A Study to Investigate Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of CHF6333 in Healthy Subjects

NCT03056326 | Completed Phase 1

• 2 other identifiers: CCD-06333AA1-012015-005552-94
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Human Neutrophil Elastase (HNE) plays a pivotal role in innate immunity and in neutrophilic lung inflammation that characterized many diseases. CHF 6333 is a potent and 24h-durable inhibitor of HNE, developed as Dry Powder Inhaler (DPI) formulation. This study is designed to investigate the tolerability, safety and pharmacokinetics of inhaled CHF6333 DPI in healthy male subjects. The study will comprise two parts: Part 1 will consist of two alternated cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Single Ascending Dose (SAD) of CHF6333. Part 2 will consist of four sequential cohorts of healthy male subjects to assess the safety, tolerability and pharmacokinetics of Multiple Ascending Dose (MAD) of CHF6333

Conditions

Non-Cystic Fibrosis Bronchiectasis; Cystic Fibrosis

Outcome Measures

Primary Outcomes (10)

• Adverse events

  Treatment-related Adverse events

  Part 1 from Day 1 to 5, Part 2 from Day 1 to 15

• Change in Vital signs

  Blood pressure

  Part 1 from Day 1 to 5, Part 2 from Day 1 to 15

• Heart Rate

  Change in Heart Rate (from ECG)

  Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

• QTcF interval

  Change in QTcF interval (from ECG)

  Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

• PR interval

  Change in PR interval (from ECG)

  Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

• QRS interval

  Change in QRS interval (from ECG)

  Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

• Holter recording abnormalities

  24h-holter ECG recording

  Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

• FEV1

  Change in FEV1 (Forced exhalation volume in the first second)

  Part 1 Day 1-2, Part 2 Day 1-14-15

• Clinical chemistry and haematology

  change in Clinical chemistry and haematology parameters

  Part 1 Day 1-5, Part 2 Day 1-15

• Urinalysis

  Change in urinalysis parameters

  Part 1 Day 1-5, Part 2 Day 1-15

Secondary Outcomes (9)

• Area under the plasma concentration

  Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15

• Peak plasma concentration (Cmax)

  Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15

• Time to reach the maximum plasma concentration (tmax)

  Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15

• Elimination half-life (t1/2)

  Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15

• Clearance (CL/F)

  Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15

Study Arms (2)

CHF6333 Active

EXPERIMENTAL

Drug: CHF6333 (Part 1 - SAD); Drug: CHF6333 (Part 2 - MAD)

Placebo

PLACEBO COMPARATOR

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

Interventions

CHF6333 (Part 1 - SAD) DRUG

Single doses of CHF6333 at each period

CHF6333 Active

Placebo (Part 1 - SAD) DRUG

Single doses of placebo matching CHF6333 at each period

Placebo

CHF6333 (Part 2 - MAD) DRUG

once daily multiple doses of CHF6333 for 14 days

CHF6333 Active

Placebo (Part 2 - MAD) DRUG

once daily multiple doses of placebo matching CHF6333 for 14 days

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male subjects aged 18-55 years
• BMI between 18-30 kg/m2
• 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

You may not qualify if:

• 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
• Unsuitable veins for repeated venepuncture

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

SGS Life Sciences

Antwerp, 2060, Belgium

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Frédéric Vanhoutte

  SGS Life Sciences, a division of SGS Belgium NV

  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

Model Details: Part 1: alternating cross-over design Part 2: parallel design

Study Record Dates

• First Submitted: February 3, 2017
• First Posted: February 17, 2017
• Study Start: November 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: November 7, 2017

Record last verified: 2017-11

Locations

BE (1)