Patients with Chronic Obstructive Pulmonary Disease (COPD) Patients with Asthma MedDRA version: 20.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: CHF 6366
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: CHF 6366
Current Sponsor code: CHF 6366.01
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: ran
Sponsors
Chiesi Farmaceutici
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1 - Healthy male subjects, 18-55yrs - BMI between 18.5 and 32.0kg/m2 - Non-or ex-smokers who smoked 1 year - Vital signs within normal limits at screen and prior to randomisation: Diastolic BP 50-90, Systolic BP 90-140 (2 measures after at least 5 minutes resting. For eligibility purposes, the 2 single measurements will be considered). Body temperature 36-37.2ºC - 12-lead ECG considered as normal (45= Heart rate =85bpm, 110ms= PR =200 ms, QRS =120 ms, QTcF =450 ms) at screen visit and prior to randomisation - Lung function measurements within normal limits at screen and prior to randomisation: FEV1 equal to or more than 80% of predicted for the subject’s normal value according to GLI, ERS Task Force Lung Function Reference Values and FEV1/FVC ratio >0.70 Part 2 - Male and female subjects, 18-75yrs - Clinical diagnosis of mild persistent asthma (according to GINA guidelines) for at least 6 months prior to screen - Non-or ex-smokers who smoked 1 year - Vital signs within normal limits at screen and prior to randomisation: Diastolic BP 50-90, Systolic BP 90-150. Body temperature 36-37.2ºC - Normal resting ECG (after 5 minutes resting) (heart rate 45 to 100 bpm, PR 120 to 200 msec, QRS =120 msec, QTcF =450 msec (male) and QTcF =470 (female), - Screen FEV1 value of =70% of the predicted normal value after a washout of at least 8h for short-acting beta2-agonists and 14 days for long-acting beta2-agonists or long acting antimuscarinic - FEV1 reversibility of = 12% or 200ml over the baseline value within 20-30min after inhalation of 400 µg of salbutamol - Using intermittent salbutamol and/or subjects on a stable dose or regimen of low dose ICS at least 4 weeks prior to screen and between screening and first dose - Otherwise healthy as determined by medical history, physical examination, 12-lead ECG findings Part 3 - Male and female adults, aged 40-75yrs - Vital signs at screen and prior to randomisation: Diastolic BP 50-90, Systolic BP 90-160. Body temperature 36-37.2ºC - Normal resting ECG (after 5 minutes resting) (HR 50 to 100 bpm, PR interval 120 to 200 msec, QRS duration <120 msec, QTcF <450 msec (male) and <470 msec (female)) - Outpatients with diagnosis of COPD (according to current GOLD guidelines) - A smoking history of at least 10 pack years, current smokers and ex-smokers are eligible - A post-bronchodilator 40%= FEV1 <80% of the predicted normal value, post-bronchodilator FEV1/FVC <0.7 with salbutamol - Treated with a stable therapy for at least 1 month prior to screen with any of the below: - Short acting ß2-agonist and/or short acting anticholinergic prn, - inhaled long acting ß2-agonist and/or long-acting muscarinic antagonist, - fixed combination of inhaled long acting ß2-agonist and long-acting muscarinic antagonist - fixed combination of LABA/LAMA/ICS - ICS - Response to ipratropium bromide, an increase in FEV1 of =7 % starting 30-45min after inhalation of 80µg ipratropium bromide at screen visit - Response to salbutamol, an increase in FEV1 of =7 % starting 20-30min following inhalation of 400µg salbutamol MDI at screen visit Applicable to Parts 2 & 3 - Female subject of non-childbearing potential (WONCBP) defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per investigator’s request, post-menopausal status m
Exclusion criteria
Exclusion criteria: Part 1: - Female Subjects - History of sustained and non-sustained cardiac arrhythmias and subjects with a family history of sudden cardiac death - Blood donation or blood loss (=450 ml) less than 12 weeks prior to screen or randomisation - Clinically relevant and uncontrolled hepatic, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder - Serum K value 5 cups a day) - Positive urine test for cotinine - Treated within 2 months before screen and before the first dose with enzyme-inducing or inhibiting drugs - Treated within 4 weeks before screen with antibiotics Part 2: - Pregnant and/or breastfeeding women - Uncontrolled asthmatic patients according to GINA criteria - Medical history or current diagnosis of COPD or any other pulmonary disease other than asthma - History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit or of frequent exacerbations in the last year - Therapy for gastroesophageal reflux disease or patients with a medical history of GERD that leads to asthma symptoms - Change in dose, schedule, of ICS in the 4 weeks prior to screen or between screen and first dose - Hospitalization, emergency room admission or use of systemic corticosteroids for an asthma exacerbation in the 6 weeks prior to screen or between screen and first dose - Seasonal worsening of asthma and cannot complete the study outside the relevant allergen season - Systolic Blood pressure 140 (as mean of 2 measures after at least 5 minute of resting) - Unstable and uncontrolled blood pressure 90 mmHg (as mean of 2 measures) - Abnormal resting ECG (heart rate 10 bpm, PR interval 200 msec, QRS duration >120 msec, QTcF >450 msec, any variation from normal waves and tracts morphology - Treated within 2 months before screen with enzyme-inducing or inhibiting drugs Part 3: - Pregnant and/or breastfeeding women - Current diagnosis of asthma - Hospital admission for COPD exacerbation within 12 months prior to screen or before first dose - Hospitalization pneumonia within 3 months prior to screen or before first dose - Recent COPD exacerbations requiring oral/systemic steroids and/or antibiotics and/or oral or nebulized beta2-agonists or need for increased treatments for COPD - Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screen or before first dose - Use of beta-blockers with the exception of cardioselective ß1-blockers, if taken for at least 2 months prior to screen and maintained constant during the study - Unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease significant hepatic impairment significant renal impairment significant non-COPD pulmonary disease (e.g. TB, lung cancer) uncontrolled gastrointestinal disease, neurological disease uncontrolled hematological disease uncontrolled autoimmune disorders - Abnormal resting ECG - Serum potassium levels below the lower limit of laboratories normal range - Diagnosis or a history of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that would prevent use of anticholinergic - Treated with quinidine, quinidine-like anti arrhythmic and any medication with a potential for QT prolongation 24h prior to screen - Changes in dose, sc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of single ascending doses of CHF 6366 in healthy male volunteers, of repeated ascending doses in male and female asthmatic patients and of a single dose in male COPD patients;Secondary Objective: - To investigate the pharmacokinetic (PK) profile of CHF 6366 and its metabolites CHF 6387 and CHF 6361 in healthy volunteers, asthmatic and COPD patients. - To investigate the metabolite profiling and identification in plasma, urine and faeces. - To evaluate the pharmacodynamics of CHF 6366 in COPD patients;Primary end point(s): Safety variables (AEs, ADRs, ECG, vital signs, spirometry, laboratory data);Timepoint(s) of evaluation of this end point: each period of the study and across the study for AEs/ADRs | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic variables of CHF 6366 and metabolite profile Evaluation of pharmacodynamics (PD) of CHF 6366 in COPD patients ;Timepoint(s) of evaluation of this end point: Collection of blood samples, urine and faeces during each period of the study | — |
Countries
United Kingdom
Contacts
Public ContactClinical Program Manager
Chiesi Farmaceutici
Outcome results
None listed