Pulmonary Fibrosis
Conditions
Brief summary
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).
Interventions
DRUGCHF10073 (Part 1 - SAD)
Single doses of CHF10073 for each cohort
Single doses of placebo matching CHF10073 for each cohort
DRUGCHF10073 (Part 2 - MAD)
Multiple doses of CHF10073 for each cohort
DRUGCHF10073 (Part 3)
Single dose of CHF10073
Multiple doses of placebo matching CHF10073 for each cohort
DRUGitraconazole (Part 4)
Multiple dose of itraconazole in treatment period 2
DRUGCHF10073 (Part 4)
Single dose of CHF10073 in Treatment Period 1 and 2
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part 1 - SAD (single ascending dose): Randomised, double-blind, placebo-controlled, single-dose escalation, parallel-group design in HVs. Part 2 - MAD (multiple ascending dose): Randomised, double-blind, placebo-controlled, repeated-dose escalation, parallel-group design in HVs; Part 3: Non-randomised, open-label, single dose design in HVs Part 4 - Non-randomised, open-label, one-sequence, two-period crossover design in HVs.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events and adverse drug reactions | 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) | 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 | From screening up to 28 days post-dose | — |
| Absolute Values for 12-lead ECGs Recording of Intervals | 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 | From screening up to 28 days post-dose | — |
| Change from Baseline for Post-dose 12-lead ECGs Recording of Intervals | 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). | 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 | 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) | Part 1 and 2 only: From screening up to 28 days post-dose | — |
| Number of subjects with abnormal blood laboratory test results | 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 | From screening up to 28 days post-dose | — |
| Spirometry (FEV1 (Forced exhalation volume in the first second)) | From screening up to 28 days post-dose | — |
| Cough recording: percentage of days with cough episodes during the treatment period | Part 2 only: From first dosing up to 28 days post-dose | — |
| Cough recording: average VAS (visual analogue scale)) | 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) | From first dosing up to 42 days post-dose | — |
| CHF10073 plasma Cmax (Maximum Plasma Concentration) | From first dosing up to 42 days post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| CHF10073 plasma AUCinf (Area Under the Curve from time 0 Extrapolated to Infinity) | From first dosing up to 42 days post-dose |
| CHF10073 plasma tmax (Time to Maximum Plasma Concentration) | From first dosing up to 42 days post-dose |
| CHF10073 plasma elimination half-life | 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 amount excreted (Ae) | Part 1, 2 and 4 : From first dosing up to 28 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 |
Countries
Belgium
Contacts
PRINCIPAL_INVESTIGATORJelle Klein, MD
SGS Belgium
Outcome results
None listed