Combivent Respimat 1-year Safety Study in Patients With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate long-term safety and patient acceptability of COMBIVENT RESPIMAT Inhalation Spray as compared to the COMBIVENT Inhalation Aerosol Chlorofluorocarbon-Metered Dose Inhaler (CFC-MDI) and the free combination of ATROVENT Hydrofluoroalkane (HFA) and albuterol Hydrofluoroalkane (HFA) inhalation aerosols.

Official Title
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Patient Acceptability of Ipratropium Bromide/Albuteroll Delivered by the Respimat® Inhaler in Adults With Chronic Obstructive Pulmonary Disease

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Combivent CFC-MDI
* Drug: Combivent Respimat 20/100 mcg
* Drug: Atrovent HFA 42 mcg + Albuterol HFA 200 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: All patients must sign an informed consent consistent with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines prior to participation in the trial. Male or female patients 40 years of age or older. Patients must be current or ex-smokers with a smoking history of 10 pack-years. (Patients who have never smoked cigarettes must be excluded) Pack Years = Number of cigarettes/day x years of smoking 20 cigarettes/pack All patients must have a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (P95-4381), and must meet the following spirometric criteria at Visit 1:Relatively stable, moderate to severe airway obstruction with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) < 80% of predicted normal and FEV1/Forced Vital Capacity (FVC) < 70%. Spirometry should be done at baseline and approximately 1/2 hour following 4 inhalations of albuterol. Predicted normal values will be calculated according to European Coal and Steel Community (ECSC), European Community for Coal and Steel (ECCS), (R94-1408). For Height measured in inches Males: FEV1 predicted (L) = 4.30 x [height (inches) / 39.37]-0.029 x age (yrs) - 2.49 Females: FEV1 predicted (L) = 3.95 x [height (inches) / 39.37]-0.025 x age (yrs) - 2.60 For Height measured in meters Males: FEV1 predicted (L) = 4.30 x [height (meters)] - 0.029 x age (years) -2.49 Females: FEV1 predicted (L) = 3.95 x [height (meters)] - 0.025 x age (years) - 2.60 Patients must be able to perform all study related procedures and maintain study records during the study period as required in the protocol. Patients must be able to inhale medication in a competent manner from the RESPIMAT inhaler and from a metered dose inhaler (MDI). 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 which may influence the results of the study or the patient's ability to participate in the study. Patients with a recent history (i.e., one year or less) of myocardial infarction. Patients who have been hospitalized or being treated for heart failure within the past year. Patients with clinically unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy within the past year. Patients with a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with fully cured squamous cell or treated basal cell carcinoma are allowed). Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of a thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1. Patients with a current diagnosis of asthma. Patients with a history of significant alcohol or drug abuse. Patients with known active tuberculosis. Patients using beta blocker medications are excluded. Cardioselective beta blockers are allowed with caution. Beta blocker eye medications for treatment of non-narrow angle glaucoma are allowed. Patients who regularly use daytime oxygen therapy for more than 1 hour per day Continuous Positive Airway Pressure (CPAP for sleep apnea is allowed). Patients using oral corticosteroid medication at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day, except as required for treatment of exacerbation during the study. Pregnant or nursing women. Women of childbearing potential not using a medically approved means of contraception (i.e., oral or injectable contraceptives, intrauterine devices or diaphragm with spermicide, or transdermal hormonal patches). Abstinence will not be accepted as a medically approved means of contraception. Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years. Patients with known hypersensitivity to anticholinergic drugs, any other component of the ipratropium bromide/albuterol RESPIMAT solution including Benzalkonium chloride (BAC) and Ethylenediaminetetraacetic acid (EDTA) or the ipratropium bromide/albuterol Chlorofluorocarbons (CFC) MDI or Hydrofluoroalkane (HFA) components. Previous participation in this study. (The patient cannot re-enroll into this study.) Patients who are currently participating in another interventional study. Patients who have taken an investigational drug within 1 month or 6 half lives (whichever is greater) prior to screening. Patients currently in any pulmonary rehabilitation program or scheduled to participate in any such program during the study period.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combivent Respimat 20/100 microgram(mcg)<br>patient to take 1 inhalation 4 times a day | Drug: Combivent Respimat 20/100 mcg<br>* Open label randomized parallel<br>|
| Active Comparator: Combivent CFC-MDI 36/206 microgram-mcg<br>patient to take 2 inhalations 4 times a day | Drug: Combivent CFC-MDI<br>* 36/206 mcg Four times a day (QID)<br>|
| Active Comparator: Atrovent HFA 42 mcg + Albuterol HFA<br>patient to take 2 inhalations of each 4 times a day | Drug: Atrovent HFA 42 mcg + Albuterol HFA 200 mcg<br>* Open label randomized parallel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 48 | Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied). | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 3 | Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied). | 3 weeks | 
| Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 12 | Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied). | 12 weeks | 
| Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 24 | Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied). | 24 weeks | 
