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

Cystic Fibrosis Clinical Trial

— CHF6333 FIH  

Official title:

A Phase I, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Inhaled CHF 6333 After Single and Repeated Ascending Doses in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03056326
• Other study ID #: CCD-06333AA1-01
• Secondary ID: 2015-005552-94
• Status: Completed
• Phase: Phase 1
• First received: February 3, 2017
• Last updated: November 6, 2017
• Start date: November 2016
• Est. completion date: July 2017

Study information

• Verified date: November 2017
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Bronchiectasis
• Cystic Fibrosis
• Fibrosis
• Non-Cystic Fibrosis Bronchiectasis

Intervention

Drug:
• CHF6333 (Part 1 - SAD)
Single doses of CHF6333 at each period
• Placebo (Part 1 - SAD)
Single doses of placebo matching CHF6333 at each period
• CHF6333 (Part 2 - MAD)
once daily multiple doses of CHF6333 for 14 days
• Placebo (Part 2 - MAD)
once daily multiple doses of placebo matching CHF6333 for 14 days

Locations

Country	Name	City	State
Belgium	SGS Life Sciences	Antwerpen

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Treatment-related Adverse events	Part 1 from Day 1 to 5, Part 2 from Day 1 to 15
Primary	Change in Vital signs	Blood pressure	Part 1 from Day 1 to 5, Part 2 from Day 1 to 15
Primary	Heart Rate	Change in Heart Rate (from ECG)	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Primary	QTcF interval	Change in QTcF interval (from ECG)	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Primary	PR interval	Change in PR interval (from ECG)	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Primary	QRS interval	Change in QRS interval (from ECG)	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Primary	Holter recording abnormalities	24h-holter ECG recording	Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
Primary	FEV1	Change in FEV1 (Forced exhalation volume in the first second)	Part 1 Day 1-2, Part 2 Day 1-14-15
Primary	Clinical chemistry and haematology	change in Clinical chemistry and haematology parameters	Part 1 Day 1-5, Part 2 Day 1-15
Primary	Urinalysis	Change in urinalysis parameters	Part 1 Day 1-5, Part 2 Day 1-15
Secondary	Area under the plasma concentration		Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
Secondary	Peak plasma concentration (Cmax)	maximum plasma concentration of CHF6333	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
Secondary	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
Secondary	Elimination half-life (t1/2)		Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
Secondary	Clearance (CL/F)	Absolute plasma clearance	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
Secondary	Volume of distribution (Vz/F)	plasma volume of distribution	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
Secondary	Urinary excretion (Ae)	Amount of CHF6333 excreted in urine	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
Secondary	fraction excreted (fe)	Percentage of drug excreted in urine	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
Secondary	Renal clearance (CLr)		Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15