Comparison of Safety and Efficacy of Berodual® Administered Via the Respimat® Device With That Administered Via the Metered Dose Inhaler (MDI) in Patients With Chronic Obstructive Pulmonary Disease (COPD)

A Randomized, Placebo-controlled, Within-device, Double-blind Tri-national Study to Compare the Safety and Efficacy of Berodual® Administered Via the Respimat® Device (50 µg Fenoterol Hydrobromide/20 µg Ipratropium Bromide and 25 µg Fenoterol Hydrobromide/10 µg Ipratropium Bromide, 1 Puff q.i.d) With That Administered Via the MDI (50 µg Fenoterol Hydrobromide/21 µg Ipratropium Bromide, 2 Puffs q.i.d) in COPD Patients Over a 12-week Period

To demonstrate that at least one of the two doses of Berodual® (50 µg fenoterol hydrobromide/20 µg ipratropium bromide and 25 µg fenoterol hydrobromide/10 µg ipratropium bromide, 1 puff q.i.d) administered via the Respimat® gives a bronchodilator response which is not inferior to that obtained from one dose of Berodual® (50 µg fenoterol hydrobromide/21 µg ipratropium bromide, 2 puffs q.i.d) administered via the MDI and that the safety profile is at least as good when COPD patients are treated for 12 weeks.

Inclusion Criteria:

• Age >= 40 years

• Diagnosis of COPD according the following criteria:

  • screening FEV1<= 65% predicted
  • Screening FEV1/FVC <= 70%

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

• Able to be trained in the proper use of MDI and Respimat®

• Able to be trained in the performance of technically satisfactory pulmonary function tests

• All patients must be willing and able to sign informed consent in accordance with Good clinical Practice (GCP) and local legislation

Exclusion Criteria:

• History of cardiovascular, renal, neurologic, liver or endocrine dysfunction (e.g. hyperthyreosis) if they are clinically significant. A clinically significant disease is 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 or the study or the patient's ability to participate in the study

• Patients with a recent (<= one year) history of myocardial infarction

• Tuberculosis with indication for treatment

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

• Patients who have undergone thoracotomy

• Current psychiatric disorders

• History of life-threatening pulmonary obstruction, cystic fibrosis or bronchiectasis

• An upper and lower respiratory tract infection in the four weeks prior to the screening visit

• Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction

• Patients with known narrow-angle glaucoma or raised intra-ocular pressure

• Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion

• Patients with:

  • Serum glutamic oxalo-acetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) >200% of the upper limit of the normal range
  • Bilirubin >150% of the upper limit of the normal range
  • Creatinine >125% of the upper limit of the normal range

• Patients who are on chronic oxygen therapy

• Intolerance to aerosolised ipratropium- or fenoterol-containing products, or hypersensitivity to any of the MDI ingredients

• Oral corticosteroid mediation at dose greater than 10 mg prednisolone per day or equivalent

• Beta-blocker medication

• Changes in the pulmonary therapeutic plan within the last four weeks prior to the screening visit (not including withholding of medication before the screening visit)

• Concomitant or recent (within the last month) use of investigational drugs

• History of drug abuse and/or alcoholism

• Pregnant or nursing women and women of child-bearing potential not using a medically approved means of contraception

• Previous participation in this study (i.e. having been allocated a randomized treatment number)

• Patients with a history of asthma, allergic rhinitis or atopy or who have blood eosinophil count above 600/mm3 (a repeat eosinophil count will not be conducted in these patients) and those patients on antihistamines, anti-leukotrienes, sodium cromoglycate or nedocromil sodium

• Patients who are unable to comply with the medication restrictions specified in section 4.2 or who cannot use an MDI without a spacer