| Performance Domain Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 36 | Patient acceptability was assessed with the Performance Domain score from the PASAPQ. The score is a mean of 7 items on a scale from 0 (very dissatisfied) to 100 (very satisfied). | 36 weeks | 
| Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 0 | Patient satisfaction was assessed by asking: Overall, how satisfied are you with your inhaler?. Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied). | 0 weeks | 
| Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 3 | Patient satisfaction was assessed by asking: Overall, how satisfied are you with your inhaler?. Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied). | 3 weeks | 
| Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 12 | Patient satisfaction was assessed by asking: Overall, how satisfied are you with your inhaler?. Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied). | 12 weeks | 
| Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 24 | Patient satisfaction was assessed by asking: Overall, how satisfied are you with your inhaler?. Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied). | 24 weeks | 
| Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 36 | Patient satisfaction was assessed by asking: Overall, how satisfied are you with your inhaler?. Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied). | 36 weeks | 
| Overall Satisfaction Score From the Patient Satisfaction and Preference Questionnaire (PASAPQ) at Week 48 | Patient satisfaction was assessed by asking: Overall, how satisfied are you with your inhaler?. Responses were made on a scale from 1 (very dissatisfied) to 7 (very satisfied). | 48 weeks | 
| Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 0 | CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited). | 0 weeks | 
| Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 3 | CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited). | 3 weeks | 
| Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 12 | CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited). | 12 weeks | 
| Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 24 | CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited). | 24 weeks | 
| Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 36 | CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited). | 36 weeks | 
| Clinical COPD Questionnaire (CCQ) Symptom Domain Score at Week 48 | CCQ symptom domain score assessed patient feelings or limitations due to their COPD on a scale from 0 (not limited) to 6 (totally limited). | 48 weeks | 
| Physician's Global Evaluation at Week 0 | Physicians evaluated the patient's overall clinical condition on a scale ranging from poor (score 1 or 2) to excellent (score 7 or 8). | 0 weeks | 
| Physician's Global Evaluation at Week 3 | Physicians evaluated the patient's overall clinical condition on a scale ranging from poor (score 1 or 2) to excellent (score 7 or 8). | 3 weeks | 
| Physician's Global Evaluation at Week 12 | Physicians evaluated the patient's overall clinical condition on a scale ranging from poor (score 1 or 2) to excellent (score 7 or 8). | 12 weeks | 
| Physician's Global Evaluation at Week 24 | Physicians evaluated the patient's overall clinical condition on a scale ranging from poor (score 1 or 2) to excellent (score 7 or 8). | 24 weeks | 
| Physician's Global Evaluation at Week 36 | Physicians evaluated the patient's overall clinical condition on a scale ranging from poor (score 1 or 2) to excellent (score 7 or 8). | 36 weeks | 
| Physician's Global Evaluation at Week 48 | Physicians evaluated the patient's overall clinical condition on a scale ranging from poor (score 1 or 2) to excellent (score 7 or 8). | 48 weeks | 
| Change From Baseline in FEV1 at Day 1 | Change from test-day baseline in Forced Expiratory Volume in 1 second (FEV1) at 1 hour post dose on test day 1. | baseline, day 1 | 
| Change From Baseline in FEV1 at Week 12 | Change from test-day baseline in Forced Expiratory Volume in 1 second (FEV1) at 1 hour post dose at Week 12 | baseline, 12 weeks | 
| Change From Baseline in FEV1 at Week 24 | Change from test-day baseline in Forced Expiratory Volume in 1 second (FEV1) at 1 hour post dose at Week 24 | baseline, 24 weeks | 
| Change From Baseline in FEV1 at Week 48 | Change from test-day baseline in Forced Expiratory Volume in 1 second (FEV1) at 1 hour post dose at Week 48 | baseline, 48 weeks | 
| Change From Baseline in FVC at Day 1 | Change from test-day baseline in Forced Vital Capacity (FVC) at 1 hour post dose on test day 1. | baseline, day 1 | 
| Change From Baseline in FVC at Week 12 | Change from test-day baseline in Forced Vital Capacity (FVC) at 1 hour post dose at Week 12 | baseline, 12 weeks | 
| Change From Baseline in FVC at Week 24 | Change from test-day baseline in Forced Vital Capacity (FVC) at 1 hour post dose at Week 24 | baseline, 24 weeks | 
| Change From Baseline in FVC at Week 48 | Change from test-day baseline in Forced Vital Capacity (FVC) at 1 hour post dose at Week 48 | baseline, 48 weeks | 
| Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 0 | Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 0 | 0 weeks | 
| Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 3 | Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 3 | 3 weeks | 
| Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 12 | Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 12 | 12 weeks | 
| Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 24 | Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 24 | 24 weeks | 
| Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 36 | Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 36 | 36 weeks | 
| Mean Number of Puffs of Daily Rescue Medication Use in Two Weeks Prior to Week 48 | Mean number of puffs of daily rescue medication use (albuterol use per 24 hour period) in two weeks prior to week 48 | 48 weeks | 
| Number of Patients Having Chronic Obstructive Pulmonary Disease (COPD) Exacerbations |  | 48 weeks | 
| Number of Patients Having Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Leading to Hospitalization |  | 48 weeks |