Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
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.
Interventions
DRUGCHF6297 (Part 1 - SAD)
Single doses of CHF6297 at each period (for up to 3 periods per subject)
Single doses of placebo matching CHF6297 at each period (for up to 3 periods per subject)
DRUGCHF6297 (Part 2 - MAD)
Twice daily doses of CHF6297 for 7 days
Twice daily doses of placebo matching CHF6297 for 7 days
DRUGCHF6297 (Part 3)
Twice daily doses of CHF6297 for 14 days
DRUGPlacebo (Part 3)
Twice daily doses of placebo matching CHF6297 for 14 days
DRUGCHF6297 (Part 4)
Twice daily doses of CHF6297 for 7 days
DRUGPlacebo (Part 4)
Twice daily doses of placebo matching CHF6297 for 7 days
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1, Part 2, Part 4 (Healthy subjects): * Male subjects aged 18-55 years; * 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 * ability to produce an adequate induced sputum sample (study part 4 only) Part 3 (COPD patients): * Males and females aged 40-75 years * Current or past smokers * stable patients with a post-bronchodilator FEV1 between 40 and 80% of predicted normal value and FEV1/FVC ratio \<0.7 * Ability to produce a spontaneous and an adequate induced sputum sample
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Laboratory parameters | 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 | 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 | 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 | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clearance (CL/F) | Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14 | Absolute plasma clearance |
| 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 | plasma volume of distribution |
| fraction excreted (fe) | Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7 | Percentage of drug excreted in urine |
| Renal clearance (CLr) | Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7 | — |
| Urinary excretion (Ae) | Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7 | Amount of CHF6297 excreted in urine |
| 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 | — |
| 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 | maximum plasma concentration of CHF6297 |
| 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 | — |
| 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 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Part 3: markers of inflammation (exploratory) | after 14 days of dosing | Blood and sputum biomarkers |
| Part 4: markers of inflammation (exploratory) | after 7 days of dosing | Blood and sputum biomarkers |
Countries
United Kingdom
Outcome results
None listed