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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status

Terminated

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

CHF6297 (Part 1 - SAD)

Placebo (Part 1 - SAD)

CHF6297 (Part 2 - MAD)

Placebo (Part 2 - MAD)

CHF6297 (Part 3)

Placebo (Part 3)

CHF6297 (Part 4)

Placebo (Part 4)

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Quotient Clinical
Medicines Evaluation Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CHF6297 Active

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Adverse events

Treatment-related Adverse events

Change in Vital signs

Blood pressure

Change in Holter ECG parameters

HR, QTcF, PR, QRS + holter recording abnormalities

Change in FEV1

Forced exhalation volume in the first second

Change in Laboratory parameters

Clinical chemistry and haematology + urinalysis

Secondary Outcome Measures

Area under the plasma concentration vs time curve

Peak plasma concentration (Cmax)

maximum plasma concentration of CHF6297

Time to reach the maximum plasma concentration (tmax)

Elimination half-life (t1/2)

Clearance (CL/F)

Absolute plasma clearance

Volume of distribution (Vz/F)

plasma volume of distribution

Urinary excretion (Ae)

Amount of CHF6297 excreted in urine

fraction excreted (fe)

Percentage of drug excreted in urine

Renal clearance (CLr)

Full Information

NCT ID

NCT02815488

First Posted

May 25, 2016

Last Updated

April 15, 2020

Sponsor

Chiesi Farmaceutici S.p.A.

1. Study Identification

Unique Protocol Identification Number

NCT02815488

Brief Title

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

Acronym

CHF6297 FIH

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Terminated

Why Stopped

Very poor recruitment in the Part 4 of the study

Study Start Date

January 22, 2016 (Actual)

Primary Completion Date

March 2019 (Actual)

Study Completion Date

March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Chiesi Farmaceutici S.p.A.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

118 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CHF6297 Active

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

CHF6297 (Part 1 - SAD)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo (Part 1 - SAD)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

CHF6297 (Part 2 - MAD)

Intervention Description

Twice daily doses of CHF6297 for 7 days

Intervention Type

Drug

Intervention Name(s)

Placebo (Part 2 - MAD)

Intervention Description

Twice daily doses of placebo matching CHF6297 for 7 days

Intervention Type

Drug

Intervention Name(s)

CHF6297 (Part 3)

Intervention Description

Twice daily doses of CHF6297 for 14 days

Intervention Type

Drug

Intervention Name(s)

Placebo (Part 3)

Intervention Description

Twice daily doses of placebo matching CHF6297 for 14 days

Intervention Type

Drug

Intervention Name(s)

CHF6297 (Part 4)

Intervention Description

Twice daily doses of CHF6297 for 7 days

Intervention Type

Drug

Intervention Name(s)

Placebo (Part 4)

Intervention Description

Twice daily doses of placebo matching CHF6297 for 7 days

Primary Outcome Measure Information:

Title

Adverse events

Description

Treatment-related Adverse events

Time Frame

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

Title

Change in Vital signs

Description

Blood pressure

Time Frame

Part 1 from Day 1 until Day 4, Part 2 from Day 1 until Day 8, Part 3 from Day 1 until Day 17

Title

Change in Holter ECG parameters

Description

HR, QTcF, PR, QRS + holter recording abnormalities

Time Frame

Part 1 Day 1-2, Part 2 Day 1-2 and Day 7-8, Part 3 Day 1-2 and Day 14-15

Title

Change in FEV1

Description

Forced exhalation volume in the first second

Time Frame

Part 1 Day 1-2, Part 2 Day 1 and Day 7-8, Part 3 Day 1, Day 10 and Day 14

Title

Change in Laboratory parameters

Description

Clinical chemistry and haematology + urinalysis

Time Frame

Part 1 Day 1 and Day 4, Part 2 Day 1 and Day 8, Part 3 Day 1 and Day 15

Secondary Outcome Measure Information:

Title

Area under the plasma concentration vs time curve

Time Frame