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

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

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

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Non-Cystic Fibrosis Bronchiectasis
• Intervention / Treatment: Drug: CHF6333 (Part 1 - SAD); Drug: CHF6333 (Part 2 - MAD); Drug: Placebo (Part 1 - SAD); Drug: Placebo (Part 2 - MAD)

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • SGS Life Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo (Part 1 - SAD); Single doses of placebo matching CHF6333 at each period; Drug: Placebo (Part 2 - MAD); once daily multiple doses of placebo matching CHF6333 for 14 days
Experimental: CHF6333 Active	Drug: CHF6333 (Part 1 - SAD); Single doses of CHF6333 at each period; Drug: CHF6333 (Part 2 - MAD); once daily multiple doses of CHF6333 for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	maximum plasma concentration of CHF6333	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)	Absolute plasma clearance	Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
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
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
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
Renal clearance (CLr)		Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Frédéric Vanhoutte, SGS Life Sciences, a division of SGS Belgium NV

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: February 3, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 17, 2017

Study Record Updates

• Last Update Posted (Actual): November 7, 2017
• Last Update Submitted That Met QC Criteria: November 6, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Bronchial Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Bronchiectasis; Cystic Fibrosis
• Other Study ID Numbers: CCD-06333AA1-01; 2015-005552-94 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided