Tiotropium / Respimat One-Year Study

• Change From Baseline in Trough FEV1 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT) [ Time Frame: Baseline to Week 48 ]
  Trough Forced Expiratory Volume in 1 second (FEV1)
• Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL) [ Time Frame: Week 48 ]
  Rating scale of 3 domains - symptoms, activities and impact (weighted). Worst score = 100, best score = 0
• TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) [ Time Frame: Week 48 ]
  Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9
• COPD Exacerbation Rate, Safety Set (SS) [ Time Frame: 48 weeks ]
  Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year

• Change From Baseline in Heart Rate [ Time Frame: Baseline to Week 40 pre-dose ]
  Week 40 pre-dose - baseline
• Change From Baseline in PR Interval [ Time Frame: Baseline to Week 40 pre-dose ]
• Change From Baseline in QRS Interval [ Time Frame: Baseline to Week 40 pre-dose ]
  Week 40 pre-dose - baseline
• Change From Baseline in QT Interval [ Time Frame: Baseline to Week 40 pre-dose ]
  Week 40 pre-dose - baseline
• Change From Baseline in QT Interval (Bazett) [ Time Frame: Baseline to Week 40 pre-dose ]
  Week 40 pre-dose - baseline
• Change From Baseline in QT Interval (Fridericia) [ Time Frame: Baseline to Week 40 pre-dose ]
  Week 40 pre-dose - baseline
• Change From Baseline in Heart Rate [ Time Frame: Baseline to Week 40 ]
  Week 40 - baseline
• Change From Baseline in Supraventricular Premature Beat (SVPB) Total [ Time Frame: Baseline to Week 40 ]
  Week 40 - baseline
• Change From Baseline in SVPB Run Events [ Time Frame: Baseline to Week 40 ]
  Week 40 - baseline
• Change From Baseline in SVPB Pairs [ Time Frame: Baseline to Week 40 ]
  Week 40 - baseline
• Change From Baseline in Ventricular Premature Beat (VPB) Total [ Time Frame: Baseline to Week 40 ]
  Week 40 - baseline
• Change From Baseline in Ventricular Premature Beat (VPB) Run Events [ Time Frame: Baseline to Week 40 ]
  Week 40 - baseline
• Change From Baseline in VPB Pairs [ Time Frame: Baseline to Week 40 ]
  Week 40 - baseline
• Change From Baseline in Haematocrit, Packed Cell Volume (PCV) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
• Change From Baseline in Haemoglobin [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Red Blood Cell Count [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in White Blood Cell Count [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Platelets [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Neutrophils [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Eosinophils [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Basophils [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Lymphocytes [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Monocytes [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Neutrophils (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Eosinophils (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Basophils (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Lymphocytes (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Monocytes (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Calcium [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Phosphate [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Aspartate Transaminase/Glutamic-oxaloacetic Transaminase (AST/GOT), Serum Glutamic-oxaloacetic Transaminase (SGOT) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Alanine Transaminase/Glutamic Pyruvate Transaminase (ALT/GPT), Serum Glutamate Pyruvate Transaminase (SGPT) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Alkaline Phosphatase [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Lactic Dehyrogenase (LDH) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Glucose [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Urea [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Blood Urea Nitrogen [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Creatinine [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Bilirubin, Total [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Uric Acid [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Protein, Total [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline
• Change From Baseline in Albumin [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ]
  Week 48 - baseline

To evaluate the long term effects of treatment with two doses of Tiotropium delivered by the Respimat inhaler in patients with COPD.

• Drug: Tiotropium Inhalation Solution
• Other: Placebo

• Tiotropium Respimat 5mcg (Tio R5)
  Intervention: Drug: Tiotropium Inhalation Solution
• Tiotropium Respimat 10mcg (Tio R10)
  Intervention: Drug: Tiotropium Inhalation Solution
• Placebo
  Intervention: Other: Placebo

Criteria

• Patients with stable moderate to severe COPD and a smoking history of at least 10 pack years were eligible for inclusion in the study. Patients with significant diseases other than COPD were excluded as were patients with a recent history of myocardial infarction, history of malignancy, unstable or life-threatening cardiac arrhythmia, narrow-angle glaucoma, asthma or other allergic conditions. Patients treated with cromolyn, nedocromil, oral beta-adrenergics or unstable doses of oral corticosteroids were ineligible for inclusion in the study as were patients who had received previous treatment with tiotropium.