Cystic Fibrosis, Non-Cystic Fibrosis Bronchiectasis
Conditions
Brief summary
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
Interventions
DRUGCHF6333 (Part 1 - SAD)
Single doses of CHF6333 at each period
Single doses of placebo matching CHF6333 at each period
DRUGCHF6333 (Part 2 - MAD)
once daily multiple doses of CHF6333 for 14 days
once daily multiple doses of placebo matching CHF6333 for 14 days
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part 1: alternating cross-over design Part 2: parallel design
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinalysis | Part 1 Day 1-5, Part 2 Day 1-15 | Change in urinalysis parameters |
| Holter recording abnormalities | Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15 | 24h-holter ECG recording |
| FEV1 | Part 1 Day 1-2, Part 2 Day 1-14-15 | Change in FEV1 (Forced exhalation volume in the first second) |
| Adverse events | Part 1 from Day 1 to 5, Part 2 from Day 1 to 15 | Treatment-related Adverse events |
| Change in Vital signs | Part 1 from Day 1 to 5, Part 2 from Day 1 to 15 | Blood pressure |
| Heart Rate | Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15 | Change in Heart Rate (from ECG) |
| QTcF interval | Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15 | Change in QTcF interval (from ECG) |
| PR interval | Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15 | Change in PR interval (from ECG) |
| QRS interval | Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15 | Change in QRS interval (from ECG) |
| Clinical chemistry and haematology | Part 1 Day 1-5, Part 2 Day 1-15 | change in Clinical chemistry and haematology parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | maximum plasma concentration of CHF6333 |
| 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 | Absolute plasma clearance |
| Volume of distribution (Vz/F) | Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15 | plasma volume of distribution |
| Urinary excretion (Ae) | Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15 | Amount of CHF6333 excreted in urine |
| fraction excreted (fe) | Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15 | Percentage of drug excreted in urine |
| Renal clearance (CLr) | Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15 | — |
Countries
Belgium
Outcome results
None listed