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

Sponsor
Chiesi Farmaceutici S.p.A. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02815488
Collaborator
(none)
118
Enrollment
2
Locations
2
Arms
37.3
Actual Duration (Months)
59
Patients Per Site
1.6
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: CHF6297 (Part 1 - SAD)
  • Drug: Placebo (Part 1 - SAD)
  • Drug: CHF6297 (Part 2 - MAD)
  • Drug: Placebo (Part 2 - MAD)
  • Drug: CHF6297 (Part 3)
  • Drug: Placebo (Part 3)
  • Drug: CHF6297 (Part 4)
  • Drug: Placebo (Part 4)
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
118 participants
Allocation:
Randomized
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 22, 2016
Actual Primary Completion Date :
Mar 1, 2019
Actual Study Completion Date :
Mar 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: CHF6297 Active

Drug: CHF6297 (Part 1 - SAD)
Single doses of CHF6297 at each period (for up to 3 periods per subject)

Drug: CHF6297 (Part 2 - MAD)
Twice daily doses of CHF6297 for 7 days

Drug: CHF6297 (Part 3)
Twice daily doses of CHF6297 for 14 days

Drug: CHF6297 (Part 4)
Twice daily doses of CHF6297 for 7 days
Placebo Comparator: Placebo

Drug: Placebo (Part 1 - SAD)
Single doses of placebo matching CHF6297 at each period (for up to 3 periods per subject)

Drug: Placebo (Part 2 - MAD)
Twice daily doses of placebo matching CHF6297 for 7 days

Drug: Placebo (Part 3)
Twice daily doses of placebo matching CHF6297 for 14 days

Drug: Placebo (Part 4)
Twice daily doses of placebo matching CHF6297 for 7 days

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

Secondary Outcome Measures

  1. 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]

  2. 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

  3. 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]

  4. 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]

  5. 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

  6. 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

  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

  8. fraction excreted (fe) [Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7]

    Percentage of drug excreted in urine

  9. Renal clearance (CLr) [Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7]

Other Outcome Measures

  1. Part 3: markers of inflammation (exploratory) [after 14 days of dosing]

    Blood and sputum biomarkers

  2. Part 4: markers of inflammation (exploratory) [after 7 days of dosing]

    Blood and sputum biomarkers

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Quotient Clinical Ruddington Nottingham United Kingdom NG11 6JS
2 Medicines Evaluation Unit Manchester United Kingdom M23 9QZ

Sponsors and Collaborators

  • Chiesi Farmaceutici S.p.A.

Investigators

  • Principal Investigator: Stuart Mair, MD, Quotient Clinical
  • Principal Investigator: Dave Singh, MD, Medicines Evaluation Unit

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier:
NCT02815488
Other Study ID Numbers:
  • CCD-06297AA1-01
  • 2015-003075-30
First Posted:
Jun 28, 2016
Last Update Posted:
Apr 17, 2020
Last Verified:
Apr 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Additional relevant MeSH terms:
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive

Study Results

No Results Posted as of Apr 17, 2020