Study of CHF6366 in healthy subjects and patients with Asthma and COPD
- Conditions
- Patients with Chronic Obstructive Pulmonary Disease (COPD)Patients with AsthmaMedDRA version: 20.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersMedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2015-005551-27-GB
- Lead Sponsor
- Chiesi Farmaceutici
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 106
Part 1
-Healthy male subjects, 18-55yrs
-BMI between 18.5 and 32.0kg/m2
-Non-or ex-smokers who smoked <5 pack years and stopped smoking >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 <5 pack years and stopped smoking >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
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 <3.8 mmol/L
- Taken non-permitted concomitant medications, including vitamins and herbal remedies such as St John’s Wort, in the predefined period
- Heavy caffeine drinker (>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 <90 or >140 (as mean of 2 measures after at least 5 minute of resting)
- Unstable and uncontrolled blood pressure <60 or >90 mmHg (as mean of 2 measures)
- Abnormal resting ECG (heart rate <40 bpm or >10 bpm, PR interval <120 or >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method