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

Phase 1

Completed

• Conditions: Non-Cystic Fibrosis Bronchiectasis; Cystic Fibrosis
• Interventions: Drug: Placebo (Part 1 - SAD); Drug: CHF6333 (Part 1 - SAD); Drug: CHF6333 (Part 2 - MAD); Drug: Placebo (Part 2 - MAD)

• Registration Number: NCT03056326
• Lead Sponsor: Chiesi Farmaceutici S.p.A.

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

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11
• Study First Submitted: 2017-02-03
• Study First Submitted QC: 2017-02-14
• Study First Posted: 2017-02-17
• Primary Completion: 2017-07
• Study Completion: 2017-07
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-06
• Last Update Posted: 2017-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 72

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CHF6333 Active	CHF6333 (Part 2 - MAD)	-
Placebo	Placebo (Part 1 - SAD)	-
Placebo	Placebo (Part 2 - MAD)	-
CHF6333 Active	CHF6333 (Part 1 - SAD)	-

Primary Outcome Measures

Name	Time	Method
Adverse events	Part 1 from Day 1 to 5, Part 2 from Day 1 to 15	Treatment-related Adverse events
Heart Rate	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15	Change in Heart Rate (from ECG)
Clinical chemistry and haematology	Part 1 Day 1-5, Part 2 Day 1-15	change in Clinical chemistry and haematology parameters
Urinalysis	Part 1 Day 1-5, Part 2 Day 1-15	Change in urinalysis parameters
PR interval	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15	Change in PR interval (from ECG)
Holter recording abnormalities	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15	24h-holter ECG recording
Change in Vital signs	Part 1 from Day 1 to 5, Part 2 from Day 1 to 15	Blood pressure
QRS interval	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15	Change in QRS interval (from ECG)
QTcF interval	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15	Change in QTcF interval (from ECG)
FEV1	Part 1 Day 1-2, Part 2 Day 1-14-15	Change in FEV1 (Forced exhalation volume in the first second)

Secondary Outcome Measures

Name	Time	Method
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	maximum plasma concentration of CHF6333
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	Absolute plasma clearance
Volume of distribution (Vz/F)	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15	plasma volume of distribution
Urinary excretion (Ae)	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15	Amount of CHF6333 excreted in urine
fraction excreted (fe)	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15	Percentage of drug excreted in urine
Renal clearance (CLr)	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15

Trial Locations

Locations (1)

SGS Life Sciences; 🇧🇪 Antwerpen, Belgium