Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Exclusion Criteria

• •1. History of asthma, allergic rhinitis or atopy or who have a blood eosinophil count above 600/mm³
• •2. Changes in the therapeutic (pulmonary) plan within the last six weeks prior to the Screening Visit;
• •3. Treatment by cromolyn/nedocromil sodium;
• •4. Treatment by antihistamines (H1 receptor antagonists);
• •5. A lower respiratory tract infection or any exacerbation in the past six weeks prior to the Screening Visit;
• •6. Regular use of daytime oxygen therapy;
• •7. Treatment by oral corticosteroid medication if initiated or modified within the last six weeks or if daily dose \> 10 mg prednisone equivalent;
• •8. History of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis
• •9. Patients who have undergone thoracotomy with pulmonary resection;
• •10. History of clinically significant cardiovascular, renal neurologic, liver or endocrine dysfunction. A clinically significant disease was defined as one which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.
• •11. Patients with a recent (≤ one year) history of myocardial infarction, of heart failure or patients with any cardiac arrhythmia requiring drug therapy;
• •12. Tuberculosis with indication for treatment;
• •13. History of cancer within the last five years. Patients with treated basal cell carcinoma were allowed:
• •14. Current psychiatric disorders;
• •15. Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction;
• •16. Patients with any history of glaucoma or increased intra-ocular pressure;
• •17. Patients with clinically significant abnormal baseline haematology or blood chemistry, if the abnormality defines a disease listed as an exclusion criterion;
• •18. Patients with
• •1. glutamyl-oxalo-acetic transaminase/glutamyl-pyruvic transaminase (SGOT/SGPT): \> 200% of the upper limit of the normal range (ULN, )
• •2. bilirubin: \> 150% of the ULN,
• •3. creatinine: \> 125% of the ULN;
• •19. Intolerance to aerosolised anticholinergic containing products, and/or hypersensitivity to benzalkonium chloride, to lactose or any other components of the inhalation capsule delivery system;
• •20. Beta-blocker medication;
• •21. Concomitant or recent (within the last month) use of investigational drugs;
• •22. History of drug abuse and/or alcoholism;
• •23. Pregnant or nursing women and women of childbearing potential not using a medically approved means of contraception ( urinary pregnancy test at screening);
• •24. Previous participation in this study (i.e. having been allocated a randomised treatment number);
• •25. Patients deprived of their freedom by a judicial or administrative decision;
• •26. Minors, adults under guardianship;
• •27. Persons in medical or social establishments;
• •28. Patients in emergency situations