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

NCT02815488 | Terminated Phase 1

• 2 other identifiers: CCD-06297AA1-012015-003075-30
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (9)

• 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

• 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

• 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

• 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

• Clearance (CL/F)

  Part 1 Day 1 until Day 4, Part 2 Day 1 and Day 7, Part 3 Day 1 and Day 14

Other Outcomes (2)

• Part 3: markers of inflammation (exploratory)

  after 14 days of dosing

• Part 4: markers of inflammation (exploratory)

  after 7 days of dosing

Study Arms (2)

CHF6297 Active

EXPERIMENTAL

Drug: CHF6297 (Part 1 - SAD); Drug: CHF6297 (Part 2 - MAD); Drug: CHF6297 (Part 3); Drug: CHF6297 (Part 4)

Placebo

PLACEBO COMPARATOR

Drug: Placebo (Part 1 - SAD); Drug: Placebo (Part 2 - MAD); Drug: Placebo (Part 3); Drug: Placebo (Part 4)

Interventions

CHF6297 (Part 1 - SAD) DRUG

Single doses of CHF6297 at each period (for up to 3 periods per subject)

CHF6297 Active

Placebo (Part 1 - SAD) DRUG

Single doses of placebo matching CHF6297 at each period (for up to 3 periods per subject)

Placebo

CHF6297 (Part 2 - MAD) DRUG

Twice daily doses of CHF6297 for 7 days

CHF6297 Active

Placebo (Part 2 - MAD) DRUG

Twice daily doses of placebo matching CHF6297 for 7 days

Placebo

CHF6297 (Part 3) DRUG

Twice daily doses of CHF6297 for 14 days

CHF6297 Active

Placebo (Part 3) DRUG

Twice daily doses of placebo matching CHF6297 for 14 days

Placebo

CHF6297 (Part 4) DRUG

Twice daily doses of CHF6297 for 7 days

CHF6297 Active

Placebo (Part 4) DRUG

Twice daily doses of placebo matching CHF6297 for 7 days

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (2)

Quotient Clinical

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

Related Links

• Study Record on EU Clinical Trials Register including results

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stuart Mair, MD

  Quotient Clinical

  PRINCIPAL INVESTIGATOR

• Dave Singh, MD

  Medicines Evaluation Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2016
• First Posted: June 28, 2016
• Study Start: January 22, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: April 17, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)