Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)

A Multiple Dose Comparison of Tiotropium Inhalation Capsules, Salmeterol Inhalation Aerosol and Placebo in a Six-Month, Double-Blind, Double-Dummy, Safety and Efficacy Study in Patients With Chronic Obstructive Pulmonary Disease (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