Tiotropium+Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Obstructive Pulmonary Disease (COPD)

• FEV1 AUC0-3h response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Trough FEV1 response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• SGRQ total score (This endpoint will be evaluated after combining the data from this and the replicate study 1237.6) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

• TDI focal score (Key secondary endpoint; This endpoint will be evaluated after combining the data from this and the replicate study 1237.6) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FVC AUC0-3h response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Trough FVC response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FEV1 AUC0-12h response [L] in sub-set of patients with 12-hour PFTs [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FVC AUC0-12h response [L] in sub-set of patients with 12-hour PFTs [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FEV1 peak0-3h response [L] [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FVC peak0-3h response [L] [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

• TDI focal score (Key secondary endpoint; This endpoint will be evaluated after combining the data from this and the replicate study 1237.6) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FVC AUC0-3h response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Trough FVC response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FEV1 AUC0-12h response [L] in sub-set of patients with 12-hour PFTs [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FVC AUC0-12h response [L] in sub-set of patients with 12-hour PFTs [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FEV1 peak0-3h response [L] [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FEV1 response [L] at 5, 15 and 30 minutes, and at 1, 2 and 3 hours after inhalation of study medication [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FVC response [L] at 5, 15 and 30 minutes, and at 1, 2 and 3 hours after inhalation of study medication [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• FVC peak0-3h response [L] [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

The overall objective of this study is to assess the efficacy and safety of 52 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC (delivered by the RESPIMAT Inhaler) compared with the individual components ( tiotropium, olodaterol) (delivered by the RESPIMAT Inhaler) in patients with Chronic Obstructive Pulmonary Disease (COPD).

• Drug: tiotropium + olodaterol
  fixed dose combination
• Drug: tiotropium
  low dose
• Drug: olodaterol
  one dose only
• Drug: tiotropium
  high dose

• Experimental: tiotropium+olodaterol low dose FDC
  Once daily 2 puffs solution for inhalation Respimat
  Intervention: Drug: tiotropium + olodaterol
• Experimental: tiotropium+olodaterol high dose FDC
  Once daily 2 puffs solution for inhalation Respimat
  Intervention: Drug: tiotropium + olodaterol
• Active Comparator: olodaterol
  Once daily 2 puffs solution for inhalation Respimat
  Intervention: Drug: olodaterol
• Active Comparator: tiotropium low dose
  Once daily 2 puffs solution for inhalation Respimat
  Intervention: Drug: tiotropium
• Active Comparator: tiotropium high dose
  Once daily 2 puffs solution for inhalation Respimat
  Intervention: Drug: tiotropium

Inclusion criteria:

1. Diagnosis of chronic obstructive pulmonary disease.
2. Relatively stable airway obstruction with post FEV1< 80% predicted normal and post FEV1/FVC <70%.
3. Male or female patients, 40 years of age or older.
4. Smoking history of more than 10 pack years.

Exclusion criteria:

1. Significant disease other than COPD
2. Clinically relevant abnormal lab values.
3. History of asthma.
4. Diagnosis of thyrotoxicosis
5. Diagnosis of paroxysmal tachycardia
6. History of myocardial infarction within 1 year of screening visit
7. Unstable or life-threatening cardiac arrhythmia.
8. Hospitalization for heart failure within the past year.
9. Known active tuberculosis.
10. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
11. History of life-threatening pulmonary obstruction.
12. History of cystic fibrosis.
13. Clinically evident bronchiectasis.
14. History of significant alcohol or drug abuse.
15. Thoracotomy with pulmonary resection
16. Oral ß-adrenergics.
17. Oral corticosteroid medication at unstable doses
18. Regular use of daytime oxygen therapy for more than one hour per day
19. Pulmonary rehabilitation program in the six weeks prior to the screening visit
20. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
21. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
22. Pregnant or nursing women.
23. Women of childbearing potential not using a highly effective method of birth control
24. Patients who are unable to comply with pulmonary medication restrictions