A Study to Investigate the Safety, Tolerability and Pharmacokinetics of Inhaled CHF10073 After Single and Multiple Doses in Healthy Volunteers and the Effect of Itraconazole on CHF10073 Exposure

Chiesi Farmaceutici S.p.A.155 enrolled

Overview

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). In addition, the effect of multiple doses of itraconazole on the pharmacokinetic profile of CHF10073 will be investigated (Part 4 of the study).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

155

Conditions

Pulmonary Fibrosis

Interventions

Eligibility

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

Medical Language ↔ Plain English

Inclusion Criteria: * Subject's written informed consent; * Healthy male (Part 1 to 4) or female (Part 4) 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 women of childbearing potential (WOCBP) partners must be willing to use contraception * Part 4 only: women of non-childbearing potential (WONCBP) or WOCBP with fertile male parters 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 * Part 4 only: known allergy to antifungal medicines; * Part 4 and females only: pregnant or lactating women

Outcomes

Primary Outcomes

Adverse events and adverse drug reactions

Time frame: Through study completion, around 8 weeks in Part 1, from 10 to 13 weeks in Part 2, for about 7-8 weeks in Part 3 and for about 15 up to 17 weeks in Part 4

Vital signs (Systolic and diastolic Blood Pressure)

Time frame: From screening up to 42 days post-dose

Absolute Values for 12-lead Electrocardiogram (ECG) Recording of HR (heart rate), HR from 0 to 24 hours, hourly HR

Time frame: From screening up to 28 days post-dose

Absolute Values for 12-lead ECGs Recording of Intervals

Intervals recorded: PR, QRS, QT, QTcF

Time frame: From screening up to 28 days post-dose

Change from Baseline for Post-dose 12-lead ECGs Recording of HR, HR from 0 to 24 hours, hourly HR

Time frame: From screening up to 28 days post-dose

Change from Baseline for Post-dose 12-lead ECGs Recording of Intervals

Intervals recorded: PR, QRS, QT, QTcF

Time frame: From screening up to 28 days post-dose

Number and percentage of subjects with abnormal actual QTcF (Fridericia-corrected QT Interval).

Time frame: Part 1 and 2 only: From screening up to 28 days post-dose

Number and percentage of subjects with abnormal change from the baseline of QTcF and HR from 0 to 24 hours

Time frame: Part 1 and 2 only: From screening up to 28 days post-dose

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)

Time frame: Part 1 and 2 only: From screening up to 28 days post-dose

Number of subjects with abnormal blood laboratory test results

Quantitative laboratory parameters (chemistry and haematology) will be summarised by treatment as absolute value and change from baseline using descriptive statistics.

Time frame: From screening up to 28 days post-dose

Number of subjects with abnormal urine laboratory test results

Time frame: From screening up to 28 days post-dose

Spirometry (FEV1 (Forced exhalation volume in the first second))

Time frame: From screening up to 28 days post-dose

Cough recording: percentage of days with cough episodes during the treatment period

Time frame: Part 2 only: From first dosing up to 28 days post-dose

Cough recording: average VAS (visual analogue scale))

Time frame: Part 2 only: From first dosing up to 28 days post-dose

CHF10073 plasma AUCt (Area Under the Curve from time 0 to time t)

Time frame: From first dosing up to 42 days post-dose

CHF10073 plasma Cmax (Maximum Plasma Concentration)

Time frame: From first dosing up to 42 days post-dose

Secondary Outcomes

CHF10073 plasma AUCinf (Area Under the Curve from time 0 Extrapolated to Infinity)

Time frame: From first dosing up to 42 days post-dose

CHF10073 plasma tmax (Time to Maximum Plasma Concentration)

Time frame: From first dosing up to 42 days post-dose

CHF10073 plasma elimination half-life

Time frame: From first dosing up to 42 days post-dose

CHF10073 plasma apparent clearance (CL/F)

Time frame: From first dosing up to 42 days post-dose

CHF10073 plasma apparent volume of distribution (Vz/F)

Time frame: From first dosing up to 42 days post-dose

CHF10073 urine amount excreted (Ae)

Time frame: Part 1, 2 and 4 : From first dosing up to 28 days post-dose

CHF10073 urine faction excreted (fe)

Time frame: Part 1, 2 and 4: From first dosing up to 28 days post-dose

CHF10073 renal clearance (CLr)

Time frame: Part 1, 2 and 4: From first dosing up to 28 days post-dose

A Study to Investigate the Safety, Tolerability and Pharmacokinetics of Inhaled CHF10073 After Single and Multiple Doses in Healthy Volunteers and the Effect of Itraconazole on CHF10073 Exposure

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes