Clinical trial NCT03056326: A Study to Investigate Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of CHF6333 in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Cystic Fibrosis Bronchiectasis
Cystic Fibrosis
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2017-02-17
Enrollment: 72
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model description: Part 1: alternating cross-over design

Part 2: parallel design
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Adverse events
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1 to 15
measure: Change in Vital signs
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1 to 15
measure: Heart Rate
timeFrame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
measure: QTcF interval
timeFrame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
measure: PR interval
timeFrame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
measure: QRS interval
timeFrame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
measure: Holter recording abnormalities
timeFrame: Part 1 Day 1-2, Part 2 Day 1-2 and Day 14-15
measure: FEV1
timeFrame: Part 1 Day 1-2, Part 2 Day 1-14-15
measure: Clinical chemistry and haematology
timeFrame: Part 1 Day 1-5, Part 2 Day 1-15
measure: Urinalysis
timeFrame: Part 1 Day 1-5, Part 2 Day 1-15
Secondary outcomes:
measure: Area under the plasma concentration
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
measure: Peak plasma concentration (Cmax)
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
measure: Time to reach the maximum plasma concentration (tmax)
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
measure: Elimination half-life (t1/2)
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
measure: Clearance (CL/F)
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
measure: Volume of distribution (Vz/F)
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
measure: Urinary excretion (Ae)
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
measure: fraction excreted (fe)
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
measure: Renal clearance (CLr)
timeFrame: Part 1 from Day 1 to 5, Part 2 from Day 1-2 and Day 14-15
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: SGS Life Sciences
Study officials:
affiliation: SGS Life Sciences, a division of SGS Belgium NV
name: Frédéric Vanhoutte
role: PRINCIPAL_INVESTIGATOR
References: