Study to Assess the Safety of Ipratropium Bromide, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

A Double-blind, Placebo Controlled Trial to Assess the Safety of Two-week Administration of 80 mcg q.i.d. and 160 mcg q.i.d. of Ipratropium Bromide, as Delivered by the RESPIMAT® Device, in Patients With Chronic Obstructive Pulmonary Disease

Study to assess the safety of two-week administration of 80 and 160 mcg of ipratropium bromide as delivered by the RESPIMAT® device and as determined by 24 hours ambulatory ECG monitoring in COPD patients. To assess the overall safety of the two doses of ipratropium bromide as delivered by the RESPIMAT® device when administered over a two-week period.

Inclusion Criteria:

All patients must have a diagnosis of COPD and must meet the following spirometric criteria:

• Patients must have relatively stable, moderate to severe airway obstruction with an FEV1 <=65% of predicted normal and FEV1 <=70% of forced vital capacity (FVC). Predicted normal value will be calculated according to Morris

  • Males: FEV1 = 0.093 (Height in inches)-0.032 (age)-1.343
  • Females: FEV1 = 0.085 (Height. in inches)-0.025(age)-1.692

• Male or female patients 40 years of age or older

• Patients must have a smoking history of more than 10 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 pulmonary function tests (PFTs) and maintain records during the study period as required in the protocol

• Patients must be able to be trained in the proper use of an inhalation aerosol and the RESPIMAT™ device

• Patients must have a baseline electrocardiogram (ECG) with no clinical relevant arrhythmias or conduction system disease (e.g. right or left bundle branch block, second degree AV block or higher)

• Patients must have an oxygen saturation of >=90% for >=92% of the recording time on overnight oximetry

• All patients must sign an Informed Consent Form prior to participation in the trial (i.e., at least 24 hours (h) prior to the screening visit (Visit 1))

Exclusion Criteria:

• Patients with clinically relevant diseases other than COPD will be excluded. A clinically relevant 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 with may influence the results of the study or patient's ability to participate in the study
• Patients with a recent history (i.e. one year or less) of myocardial infarction
• Patients with a recent history (i.e. one year or less) of heart failure or patients with any past history or active cardiac arrhythmia requiring drug therapy
• Patients who have a pacemaker
• 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 serum glutamic oxaloacetic transaminase / Aspartate aminotransferase (SGOT/AST) >80 IU/L, serum glutamic pyruvic transaminase / Alanine transaminase (SGPT/ALT) >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 be not be conducted in these subjects
• Patients who have a blood eosinophil count >=600/mm3. A Repeat eosinophil count will be not be conducted in these patients
• Patients with a history of cancer, other than treated basal cell carcinoma, within the last 5 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 with a history of thoracotomy for other reason should be evaluated per exclusion criterion No. 1
• Patients with a history of asthma, allergic rhinitis or atopy
• Patients with a history of and/or active alcohol or drug abuse
• Patients with known active tuberculosis
• Patients with an upper respiratory tract infection or COPD exacerbation in the past 6 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 cromolyn sodium or nedocromil sodium
• Patients who are being treated with antihistamines
• 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
• Patients who are being treated with beta-blocker medication
• Patients who have had changes in their therapeutic plan within the last six weeks prior to the screening visit (visit 1)
• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (e.g., oral contraceptive, intrauterine devices, diaphragm or Norplant®)
• Patients with known hypersensitivity to ant cholinergic drugs or any other components of the ATROVENT® RESPIMAT™ solution including bacteriostatic agent benzalkonium chlorid (BAC) and edetic acid (EDTA)
• Patients who have taken an investigational drug within 1 month or 6 half-lives (whichever is longer) prior to the screening visit (visit1)
• Previous participation in this study