years;
- •Understanding of the study procedures and the correct use of the inhalers;
- •BMI between 18.5 and 30.0 kg/m2;
- •Non- or ex-smokers (<5 pack-years and stopped smoking >1 year prior to screening);
- •Good physical and mental status;
- •Vital signs within normal limits; body temperature <37.5°C;
- •12-lead digitised ECG in triplicate considered as normal;
- •Lung function measurements within normal limits;
- •Males with pregnant or non-pregnant women of childbearing potential (WOCBP) partners must be willing to use contraception
- •Part 4 only: women of non-childbearing potential (WONCBP) or WOCBP with fertile male parters willing to use contraception
排除标准
- •Recent participation in another clinical trial;
- •Clinically significant abnormal 24h Holter ECG (Part 1 and 2);
- •Clinically relevant and uncontrolled medical disorders ;
- •Subjects with history of respiratory diseases ;
- •Presence of any current or recent infection;
- •Clinically relevant abnormal laboratory values;
- •Abnormal liver enzymes;
- •Positive results from the Hepatitis serology results;
- •Positive HIV-1 or HIV-2 serology results ;
- •Recent blood donation or blood loss (≥450 mL) ;
- •Heavy caffeine drinker ;
- •Recent use of any kind of electronic smoking devices;
- •Documented history of alcohol abuse within 12 months prior to screening ;
- •Documented history of drug abuse within 12 months prior to screening ;
- •Intake of non-permitted concomitant medications ;
- •Known intolerance and/or hypersensitivity to any of the study excipients ;
- •Unsuitable veins for repeated venipuncture;
- •Part 3 only: contraindication to the BAL procedure;
- •Part 3 only: recent lower respiratory tract infections
- •Part 4 only: known allergy to antifungal medicines;
- •Part 4 and females only: pregnant or lactating women
研究组 & 干预措施
CHF10073 active
干预措施: CHF10073 (Part 1 - SAD) (Drug)
CHF10073 active
干预措施: CHF10073 (Part 2 - MAD) (Drug)
CHF10073 active
干预措施: CHF10073 (Part 3) (Drug)
CHF10073 active
干预措施: CHF10073 (Part 4) (Drug)
placebo
干预措施: Placebo (Part 1 - SAD) (Drug)
placebo
干预措施: Placebo (Part 2 - MAD) (Drug)
CHF10073 + itraconazole
干预措施: itraconazole (Part 4) (Drug)
CHF10073 + itraconazole
干预措施: CHF10073 (Part 4) (Drug)
结局指标
主要结局
Adverse events and adverse drug reactions
时间窗: Through study completion, around 8 weeks in Part 1, from 10 to 13 weeks in Part 2, for about 7-8 weeks in Part 3 and for about 15 up to 17 weeks in Part 4
Vital signs (Systolic and diastolic Blood Pressure)
时间窗: From screening up to 42 days post-dose
Absolute Values for 12-lead Electrocardiogram (ECG) Recording of HR (heart rate), HR from 0 to 24 hours, hourly HR
时间窗: From screening up to 28 days post-dose
Absolute Values for 12-lead ECGs Recording of Intervals
时间窗: From screening up to 28 days post-dose
Intervals recorded: PR, QRS, QT, QTcF
Change from Baseline for Post-dose 12-lead ECGs Recording of HR, HR from 0 to 24 hours, hourly HR
时间窗: From screening up to 28 days post-dose
Change from Baseline for Post-dose 12-lead ECGs Recording of Intervals
时间窗: From screening up to 28 days post-dose
Intervals recorded: PR, QRS, QT, QTcF
Number and percentage of subjects with abnormal actual QTcF (Fridericia-corrected QT Interval).
时间窗: Part 1 and 2 only: From screening up to 28 days post-dose
Number and percentage of subjects with abnormal change from the baseline of QTcF and HR from 0 to 24 hours
时间窗: Part 1 and 2 only: From screening up to 28 days post-dose
Number of subjects and percentages by treatment with abnormal parameters derived from 24h Holter ECG recording (total pauses >2.5 secs, atrial fibrillation and atrial flutter, ventricular runs, PAC burden, PVC burden and aberrant morphologies)
时间窗: Part 1 and 2 only: From screening up to 28 days post-dose
Number of subjects with abnormal blood laboratory test results
时间窗: From screening up to 28 days post-dose
Quantitative laboratory parameters (chemistry and haematology) will be summarised by treatment as absolute value and change from baseline using descriptive statistics.
Number of subjects with abnormal urine laboratory test results
时间窗: From screening up to 28 days post-dose
Spirometry (FEV1 (Forced exhalation volume in the first second))
时间窗: From screening up to 28 days post-dose
Cough recording: average VAS (visual analogue scale))
时间窗: Part 2 only: From first dosing up to 28 days post-dose
CHF10073 plasma AUCt (Area Under the Curve from time 0 to time t)
时间窗: From first dosing up to 42 days post-dose
CHF10073 plasma Cmax (Maximum Plasma Concentration)
时间窗: From first dosing up to 42 days post-dose
Cough recording: percentage of days with cough episodes during the treatment period
时间窗: Part 2 only: From first dosing up to 28 days post-dose
次要结局
- CHF10073 plasma AUCinf (Area Under the Curve from time 0 Extrapolated to Infinity)(From first dosing up to 42 days post-dose)
- CHF10073 plasma elimination half-life(From first dosing up to 42 days post-dose)
- CHF10073 urine amount excreted (Ae)(Part 1, 2 and 4 : From first dosing up to 28 days post-dose)
- CHF10073 plasma tmax (Time to Maximum Plasma Concentration)(From first dosing up to 42 days post-dose)
- CHF10073 plasma apparent clearance (CL/F)(From first dosing up to 42 days post-dose)
- CHF10073 plasma apparent volume of distribution (Vz/F)(From first dosing up to 42 days post-dose)
- CHF10073 urine faction excreted (fe)(Part 1, 2 and 4: From first dosing up to 28 days post-dose)
- CHF10073 renal clearance (CLr)(Part 1, 2 and 4: From first dosing up to 28 days post-dose)