Comparison of Safety and Efficacy of COMBIVENT HFA to COMBIVENT (CFC) in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Comparison of Safety and Efficacy of COMBIVENT HFA to COMBIVENT (CFC) in Patients With Chronic Obstructive Pulmonary Disease (COPD)
To compare the long-term (one-year) bronchodilator efficacy and safety of COMBIVENT
 hydrofluoroalkane (HFA) Inhalation Aerosol to COMBIVENT chlorofluorocarbon (CFC) Inhalation
 Aerosol and Placebo formulations of each in patients with COPD. In addition, steady state
 pharmacokinetics over one dosing interval following four weeks of therapy will be
 characterized.
Inclusion Criteria:

 -  All patients must have a diagnosis of COPD

 -  Male or female patients 40 years of age or older

 -  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 20 cigarettes per day for a year

 -  Patients must be able to perform technically satisfactory pulmonary function tests

 -  Patients must be able to be trained in the proper use of a metered dose inhalator
 (MDI)

 -  All patients must sign an Informed Consent Form prior to participation in the trial
 i.e. prior to pre-study washout of their usual pulmonary medications

 -  Patients must be on at least one regular aerosol bronchodilator for control of their
 COPD symptoms and have symptoms of bronchospasm (wheeze or shortness of breath)
 present OR Patients must be on at least two classes of prescribed bronchodilators on a
 regular basis for control of their COPD symptoms for the three month period
 immediately preceding the screening visit.

 Exclusion Criteria:

 -  Patients with significant disease 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 relevant abnormal baseline hematology, blood chemistry or
 urinalysis. If the abnormality defines a disease listed as an exclusion criterion, the
 patient is excluded

 -  All patients with a serum aspartate amino transferase (ASAT/SGOT) > 80 IU/L, serum
 alanine amino transferase (ALAT/SGPT) > 80 IU/L, bilirubin > 2.0 mg/dL or creatinine >
 2.0 mg/dL will be excluded regardless of the clinical condition. Repeat laboratory
 evaluation will not be conducted in these patients.

 -  Patients who have a total bood eosinophil count >= 600 mm**3. A repeat eosinophil
 count will not be conducted in these patients

 -  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 or patients
 with any cardiac arrhythmia requiring drug therapy

 -  Patients with a history of cancer, other than treated basal cell carcinoma, within the
 last five years

 -  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 wth a
 history of thoracotomy for other reasons should be evaluated as per exclusion
 criterion No. 1

 -  Patients with a history of asthma, allergic rhinitis or atopy.

 -  Patients with a history of or active alcohol or drug abuse

 -  Patients with known active tuberculosis

 -  Patients with an upper respiratory tract infection or COPD exacerbation in the six
 weeks prior to the Screening Visit (Visit 1) or during the baseline period

 -  Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction

 -  Patients with known narrow-angle glaucoma

 -  Patients with current significant psychiatric disorders

 -  Patients with regular use of daytime oxygen therapy

 -  Patients who are being treated with beta-blocker medications, monoamine oxidase (MAO)
 inhibitors or tricyclic antidepressants

 -  Patients who are being treated with cromolyn sodium or nedocromil sodium

 -  Patients who are being treated with antihistamines

 -  Patients using oral corticosteroid medication at unstable doses or at a dose in excess
 of the equivalent of 10 mg of prednisone per day or 20 mg every other day

 -  Patients who have been treated with oral beta-adrenergics or long-acting
 beta-adrenergics in the two weeks prior to the Screening Visit or during the baseline
 period

 -  Patients who have had changes in their therapeutic plan within the last six weeks
 prior to the Screening Visit or during the baseline period, excluding changes from
 long acting or oral beta-adrenergics to short acting inhaled beta-adrenergics for
 purposes of this trial

 -  Pregnant of nursing women or woman of childbearing potential not using a medically
 approved means of contraception

 -  Patients with known hypersensitivity to anticholinergic or beta-agonist drugs or any
 other component of either COMBIVENT formulation

 -  Patients who have taken an investigational drug within one month or six half lives
 (whichever is greater) prior to Screening visit

 -  Previous participation in this study