A Study in Patients With Chronic Obstructive Pulmonary Disease (FAIR)

• Changes from baseline in FEV1, FVC, FEV1/FVC, IVC/FVC, RV, TLC, RV/TLC, FRC, FRC/TLC, RV/VC, Raw, eff and sGaw, eff. [ Time Frame: At day 84 ] [ Designated as safety issue: No ]
• Changes from baseline in airways resistance (R5, R20, R5-20) and reactance at 5 Hertz (X5) (in a subset of at least 50% of patients from pre-selected sites); [ Time Frame: at day 84 ] [ Designated as safety issue: No ]
• Changes from baseline in COPD symptom scores (for each single score and the total score); [ Time Frame: At day 84 ] [ Designated as safety issue: No ]
• Change from baseline in percentage of COPD symptom-free days; [ Time Frame: At day 84 ] [ Designated as safety issue: No ]
• Change from baseline in rescue salbutamol or ipratropium bromide consumption (puffs per day); [ Time Frame: At day 84 ] [ Designated as safety issue: No ]
• Change from baseline in percentage of rescue salbutamol or ipratropium bromide-free days; [ Time Frame: At day 84 ] [ Designated as safety issue: No ]
• Transition Dyspnoea Index (TDI) score; [ Time Frame: At day 84 (V4) ] [ Designated as safety issue: No ]
• Clinical COPD Questionnaire (CCQ); [ Time Frame: At screening (day -28), at baseline (day 0) and at the end of trial (day 84) ] [ Designated as safety issue: No ]
• Physical activity (by means of pedometer); [ Time Frame: Each day of the two weeks before each clinic visit ] [ Designated as safety issue: No ]
• Nasal brushing (mRNA expression); [ Time Frame: At screening (day -28), at baseline (day 0) and at the end of trial (day 84) ] [ Designated as safety issue: No ]
• Number of patients with COPD exacerbations. [ Time Frame: From pre-screening (day -35) to the end of trial (day 84) ] [ Designated as safety issue: No ]

The purpose of the present study is to demonstrate the higher efficacy of small particles Foster® 100/6 (two puffs b.i.d.) versus large particles Symbicort® 200/6 (two inhalations b.i.d.), in terms of residual volume reduction over a 12-week treatment period in Chronic Obstructive Pulmonary Disease (COPD) patients.

Chronic obstructive pulmonary disease (COPD) is an incurable, debilitating and progressive disease that can be fatal. The recent Global Burden of Disease Study ranks COPD as the 6th leading cause of mortality and the 12th leading cause of morbidity world-wide. Furthermore, trends in the use of medical care resources indicate that the economic cost of COPD continues to rise in direct relation to the ageing population, the increase in prevalence of disease and the cost of new and existing medical and public health interventions.

• Drug: Foster® 100/6 µg/unit dose
  Foster® (beclomethasone dipropionate 100 µg plus formoterol 6 µg/unit dose), 2 inhalations b.i.d. (daily dose of BDP "extrafine" 400 µg plus FF 24 µg).
• Drug: Symbicort® Turbohaler® 200/6 μg/actuation
  Symbicort® Turbohaler® (budesonide 200 μg plus formoterol fumarate 6 μg/actuation), 2 inhalations b.i.d. (daily dose of BUD 800 μg plus FF 24 μg).

• Experimental: Foster®
  Foster® (beclomethasone dipropionate 100 µg plus formoterol 6 µg/unit dose), 2 inhalations b.i.d. (daily dose of BDP "extrafine" 400 µg plus FF 24 µg).
  Intervention: Drug: Foster® 100/6 µg/unit dose
• Active Comparator: Symbicort® Turbohaler®
  Symbicort® Turbohaler® (budesonide 200 μg plus formoterol fumarate 6 μg/actuation), 2 inhalations b.i.d. (daily dose of BUD 800 μg plus FF 24 μg).
  Intervention: Drug: Symbicort® Turbohaler® 200/6 μg/actuation

Inclusion Criteria:

1. Male or female patients aged ≥ 40 years, who have signed an Informed Consent form prior to initiation of any study-related procedure or when applicable written informed consent obtained by legal representative.

2. Outpatients with a clinical diagnosis of moderate to severe COPD and including:

   1. Smoking history of at least 10 pack years defined as [(number of cigarettes smoked per day) x (number of years of smoking)] / 20, both current and ex-smokers are eligible.
   2. Regular use of bronchodilators (e.g. β2-agonist, anticholinergics) in the 2 months before visit 1.
   3. Post-bronchodilator FEV1 < 65% of the predicted normal value at visit 1.
   4. Post-bronchodilator FEV1/FVC < 0.7 at visit 1.
   5. An increase in FEV1 < 15% and < 200 mL from baseline following administration of 400 µg of salbutamol at visit 1.
   6. Plethysmographic Functional Residual Capacity (FRC) > 120% of the predicted normal value (at visit 1 and visit 2).
   7. A Baseline Dyspnoea Index (BDI) focal score less or equal to 10 (at visit 1 and at visit 2).
3. A cooperative attitude and ability to be trained to the proper use of pMDI and DPI (Turbohaler®, inspiratory flow-driven, multidose powder inhaler) inhalers.

Main Exclusion Criteria:

1. Diagnosis of asthma or other clinically or functionally relevant respiratory disorders (other than COPD) which may interfere with data interpretation according to the investigator's opinion.
2. Clinically unstable concurrent disease: e.g. hyperthyroidism, diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; cardiovascular disease (e.g. coronary artery disease, hypertension, heart failure); gastrointestinal disease (e.g. active peptic ulcer); neurological disease; haematological disease; autoimmune disorders, or other which may impact the evaluation of the results of the study according to investigator's judgement.
3. Patients with COPD exacerbation and/or symptomatic infection of the airways requiring antibiotic therapy (at least 5 days) in the 2 months prior to screening and during the study period.
4. Patients treated with depot corticosteroids in the 2 months preceding the visit 1 and during the run-in period.
5. Major surgery in the previous 3 months and during the trial which may affect patient's compliance in study procedures (e.g. plethysmography).
6. Patients requiring chronic mechanical ventilation for COPD.