Effect of Tiotropium on Airway Diameter in Patients With Chronic Obstructive Pulmonary Disease (COPD)

The Effects of Tiotropium Therapy on Airway Diameter in Patients With COPD (a Randomized, Double-blind, Placebo-controlled, Parallel-group Study)

Trial to investigate the acute and chronic effect of tiotropium therapy on airway diameter in COPD patients as measured by inspiratory capacity (IC).

Inclusion Criteria:

• All patients must have a diagnosis of chronic obstructive pulmonary disease
• Male or female patients ≥ 40 years of age but ≤ 75 years old
• Patients must have a smoking history of more than ten pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year
• Patients must be able to perform all specified procedures and maintain records during the study period as required in the protocol
• Patients must be able to inhale medication from the HandiHaler®
• All patients must sign a Patient Informed Consent Form prior to participation in the trial i.e., prior to pre-study washout of their usual pulmonary medications
• Patients must be willing to attend an outpatient clinic on a regular basis
• Patients must be able to walk 164 feet (50 meters) during the Six Minute Walk Test

Exclusion Criteria:

• Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease 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
• Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis test results, if the abnormality defines a disease listed as an exclusion criterion
• Patients with a serum glutamic-oxaloacetic transaminase (SGOT) ≥1.5 x Upper Limit of Normal Range (ULN), serum glutamic-pyruvic transaminase (SGPT) ≥1.5 x ULN, bilirubin ≥1.5 x ULN or creatinine ≥ 1.5 x ULN regardless of the clinical condition
• Patients with a recent history (i.e., one year or less) of myocardial infarction
• Patients with a recent history (i.e., three years or less) of heart failure, pulmonary edema or patients with any cardiac arrhythmia (with or without symptoms)
• Patients with regular use of daytime oxygen therapy
• Patients with known active tuberculosis
• Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed
• Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis
• Patients who have undergone thoracotomy with pulmonary resection. Patients with a history or a thoracotomy for other reason should be evaluated as per exclusion criterion no. 1
• Patients with upper respiratory tract infection in the past six weeks prior to the Screening Visit or during the baseline period
• Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system
• Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction
• Patients with known narrow-angle glaucoma
• Patients who are being treated with cromolyn sodium or nedocromil sodium
• Patients who are being treated with antihistamines (H1 receptor antagonists) or antileukotrienes and are not able to stop these medications 1 month before visit 1
• Patients using oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day
• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
• Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count ≥ 600/mm3
• Patients with history of (past five years or less) and/or active alcohol or drug abuse
• Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Period (Visit 1)
• Patients who have participated in any pulmonary rehabilitation program for COPD within 6 weeks prior to Visit 1 or throughout the study
• Limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea such as arthritis in the leg, angina or claudication