Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)
Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)
The objective of this study is to compare the long-term (six month) bronchodilator efficacy
 and safety of tiotropium inhalation capsules, salmeterol inhalation aerosol and placebo
 inpatients with COPD.
Inclusion Criteria:

 -  Age ≥ 40 years.

 -  A diagnosis of relatively stable, moderate to severe COPD with:

 -  Screening FEV1 ≤ 60% of predicted normal value (calculated according to European
 Community for Coal and Steel (ECCS) criteria and screening FEV1/FVC ≤ 70%

 -  Smoking history ≥ 10 pack-years (a pack-year is 20 cigarettes per day for one year or
 equivalent)

 -  Ability to be trained in the proper use of the HandiHaler® device and Metered Dose
 Inhaler (MDI).

 -  Ability to perform all study related tests including the Shuttle Walking Test,
 acceptable pulmonary function tests, including Peak expiratory flow rate (PEFR)
 measurements, and maintenance of diary card records.

 -  Ability to give written informed consent in accordance with Good Clinical Practice and
 local regulations.

 Exclusion Criteria:

 -  Clinically significant diseases other than COPD.

 -  Patients with clinically relevant abnormal baseline haematology, blood chemistry or
 urinalysis, if the abnormality defines a disease listed as an exclusion criterion,
 will be excluded.

 -  All patients with a serum glutamic oxaloacetic transaminase (SGOT) > 80 IU/L, serum
 glutamic pyruvic transaminase (SGPT) > 80 IU/L, bilirubin >2.0 mg/dL or creatinine >
 2.0 mg/dL will be excluded regardless of clinical condition.

 -  A recent history (i.e., one year or less) of myocardial infarction.

 -  Any cardiac arrhythmia requiring drug therapy or hospitalisation for heart failure
 within the past three years.

 -  Inability to abstain from regular daytime use of oxygen therapy for more than 1 hour
 per day.

 -  Known active tuberculosis.

 -  History of cancer within the last five years (excluding basal cell carcinoma)

 -  History of life-threatening pulmonary obstruction, or a history of cystic fibrosis or
 bronchiectasis.

 -  Patients who have undergone thoracotomy with pulmonary resection.

 -  Any upper respiratory infection in the past six weeks prior to the screening visit or
 during the run-in period.

 -  Current participation in a pulmonary rehabilitation programme or completion of a
 pulmonary rehabilitation programme in the six week prior to the screening visit.

 -  Known hypersensitivity to anticholinergic drugs, salmeterol, or any of the components
 of the lactose powder capsule or MDI delivery systems.

 -  Known symptomatic prostatic hypertrophy or bladder neck obstruction.

 -  Patients with known narrow-angle glaucoma.

 -  Current treatment with cromolyn sodium or nedocromil sodium.

 -  Current treatment with antihistamines (H1 receptor antagonists).

 -  Oral corticosteroid medication at unstable doses (i.e., less than six weeks on a
 stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day
 or 20 mg every other day.

 -  Current use of β-blocker medication.

 -  Current treatment with monoamine oxidase inhibitors or tricyclic antidepressants.

 -  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 > 600mm3.

 -  History of and/or active significant alcohol or drug abuse.

 -  Concomitant or recent use of an investigational drug within one month or six half
 lives (whichever is greater) prior to the screening visit.

 -  Changes in the pulmonary therapeutic plan within the six weeks prior to the screening
 visit.

 -  Inability to comply with the medication restrictions specified in Section 4.2 of the
 trial protocol