Clinical trial NCT06746064: A Study to Investigate the Safety, Tolerability and Pharmacokinetics of Inhaled CHF10073 After Single and Multiple Doses in Healthy Volunteers
Official title: A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of CHF10073 After Single and Multiple Ascending Doses in Healthy Volunteers Via Inhalation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pulmonary Fibrosis
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2024-12-24
Enrollment: 132
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 - SAD (single ascending dose): Randomised, double-blind, placebo-controlled, single-dose escalation, parallel-group design in HVs.

Part 2 - MAD (multiple ascending dose): Randomised, double-blind, placebo-controlled, repeated-dose escalation, parallel-group design in HVs; Part 3: Non-randomised, open-label, single dose design in HVs
Primary purpose: OTHER

Brief summary: The objective of this study is to assess the safety and tolerability of single ascending doses of inhaled CHF10073 (Part 1 of the study) and multiple ascending doses of CHF10073 (Part 2 of the study). The study will also evaluate the PK profile of study drug in plasma and urine after single and repeated administrations of CHF10073.

In addition, this study will also investigate the metabolites profile of CHF10073 in plasma, urine and faeces (Part 2 of the study) and the PK profile of CHF10073 in the lungs after bronchoalveolar lavage (BAL) (Part 3 of the study).


Eligibility criteria: Inclusion Criteria:

* Subject's written informed consent;
* Healthy males aged 18-55 years;
* Understanding of the study procedures and the correct use of the inhalers;
* BMI between 18.5 and 30.0 kg/m2;
* Non- or ex-smokers (\<5 pack-years and stopped smoking \>1 year prior to screening);
* Good physical and mental status;
* Vital signs within normal limits; body temperature \<37.5°C;
* 12-lead digitised ECG in triplicate considered as normal;
* Lung function measurements within normal limits;
* Males with pregnant or non-pregnant WOCBP partners must be willing to use contraception

Exclusion Criteria:

* Recent participation in another clinical trial;
* Clinically significant abnormal 24h Holter ECG (Part 1 and 2);
* Clinically relevant and uncontrolled medical disorders ;
* Subjects with history of respiratory diseases ;
* Presence of any current or recent infection;
* Clinically relevant abnormal laboratory values;
* Abnormal liver enzymes;
* Positive results from the Hepatitis serology results;
* Positive HIV-1 or HIV-2 serology results ;
* Recent blood donation or blood loss (≥450 mL) ;
* Heavy caffeine drinker ;
* Recent use of any kind of electronic smoking devices;
* Documented history of alcohol abuse within 12 months prior to screening ;
* Documented history of drug abuse within 12 months prior to screening ;
* Intake of non-permitted concomitant medications ;
* Known intolerance and/or hypersensitivity to any of the study excipients ;
* Unsuitable veins for repeated venipuncture;
* Part 3 only: contraindication to the BAL procedure;
* Part 3 only: recent lower respiratory tract infections

Primary outcomes:
measure: Adverse events and adverse drug reactions
timeFrame: Through study completion, around 8 weeks in Part 1, from 10 to 13 weeks in Part 2 and for about 7-8 weeks in Part 3
measure: Vital signs (Systolic and diastolic Blood Pressure)
timeFrame: From screening up to 28 days post-dose
measure: Absolute Values for 12-lead Electrocardiogram (ECG) Recording of HR (heart rate), HR from 0 to 24 hours, hourly HR
timeFrame: From screening up to 28 days post-dose
measure: Absolute Values for 12-lead ECGs Recording of Intervals
timeFrame: From screening up to 28 days post-dose
measure: Change from Baseline for Post-dose 12-lead ECGs Recording of HR, HR from 0 to 24 hours, hourly HR
timeFrame: From screening up to 28 days post-dose
measure: Change from Baseline for Post-dose 12-lead ECGs Recording of Intervals
timeFrame: From screening up to 28 days post-dose
measure: Number and percentage of subjects with abnormal actual QTcF (Fridericia-corrected QT Interval).
timeFrame: Part 1 and 2 only: From screening up to 28 days post-dose
measure: Number and percentage of subjects with abnormal change from the baseline of QTcF and HR from 0 to 24 hours
timeFrame: Part 1 and 2 only: From screening up to 28 days post-dose
measure: Number of subjects and percentages by treatment with abnormal parameters derived from 24h Holter ECG recording (total pauses >2.5 secs, atrial fibrillation and atrial flutter, ventricular runs, PAC burden, PVC burden and aberrant morphologies)
timeFrame: Part 1 and 2 only: From screening up to 28 days post-dose
measure: Number of subjects with abnormal blood laboratory test results
timeFrame: From screening up to 28 days post-dose
measure: Number of subjects with abnormal urine laboratory test results
timeFrame: From screening up to 28 days post-dose
measure: Spirometry (FEV1 (Forced exhalation volume in the first second))
timeFrame: From screening up to 28 days post-dose
measure: Cough recording: percentage of days with cough episodes during the treatment period
timeFrame: Part 2 only: From first dosing up to 28 days post-dose
measure: Cough recording: average VAS (visual analogue scale))
timeFrame: Part 2 only: From first dosing up to 28 days post-dose
Secondary outcomes:
measure: CHF10073 plasma AUCt (Area Under the Curve from time 0 to time t)
timeFrame: From first dosing up to 28 days post-dose
measure: CHF10073 plasma AUCinf (Area Under the Curve from time 0 Extrapolated to Infinity)
timeFrame: From first dosing up to 28 days post-dose
measure: CHF10073 plasma Cmax (Maximum Plasma Concentration)
timeFrame: From first dosing up to 28 days post-dose
measure: CHF10073 plasma tmax (Time to Maximum Plasma Concentration)
timeFrame: From first dosing up to 28 days post-dose
measure: CHF10073 plasma elimination half-life
timeFrame: From first dosing up to 28 days post-dose
measure: CHF10073 plasma apparent clearance (CL/F)
timeFrame: From first dosing up to 28 days post-dose
measure: CHF10073 plasma apparent volume of distribution (Vz/F)
timeFrame: From first dosing up to 28 days post-dose
measure: CHF10073 urine amount excreted (Ae)
timeFrame: Part 1 and 2 only: From first dosing up to 28 days post-dose
measure: CHF10073 urine faction excreted (fe)
timeFrame: Part 1 and 2 only: From first dosing up to 28 days post-dose
measure: CHF10073 renal clearance (CLr)
timeFrame: Part 1 and 2 only: From first dosing up to 28 days post-dose
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: SGS Belgium NV Clinical Pharmacology Unit
Study officials:
affiliation: SGS Belgium
name: Frédéric Vanhoutte, MD
role: PRINCIPAL_INVESTIGATOR
References: