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

A Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Doses of CHF6297 in Healthy Subjects and Patients With COPD

Sponsors

Lead sponsor: Chiesi Farmaceutici S.p.A.

Source Chiesi Farmaceutici S.p.A.
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.

Overall Status Terminated
Start Date January 22, 2016
Completion Date March 2019
Primary Completion Date March 2019
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Secondary Outcome
Measure Time Frame
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
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
Clearance (CL/F) 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
Urinary excretion (Ae) Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
fraction excreted (fe) Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Renal clearance (CLr) Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Enrollment 118
Condition
Intervention

Intervention type: Drug

Intervention name: CHF6297 (Part 1 - SAD)

Description: Single doses of CHF6297 at each period (for up to 3 periods per subject)

Arm group label: CHF6297 Active

Intervention type: Drug

Intervention name: Placebo (Part 1 - SAD)

Description: Single doses of placebo matching CHF6297 at each period (for up to 3 periods per subject)

Arm group label: Placebo

Intervention type: Drug

Intervention name: CHF6297 (Part 2 - MAD)

Description: Twice daily doses of CHF6297 for 7 days

Arm group label: CHF6297 Active

Intervention type: Drug

Intervention name: Placebo (Part 2 - MAD)

Description: Twice daily doses of placebo matching CHF6297 for 7 days

Arm group label: Placebo

Intervention type: Drug

Intervention name: CHF6297 (Part 3)

Description: Twice daily doses of CHF6297 for 14 days

Arm group label: CHF6297 Active

Intervention type: Drug

Intervention name: Placebo (Part 3)

Description: Twice daily doses of placebo matching CHF6297 for 14 days

Arm group label: Placebo

Intervention type: Drug

Intervention name: CHF6297 (Part 4)

Description: Twice daily doses of CHF6297 for 7 days

Arm group label: CHF6297 Active

Intervention type: Drug

Intervention name: Placebo (Part 4)

Description: Twice daily doses of placebo matching CHF6297 for 7 days

Arm group label: Placebo

Eligibility

Criteria:

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

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Location
facility
Quotient Clinical
Medicines Evaluation Unit
Location Countries

United Kingdom

Verification Date

April 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: CHF6297 Active

Arm group type: Experimental

Arm group label: Placebo

Arm group type: Placebo Comparator

Acronym CHF6297 FIH
Patient Data No
Study Design Info

Allocation: Randomized

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov