Study of the Comparability of Ipratropium Bromide Hydrofluoroalkane (HFA)-134a Inhalation Aerosol to the Market Standard, Atrovent® Chlorofluorocarbon (CFC) Inhalation Aerosol, in Patients With Chronic Obstructive Pulmonary Disease

A Single-Dose, Double Blind, Crossover Trial to Determinate the Comparability of Ipratropium Bromide HFA-134a Inhalation Aerosol to the Market Standard, Atrovent® CFC Inhalation Aerosol, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

The objective of this study was to compare the bronchodilator efficacy and safety of ipratropium bromide HFA-134a inhalation aerosol and marketed, 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 stable, moderate to severe airway obstruction with an FEV 1 (forced expiratory volume in the first second) <=65% of predicted normal and FEV1 <=70% of FVC (Forced Vital Capacity)

  • 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 patients 40 years of age or older

• Patients must have a smoking history of more than ten pack-years

• Patients must be able to demonstrate an improvement in FEV1 >=015% within one hour after inhalation of two puffs of Atrovent® inhalation aerosol (21 mcg per puff)

• Patients must be able to satisfactorily administer the medication, perform pulmonary function test 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 disease other than COPD were 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 clinical 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 not to be conducted in these patients
• Patients with a history of asthma, allergic rhinitis or atopy or have a blood eosinophil count above 600/mm³. A repeat eosinophil count will not to 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, patients with any cardiac arrhythmia requiring therapy, patients receiving any systemic beta blocker and patients on chronic daytime oxygen therapy
• Patients with known active tuberculosis
• Patients with a history of cancer within the last five 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 or a thoracotomy for other reasons be evaluated as per exclusion criterion No. 1
• Patients with an upper respiratory tract infection or COPD exacerbation in the six weeks prior to screening visit (vist1) 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 or women of childbearing potential not using a medically approved means of contraception (e.g., oral contraceptives, intrauterine devices, diaphragm or Norplant®)
• Patients who have taken an investigational drug within one month or 6 half-lives (whichever is longer) of the drug prior to the screening visit or patients currently enrolled in other research study
• Patients with a history of and/or active alcohol or drug abuse

Exclusion criteria for patients with allergies

• Patients with active infectious rhinitis (common cold) as determined by history and physical
• Patients with upper or lower respiratory infection at screening