Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
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
Interventions
DRUGAtrovent CFC inhalation aerosol
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Amount of unchanged ipratropium excreted in the urine from 0 to 24 h after a single dose | Up to 24 hours (h) after single drug administration |
| Amount of unchanged ipratropium excreted in the urine within 1 hour at steady state | 1h after drug administration |
| Amount of unchanged ipratropium excreted in the urine over the 6 h dosing interval at steady state | up to 6 h after drug administration |
Secondary
| Measure | Time frame |
|---|---|
| Trough plasma ipratropium concentration at different time points | Up to 23 days after first drug administration |
| Time to peak plasma ipratropium concentrations at steady state | Up to 23 days after first drug administration |
| Degree of fluctuation (DF) of the plasma ipratropium concentrations | Up to 23 days after first drug administration |
| Area under the plasma ipratropium concentration time curve | Day 1 after first drug administration |
| Peak plasma ipratropium concentration | Day 1 after first drug administration |
| Number of patients with clinical significant findings in laboratory tests | Up to 23 days after first drug administration |
| Changes from baseline in pulse rate and blood pressure | Baseline, day 23 day after first drug administration |
| Number of patients with clinical significant findings in physical examination | Up to 23 days after first drug administration |
| Number of patients with clinical significant findings in electrocardiogram (ECG) | Up to 23 days after first drug administration |
| Changes from test-day baseline in pulse rate and blood pressure | Up to 23 days after first drug administration |
| Number of patients with adverse events | Up to 23 days after first drug administration |
| Area under the plasma ipratropium concentration time curve at different time points | Up to 23 days after first drug administration |
| Peak plasma ipratropium concentration at different time points | Up to 23 days after first drug administration |
Outcome results
None listed