- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02815488
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)
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
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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-
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Manchester, United Kingdom, M23 9QZ
- Medicines Evaluation Unit
-
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Nottingham
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Ruddington, Nottingham, United Kingdom, NG11 6JS
- Quotient Clinical
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
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Part 1 Day 1-2, Part 2 Day 1-2 and Day 7-8, Part 3 Day 1-2 and Day 14-15
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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
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Forced exhalation volume in the first second
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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
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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
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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
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Part 4: markers of inflammation (exploratory)
Time Frame: after 7 days of dosing
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Blood and sputum biomarkers
|
after 7 days of dosing
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
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)?
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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