Combivent® HFA-propelled Compared to CFC-propelled Metered Dose Inhaler in Patients With COPD (Chronic Obstructive Pulmonary Disease)

Study Overview
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Brief Summary
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Study to evaluate the safety of combivent delivered in two different formulations (hydrofluoroalkane (HFA) or chlorofluorocarbon (CFC)) from a metered dose inhaler (MDI), using a cumulative dose response model in patients with COPD.

Official Title
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Safety Assessment of Cumulative Dose of Combivent® HFA-propelled Metered Dose Inhaler in Comparison to Combivent® CFC-propelled Metered Dose Inhaler. A Randomised, Double-blind, Active-controlled, Two-way Cross-over Study in COPD Patients

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Combivent® HFA inhalation aerosol
* Drug: Combivent® CFC inhalation aerosol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 40 years of age or older A diagnosis of COPD as defined by American Thoracic Society (ATS) criteria. Patients must have relatively stable, moderate to severe airway obstruction with a baseline FEV 1 <=65% of predicted normal and FEV1/FVC >=70%. A smoking history of more than ten pack-years. A pack-year is defined as the equivalent of smoking one pack of 20 cigarettes per day for a year Able to perform technical satisfactory pulmonary function test Able to be trained in the proper use of a MDI Having signed an informed consent from prior to participation in the trial Affiliation to the French social security system or beneficiary of such a system Exclusion Criteria: Significant disease other than COPD. 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 Clinical relevant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defines a disease listed as an exclusion criterion, the patient is excluded Serum glutamic oxaloacetic transaminase (SGOT) >80 IU/L; serum glutamic pyruvic transaminase (SGPT) >80IU/L, bilirubin >2.0mg/dL or creatinine >2.0mg/dL Serum potassium level above or below the normal range Total blood eosinophil count >=600/mm³ Recent history (i.e., one year or less) of myocardial infarction Recent history (i.e., three years or less) of heart failure or any cardiac arrhythmia requiring drug therapy History of cancer, other than treated basal cell carcinoma, within the last five years History of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis History of thoracotomy with pulmonary resection. History or a thoracotomy for other reasons should be evaluated as per exclusion criteria no. 1 History of asthma, allergic rhinitis or atopy History of or active alcohol or drug abuse Known active tuberculosis Upper respiratory tract infection or COPD exacerbation in the six weeks prior to screening visit or between the screening visit and visit 2 Known symptomatic prostatic hypertrophy or bladder neck obstruction Known narrow-angle glaucoma Current significant psychiatric disorders Regular use of daytime oxygen therapy Use of beta-blocker medications, mono-amine oxidase inhibitors or tricyclic antidepressants Use of cromolyn sodium or nedocromil sodium Use of antihistamines. Use of oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose before screening visit or a change between the screening visit and visit2) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20mg every other day Use of oral beta-adrenergics or long-acting beta-adrenergics such as salmeterol (Serevent®) and formoterol in the two weeks prior to the screening visit or between the screening visit and visit 2 Changes in the therapeutic plan within the last six weeks prior to the screening visit or between the screening visit and visit 2, excluding changes from long acting or oral beta-adrenergics to short acting inhaled beta-adrenergics for purposes of this trial Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception Known hypersensitivity to anti-cholinergic or beta-agonist drugs or any other component of either Combivent® formulations Use of an investigational drug within one month or six half lives prior to the screening visit Previous participation in this study Patient deprived of their freedom by a judicial or administrative decision Patient leaving in medical or social establishments Patient hospitalized for mental disorder without his (her) consent Patient under guardianship Patient in emergency situations

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: Combivent® HFA<br> | Drug: Combivent® HFA inhalation aerosol<br> <br> |
| Active Comparator: Combivent® CFC<br> | Drug: Combivent® CFC inhalation aerosol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with clinically significant changes in electrocardiogram (ECG) parameters (ventricular rate, PQ, QRS, QT and QTc intervals) |  | Baseline, up to 8 days after last treatment day | 
| Number of patients with clinically significant changes in vital signs (blood pressure, puls rate, respiratory rate) |  | Baseline, up to 8 days after last treatment day | 
| Changes in intra ocular pressure (IOP) |  | Baseline, up to 30 min after last drug administration | 
| Changes in serum potassium levels |  | Baseline, up to 180 min after last drug administration | 
| Changes in serum glucose levels |  | Baseline, up to 60 min after last drug administration | 
| Number of patients with clinically significant changes from baseline in clinical laboratory evaluations |  | Baseline, 8 days after last treatment day | 
| Number of patients with adverse events including paradoxical bronchospasm |  | Up to 8 days after last treatment day | 
| Number of patients with clinically significant changes from baseline in physical examination |  | Baseline, 8 days after last treatment day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 (forced expiratory volume in one second) |  | Baseline, up to 180 min after last drug administration | 
| Change in FVC (forced vital capacity) |  | Baseline, up to 180 min after last drug administration |