To compare the long-term (one-year) bronchodilator efficacy and safety of COMBIVENT hydrofluoroalkane (HFA) Inhalation Aerosol to COMBIVENT chlorofluorocarbon (CFC) Inhalation Aerosol and Placebo formulations of each in patients with COPD. In addition, steady state pharmacokinetics over one dosing interval following four weeks of therapy will be characterized.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
360
Area under the curve from 0 to 6 hours (AUC0-6) of forced expiratory volume in the first second (FEV1)
Time frame: after 12 weeks
Peak FEV1 response
Time frame: 28 weeks
Onset of therapeutic FEV1 response
Time frame: 28 weeks
Duration of therapeutic FEV1 response
Time frame: 28 weeks
Time to peak FEV1 response
Time frame: 28 weeks
Average FEV1 response as area under the curve from 0 - 6 hours divided by six (TAUC0-6)
Time frame: 28 weeks
Average forced vital capacity (FVC) response area under the curve from 0 - 6 hours divided by six (AUC0-6)
Time frame: 28 weeks
Number of participants requiring test-day rescue therapy
Time frame: 28 weeks
Peak expiratory flow rate (PEFR)
Time frame: 28 weeks
Daily COPD symptom scores
Time frame: 28 weeks
Number of puffs of rescue medication
Time frame: 28 weeks
Number and length of COPD exacerbations
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Time frame: 28 weeks
Average FEV1 response as area under the curve from 0 - 8 hours divided by six (TAUC0-8)
Time frame: 28 weeks
Number of adverse events including paradoxical bronchoconstrictions
Time frame: 28 weeks
Number of patients with clinically significant changes in pulse rate and blood pressure
Time frame: 28 weeks
Plasma ipratropium concentration
Time frame: pre-treatment, 5, 15, 30 min; 1, 2, 4 and 8 hours
Plasma albuterol concentration
Time frame: pre-treatment, 5, 15, 30 min; 1, 2, 4 and 8 hours
Renal excretion of ipratropium fractions
Time frame: pre-treatment, 0 - 2 hours, 2 - 8 hours
Renal excretion of albuterol fractions
Time frame: pre-treatment, 0 - 2 hours, 2 - 8 hours
Physician's global evaluation on an 8-point scale
Time frame: 28 weeks
Peak FVC response
Time frame: 28 weeks
Number of patients with clinically significant changes in laboratory tests
Time frame: 28 weeks
Number of patients with abnormal findings in physical examination
Time frame: 28 weeks
Number of patients with clinically significant changes in electrocardiogram
Time frame: 28 weeks