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

Chiesi Farmaceutici S.p.A.72 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Non-Cystic Fibrosis Bronchiectasis Cystic Fibrosis

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Adverse events

Treatment-related Adverse events

Time frame: Part 1 from Day 1 to 5, Part 2 from Day 1 to 15

Change in Vital signs

Blood pressure

Time frame: Part 1 from Day 1 to 5, Part 2 from Day 1 to 15

Heart Rate

Change in Heart Rate (from ECG)

Time frame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

QTcF interval

Change in QTcF interval (from ECG)

Time frame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

PR interval

Change in PR interval (from ECG)

Time frame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

QRS interval

Change in QRS interval (from ECG)

Time frame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15

Holter recording abnormalities

24h-holter ECG recording

Time frame: 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)

Time frame: Part 1 Day 1-2, Part 2 Day 1-14-15

Clinical chemistry and haematology

change in Clinical chemistry and haematology parameters

Time frame: Part 1 Day 1-5, Part 2 Day 1-15

Urinalysis

Change in urinalysis parameters

Time frame: Part 1 Day 1-5, Part 2 Day 1-15