Impact of Long-acting Bronchodilator- -Corticoid Inhaled Therapy on Ventilation, Lung Function and Breathlessness

Inclusion criteria

• Provision of signed informed consent prior to any study specific procedure
• Female or male subjects aged 40-75 years inclusive at the time of enrolment (Visit 1)
• Documented history of COPD with a post-bronchodilator FEV1/FVC <0.70 and a post-bronchodilator 30 % < FEV1 <70% of predicted normal value (according to ERS 1993 reference values for spirometry ) at screening
• Smoking history > 10 pack-years
• Baseline significant dyspnea with a mMRC ≥ 2

Exclusion criteria

• History or current diagnosis of asthma or ACOS (asthma-COPD overlap syndrome)
• Respiratory infection or COPD exacerbation within 6 weeks (2 months if it resulted in hospitalization) prior to screening
• Clinically significant or relevant cardiovascular conditions, laboratory tests, electrocardiogram (ECG) parameters:

• Unstable angina/acute coronary syndrome, or Coronary Artery Bypass Grafting (CABG), Percutaneous Coronary Intervention (PCI) or myocardial infarction within the past 6 months.
• Congestive heart failure New York Heart Association (NYHA) class III/IV.
• Structural heart disease (hypertrophic cardiomyopathy, significant valvular disease).
• Paroxysmal (within the past 6 months) or symptomatic chronic cardiac tachyarrhythmia.
• Left bundle branch or high-degree AV block (second degree AV block type 2 and third degree AV block) unless the patient has a pacemaker.
• Sinus node dysfunction with pauses.
• Ventricular pre-excitation and/or Wolff-Parkinson-White syndrome.
• QTcF interval >470 msec (QT interval corrected using Fridericia's formula; QTcF=QT/[RR1/3]).
• Any other ECG abnormality deemed clinically significant by the Investigator.
• Bradycardia with ventricular rate < 45 bpm.
• Uncontrolled hypertension (> 165/95 mmHg).
• Clinically relevant respiratory conditions (other than COPD)
• Severe renal impairment eGFR < 30
• Hepatic impairment
• Narrow-angle glaucoma that, in the opinion of the Investigator, has not been adequately treated.
• Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that is clinically significant
• Patients not able to perform IOS, spirometry, plethysmography, or VT acquisition (10 min)
• Any contraindication to LABA or LAMA drugs or to Inhaled corticosteroids
• Pregnancy or breastfeeding
• Woman of childbearing age without effective contraception
• Any type of cancer within 5 years
• Patients under guardianship
• Refuse or incapacity to give an informed consent
• Absence of social insurance