Trial to Determine the Comparability of Ipratropium Bromide Hydrofluoroalkane (HFA)-134a Inhalation Aerosol to ATROVENT® Chlorofluorocarbon (CFC) Inhalation Aerosol, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

An Open-Label, Crossover, Pharmacokinetic Trial to Determine the Comparability of 84 µg Ipratropium Bromide HFA-134a Inhalation Aerosol to 84 µg ATROVENT® CFC Inhalation Aerosol, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

The objective of this study was to determine the pharmacokinetic comparability of 84 µg ipratropium bromide HFA-134a inhalation aerosol and 84 µg ATROVENT® CFC Inhalation Aerosol in COPD patients

Inclusion Criteria:

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

• Patients must have a stable, moderate to severe airway obstruction with an Forced Expiratory Volume in one second (FEV1) <=65% of predicted normal and FEV1 <=70% of Forced vital capacity (FVC)

  • Males: Predicted Normal FEV1 = 0.093 (height in inches)-0.032 (age)-1.343
  • Females: Predicted Normal FEV1 = 0.085 (height in inches)-0.025(age)-1.692

• Male or female age 40 years 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 cigarettes (20 cigarettes) per day for a year

• Patients must be able to satisfactorily administer the medication, perform pulmonary function tests (PFTs) and maintain records during the study period as required in the protocol

• 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 and prior to fasting for laboratory tests)

Exclusion Criteria:

• Patients with significant diseases 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 with may influence the results of the study or patients ability to participate in the study
• Patients with clinically relevant 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 (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 the clinical condition. Repeat laboratory evaluation will be not be conducted in these patients
• Patients with a history of asthma, allergic rhinitis or atopy or who have a blood eosinophil count above 600/mm3. A repeat eosinophil count will be not be conducted in these patients
• Patients with a recent (i.e., one year or less) history of myocardial infarction
• Patients with a recent history (i.e., three years or less) of cardiac failure, patients with cardiac arrhythmia requiring therapy, patients receiving any systemic beta-blockers and patients on chronic daytime oxygen therapy
• Patients with known active tuberculosis
• Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma are allowed
• 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 an upper respiratory tract infection or COPD exacerbation in the 6 weeks prior to the screening visit (Visit 1) or during the baseline period
• Patients with known hypersensitivity to anticholinergic drugs
• Patients with known symptomatic prostatic hypertrophy or bladder-neck obstruction
• Patients with known narrow-angle glaucoma
• Patients who are on cromolyn sodium or nedocromil sodium
• Patients who are on antihistamines
• Pregnant or nursing women and women of childbearing potential not using a medically approved means of contraception (e.g., oral contraceptive, intrauterine devices, diaphragm or Norplant®)
• Patients who have taken an investigational drug within 1 month or 6 half-lives (whichever is longer) of the drug prior to the screening visit or patients currently enrolled in another research study
• Patients with a history of and/or active alcohol or drug abuse