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

Phase 1

Terminated

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: CHF6297 (Part 1 - SAD); Drug: Placebo (Part 1 - SAD); Drug: CHF6297 (Part 2 - MAD); Drug: Placebo (Part 2 - MAD); Drug: Placebo (Part 3); Drug: CHF6297 (Part 3); Drug: CHF6297 (Part 4); Drug: Placebo (Part 4)

• Registration Number: NCT02815488
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01-22
• Study First Submitted: 2016-05-25
• Study First Submitted QC: 2016-06-23
• Study First Posted: 2016-06-28
• Primary Completion: 2019-03
• Study Completion: 2019-03
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-15
• Last Update Posted: 2020-04-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 118

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CHF6297 Active	CHF6297 (Part 1 - SAD)	-
Placebo	Placebo (Part 3)	-
CHF6297 Active	CHF6297 (Part 2 - MAD)	-
CHF6297 Active	CHF6297 (Part 3)	-
CHF6297 Active	CHF6297 (Part 4)	-
Placebo	Placebo (Part 1 - SAD)	-
Placebo	Placebo (Part 2 - MAD)	-
Placebo	Placebo (Part 4)	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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	Absolute plasma clearance
fraction excreted (fe)	Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7	Percentage of drug excreted in urine
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
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
Renal clearance (CLr)	Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7

Trial Locations

Locations (2)

Quotient Clinical; 🇬🇧 Ruddington, Nottingham, United Kingdom

Medicines Evaluation Unit; 🇬🇧 Manchester, United Kingdom