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

Study Overview
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Brief Summary
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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

Official Title
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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)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Ipratropium bromide HFA-134a inhalation aerosol
* Drug: Atrovent® CFC inhalation aerosol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipratropium bromide HFA-134a low<br> | Drug: Ipratropium bromide HFA-134a inhalation aerosol<br> <br> |
| Experimental: Ipratropium bromide HFA-134a high<br> | Drug: Ipratropium bromide HFA-134a inhalation aerosol<br> <br> |
| Active Comparator: Atrovent® CFC low<br> | Drug: Atrovent® CFC inhalation aerosol<br> <br> |
| Active Comparator: Atrovent® CFC high<br> | Drug: Atrovent® CFC inhalation aerosol<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced expiratory volume in 1 second (FEV1) response, calculated as area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 (AUC0-6) |  | After each drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in peak FEV1 response |  | Baseline and after each drug administration | 
| Onset of therapeutic FEV1 response |  | After each drug administration | 
| Duration of therapeutic FEV1 response |  | After each drug administration | 
| Time to peak FEV1 response |  | After each drug administration | 
| Forced Vital Capacity (FVC) AUC0-6 |  | After each drug administration | 
| Changes from baseline in FEV1 |  | Baseline and after each drug administration | 
| Number of patients with adverse events |  | Up to 5 month after first drug administration | 
| Peak FVC response |  | After each drug administration | 
| Changes from baseline in FVC |  | Baseline and after each drug administration |