Efficacy, safety and tolerability of two Fixed-Dose Combinations of Aclidinium bromide with two doses of Formoterol fumarate compared with Aclidinium bromide, Formoterol fumarate and placebo all administered twice daily in stable, moderate to severe Chronic Obstructive Pulmonary Disease patients

INTERVENTION: Product Name: Aclidinium bromide 200 µg/Formoterol fumarate 6 µg Product Code: LAS40464 Pharmaceutical Form: Inhalation powder INN or Proposed INN: Aclidinium bromide CAS Number: 320345‐99‐1 Current Sponsor code: LAS34273 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed INN: Formoterol fumarate CAS Number: 43229‐80‐7 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 6‐ Pharmaceutical form of the placebo: Inhalation powder Route of administration of the placebo: Inhalation use Product Name: Aclidinium bromide 200 µg/Formoterol fumarate 12 µg Product Code: LAS40464 Pharmaceutical Form: Inhalation powder INN or Proposed INN: Aclidinium bromide CAS Number: 320345‐99‐1 Current Sponsor code: LAS34273 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed INN: Formoterol fumarate CAS Number: 43229‐80‐7 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 12‐ Pharmaceutical form of the placebo: Inhalation powder Route of administration of the placebo: Inhalation use Product Name: Aclidinium bromide 200 µg Product Code: LAS34273 Pharmaceutical Form: Inhalation powder INN or Proposed INN: Aclidinium bromide CAS Number: 320345‐99‐1 Current Sponsor code: LAS34273 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Inhalation powder Route of administration of the placebo: Inhalation use Product Name: Formoterol fumarate 12 µg Product Code: Formoterol Pharmaceutical Form: Inhalation powder INN or Proposed INN: Formoterol fumarate CAS Number: 43229‐80‐7 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 12‐ Pharmaceutical form of the placebo: Inhalation powder Route of administration of the placebo: Inhalation use CONDITION: Moderate to severe chronic obstructive pulmonary disease (COPD) ; MedDRA version: 12.0 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease PRIMARY OUTCOME: Main Objective: To assess the efficacy, safety and tolerability of the two fixed‐dose combinations of aclidinium bromide and formoterol fumarate compared to placebo, all administered twice daily in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Primary end point(s): Primary Efficacy variable:; Change from baseline in normalised FEV1 area under the curve over the 12h after morning IMP administration (FEV1 AUC0‐12) at Day 14. Secondary Objective: To determine which of the two combinations provide the greater benefit in terms of efficacy, safety and tolerability. INCLUSION CRITERIA: 1. Adult male or non‐pregnant, non‐lactating female aged between 40 and 80 years old, both inclusive. Female of childbearing potential must have a negative pregnancy test at Screening and be using a medically acceptable method of contraception (either double‐barrier contraception or a barrier method plus a spermicidal or hormonal agent). (A female is considered to be of childbearing potential unless she is at least 1 year postmenopausal or surgically sterile (defined as having a hysterectomy or tubal ligation)). 2. Patient with a clinical diagnosis of stable moderate to severe COPD (stages II and III) according to the GOLD classification (http://www.goldcopd.com). 3. Current, or ex‐cigarette smoker with a smoking history of at least 10 pack‐years. Pack‐years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person has smoked. For example,