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

Prior treatment

• Respiratory infection or COPD exacerbation within 6 weeks (2 months if it resulted in hospitalization) prior to screening
• Any contraindication to LABA or LAMA drugs or to Inhaled corticosteroids

Other illness

• History or current diagnosis of asthma or ACOS (asthma-COPD overlap syndrome)
• Clinically relevant respiratory conditions (other than COPD)
• Hepatic impairment
• Any type of cancer within 5 years

Lab values

• 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).
• Severe renal impairment eGFR \< 30

Age

• Woman of childbearing age without effective contraception

Other

• 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)
• Pregnancy or breastfeeding
• Patients under guardianship
• Refuse or incapacity to give an informed consent
• Absence of social insurance

• 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