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

Chronic Obstructive Pulmonary Disease Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02815488
• Other study ID #: CCD-06297AA1-01
• Secondary ID: 2015-003075-30
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 22, 2016
• Est. completion date: March 2019

Study information

• Verified date: April 2020
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 118
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• CHF6297 (Part 1 - SAD)
Single doses of CHF6297 at each period (for up to 3 periods per subject)
• Placebo (Part 1 - SAD)
Single doses of placebo matching CHF6297 at each period (for up to 3 periods per subject)
• CHF6297 (Part 2 - MAD)
Twice daily doses of CHF6297 for 7 days
• Placebo (Part 2 - MAD)
Twice daily doses of placebo matching CHF6297 for 7 days
• CHF6297 (Part 3)
Twice daily doses of CHF6297 for 14 days
• Placebo (Part 3)
Twice daily doses of placebo matching CHF6297 for 14 days
• CHF6297 (Part 4)
Twice daily doses of CHF6297 for 7 days
• Placebo (Part 4)
Twice daily doses of placebo matching CHF6297 for 7 days

Locations

Country	Name	City	State
United Kingdom	Medicines Evaluation Unit	Manchester
United Kingdom	Quotient Clinical	Ruddington	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Part 3: markers of inflammation (exploratory)	Blood and sputum biomarkers	after 14 days of dosing
Other	Part 4: markers of inflammation (exploratory)	Blood and sputum biomarkers	after 7 days of dosing
Primary	Adverse events	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
Primary	Change in Vital signs	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
Primary	Change in Holter ECG parameters	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
Primary	Change in FEV1	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
Primary	Change in Laboratory parameters	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	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
Secondary	Peak plasma concentration (Cmax)	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
Secondary	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
Secondary	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
Secondary	Clearance (CL/F)	Absolute plasma clearance	Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14
Secondary	Volume of distribution (Vz/F)	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
Secondary	Urinary excretion (Ae)	Amount of CHF6297 excreted in urine	Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Secondary	fraction excreted (fe)	Percentage of drug excreted in urine	Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7
Secondary	Renal clearance (CLr)		Part 1 from Day 1 to Day 4, Part 2 Day 1 and Day 7

External Links

•   Study Record on EU Clinical Trials Register including results