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
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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2016-06-28
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Adverse events
timeFrame: 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
measure: Change in Vital signs
timeFrame: Part 1 from Day 1 until Day 4, Part 2 from Day 1 until Day 8, Part 3 from Day 1 until Day 17
measure: Change in Holter ECG parameters
timeFrame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 7-8, Part 3 Day 1-2 and Day 14-15
measure: Change in FEV1
timeFrame: Part 1 Day 1-2, Part 2 Day 1 and Day 7-8, Part 3 Day 1, Day 10 and Day 14
measure: Change in Laboratory parameters
timeFrame: Part 1 Day 1 and Day 4, Part 2 Day 1 and Day 8, Part 3 Day 1 and Day 15
Secondary outcomes:
measure: Area under the plasma concentration vs time curve
timeFrame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
measure: Peak plasma concentration (Cmax)
timeFrame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
measure: Time to reach the maximum plasma concentration (tmax)
timeFrame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
measure: Elimination half-life (t1/2)
timeFrame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
measure: Clearance (CL/F)
timeFrame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
measure: Volume of distribution (Vz/F)
timeFrame: Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
measure: Urinary excretion (Ae)
timeFrame: Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
measure: fraction excreted (fe)
timeFrame: Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
measure: Renal clearance (CLr)
timeFrame: Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Other outcomes:
measure: Part 3: markers of inflammation (exploratory)
timeFrame: after 14 days of dosing
measure: Part 4: markers of inflammation (exploratory)
timeFrame: after 7 days of dosing
Locations:
city: Ruddington
country: United Kingdom
facility: Quotient Clinical
state: Nottingham
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
affiliation: Quotient Clinical
name: Stuart Mair, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medicines Evaluation Unit
name: Dave Singh, MD
role: PRINCIPAL_INVESTIGATOR
References: