Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD

Inclusion Criteria

• The patient has signed an Informed Consent Form in accordance with GCP and local legislative requirements prior to participation in the trial, i.e., prior to pre-trial washout of any restricted medications.
• The patient has a clinical diagnosis of chronic obstructive pulmonary disease (COPD).
• The patient has relatively stable, moderate to severe airway obstruction.
• The patient has a pre-bronchodilator forced expiratory volume in the first second (FEV1) less than or equal to 65% of predicted normal determined at Visit 1 using the following predicted equations (R94-1408):
• Males Forced expiratory volume in the first second (FEV1) predicted [Litres (L)] = 4.30 x Height [metres] minus 0.029 x Age [years] minus 2.49
• Females Forced expiratory volume in the first second (FEV1) predicted [Litres (L)] = 3.95 x Height [metres] minus 0.025 x Age [years] minus 2.60 and a Thoracic Gas Volume (Functional residual volume) ((TGV)(FRC)) bigger than 120% predicted normal at visit 1 (or historical data not older than 6 month)
• Males Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. [Litres (L)] = 2.34 x Height [metres] + 0.009 x Age [years] minus 1.09
• Females Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. [Litres (L)] = 2.24 x Height [metres] + 0.001 x Age [years] minus 1.00
• The patient is at least 40 years and less than or equal to 75 years old.
• The patient has a cigarette smoking history of at least 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year.
• The patient is able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol.
• The patient is able to inhale the trial medication from the HandiHaler device.
• The patient is able to inhale the trial medication from the Diskus/Accuhaler device.

Exclusion Criteria

• a significant disease other than chronic obstructive pulmonary disease (COPD). (review contraindications for exercise testing),
• a recent history of myocardial infarction within one year.
• a recent history of heart failure, pulmonary oedema, or patients with cardiac arrhythmia or any contraindication to exercise described in the CTProtocol within the last 3.
• daytime supplemental oxygen.
• a diagnosis of known active tuberculosis.
• a history of cancer within the last 5 years.
• a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
• thoracotomy with pulmonary resection.
• an upper respiratory tract infection or an exacerbation of chronic obstructive pulmonary disease (COPD)
• a known hypersensitivity to anticholinergic drug, ß-adrenergic or corticosteroids, lactose or any other component of the inhalation capsule delivery system.
• a known symptomatic prostatic hypertrophy or bladder neck obstruction.
• a known moderate or severe renal insufficiency.
• a known narrow-angle glaucoma.
• a known untreated hypokalemia.
• a known untreated thyrotoxicosis.
• a history of asthma, allergic rhinitis or atopy, or a total blood eosinophil count larger than 600/mm3.
• treatment with cromolyn sodium or nedocromil sodium
• treatment with antihistamines or antileukotrienes.
• treatment with tiotropium for 1 month before Visit 1.
• treatment with oral corticosteroid medication.
• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
• a history of or active alcohol or drug abuse.
• an investigational drug within 1 month or 10 half lives
• a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea.
• participation in a rehabilitation program for chronic obstructive pulmonary disease (COPD).
• treatment with monoamine oxidase inhibitors inhibitors or tricyclic antidepressants.
• participation in another study.
• more than eight pu