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)

April 15, 2020 updated by: Chiesi Farmaceutici S.p.A.

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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

118

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Manchester, United Kingdom, M23 9QZ
        • Medicines Evaluation Unit
    • Nottingham
      • Ruddington, Nottingham, United Kingdom, NG11 6JS
        • Quotient Clinical

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Single doses of placebo matching CHF6297 at each period (for up to 3 periods per subject)
Twice daily doses of placebo matching CHF6297 for 7 days
Twice daily doses of placebo matching CHF6297 for 14 days
Twice daily doses of placebo matching CHF6297 for 7 days
EXPERIMENTAL: CHF6297 Active
Single doses of CHF6297 at each period (for up to 3 periods per subject)
Twice daily doses of CHF6297 for 7 days
Twice daily doses of CHF6297 for 14 days
Twice daily doses of CHF6297 for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Treatment-related 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
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
Blood pressure
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
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
HR, QTcF, PR, QRS + holter recording abnormalities
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
Time Frame: 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
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
Time Frame: 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
Part 1 Day 1 and Day 4, Part 2 Day 1 and Day 8, Part 3 Day 1 and Day 15

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration vs time curve
Time Frame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
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)
Time Frame: 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
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)
Time Frame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
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)
Time Frame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
Clearance (CL/F)
Time Frame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
Absolute plasma clearance
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)
Time Frame: 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
Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
Urinary excretion (Ae)
Time Frame: Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Amount of CHF6297 excreted in urine
Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
fraction excreted (fe)
Time Frame: Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Percentage of drug excreted in urine
Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Renal clearance (CLr)
Time Frame: Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 3: markers of inflammation (exploratory)
Time Frame: after 14 days of dosing
Blood and sputum biomarkers
after 14 days of dosing
Part 4: markers of inflammation (exploratory)
Time Frame: after 7 days of dosing
Blood and sputum biomarkers
after 7 days of dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 22, 2016

Primary Completion (ACTUAL)

March 1, 2019

Study Completion (ACTUAL)

March 1, 2019

Study Registration Dates

First Submitted

May 25, 2016

First Submitted That Met QC Criteria

June 23, 2016

First Posted (ESTIMATE)

June 28, 2016

Study Record Updates

Last Update Posted (ACTUAL)

April 17, 2020

Last Update Submitted That Met QC Criteria

April 15, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • CCD-06297AA1-01
  • 2015-003075-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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