Respimat® Combivent Trial in Chronic Obstructive Pulmonary Disease (COPD)
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Drug: Placebo via corresponding inhaler for blinding purposes
- Registration Number
- NCT00400153
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study is to compare the effect of ipratropium bromide/salbutamol inhalation spray combination administered by the Respimat® inhaler (20 mcg/100 mcg), ipratropium bromide inhalation spray administered by the Respimat® inhaler (20 mcg), and COMBIVENT® MDI administered q.i.d on FEV1 at intervals over a treatment period of 12 weeks in patients with COPD. Specifically, non-inferiority of Combivent Respimat® to COMBIVENT® MDI in FEV1 AUC from 0 to 6 hours , superiority of Combivent Respimat® to Atrovent Respimat® monotherapy in FEV1 AUC from 0 to 4 hours, and non-inferiority of Combivent Respimat® to Atrovent Respimat® monotherapy in FEV1 AUC from 4 to 6 hours will be analyzed. In addition, steady state pharmacokinetics over one dosing interval following 4 weeks of therapy will be characterized in a subgroup of patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1480
Outpatients of either sex, 40 years or older, with a diagnosis of COPD (FEV1 65% predicted normal and FEV1/FVC 70%).
Patients with significant diseases other than COPD that 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, with a history of asthma or allergic rhinitis, who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy or using oral corticosteroid me dication at unstable doses (i.e., less than 6 weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day will be excluded.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description COMBIVENT Respimat 20/100 mcg Placebo via corresponding inhaler for blinding purposes - COMBIVENT CFC-MDI 36/206 mcg Placebo via corresponding inhaler for blinding purposes - Ipratropium Respimat 20 mcg Atrovent Respimat (20 mcg) - Ipratropium Respimat 20 mcg Placebo via corresponding inhaler for blinding purposes - COMBIVENT CFC-MDI 36/206 mcg COMBIVENT MDI (36/206 mcg) - COMBIVENT Respimat 20/100 mcg Combivent Respimat (20 mcg/100 mcg) -
- Primary Outcome Measures
Name Time Method FEV1 AUC0-4 at Day 85 Before drug administration to 4 hours after drug administration on Day 85 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 85
FEV1 AUC4-6 at Day 85 Between 4 hours and 6 hours after drug administration on Day 85 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 85
FEV1 AUC0-6 at Day 85 Before drug administration to 6 hours after drug administration on Day 85 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 85
- Secondary Outcome Measures
Name Time Method FEV1 AUC0-6 at Day 1 Before drug administration to 6 hours after drug administration on Day 1 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 1
FEV1 AUC0-6 at Day 29 Before drug administration to 6 hours after drug administration on Day 29 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 29
FEV1 AUC0-6 at Day 57 Before drug administration to 6 hours after drug administration on Day 57 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 57
FEV1 AUC0-4 at Day 1 Before drug administration to 4 hours after drug administration on Day 1 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 1
FEV1 AUC4-6 at Day 1 Between 4 hours and 6 hours after drug administration on Day 1 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 1
FEV1 AUC0-4 at Day 29 Before drug administration to 4 hours after drug administration on Day 29 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 29
FEV1 AUC0-4 at Day 57 Before drug administration to 4 hours after drug administration on Day 57 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 57
FEV1 AUC4-6 at Day 29 Between 4 hours and 6 hours after drug administration on Day 29 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 29
Peak FEV1 Response at Day 1 Within the first 2-hour post-treatment interval on Day 1 Maximum change in recorded FEV1 value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 1
Time to Onset of Therapeutic FEV1 Response at Day 1 Within the first 2-hour post-treatment interval at Day 1 Achievement of recorded FEV1 measurement of at least 1.15 times of the corresponding test-day baseline value at any time during the first 2 hours of observation after drug administration at Day 1
FEV1 AUC4-6 at Day 57 Between 4 hours and 6 hours after drug administration on Day 57 Area between the test-day baseline FEV1 and the FEV1 change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 57
Peak FEV1 Response at Day 57 Within the first 2-hour post-treatment interval on Day 57 Maximum change in recorded FEV1 value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 57
Time to Onset of Therapeutic FEV1 Response at Day 57 Within the first 2-hour post-treatment interval at Day 57 Achievement of recorded FEV1 measurement of at least 1.15 times of the corresponding test-day baseline value at any time during the first 2 hours of observation after drug administration at Day 57
Time to Onset of Therapeutic FEV1 Response at Day 85 Within the first 2-hour post-treatment interval at Day 85 Achievement of recorded FEV1 measurement of at least 1.15 times of the corresponding test-day baseline value at any time during the first 2 hours of observation after drug administration at Day 85
Duration of Therapeutic FEV1 Response at Day 1 During the 6-hour observation period after drug administration at Day 1 The time interval between the onset and the the termination of a therapeutic FEV1 response (at least 1.15 times the corresponding test-day baseline value) during the 6-hour observation period at Day 1
Duration of Therapeutic FEV1 Response at Day 29 During the 6-hour observation period after drug administration at Day 29 The time interval between the onset and the the termination of a therapeutic FEV1 response (at least 1.15 times the corresponding test-day baseline value) during the 6-hour observation period at Day 29
Duration of Therapeutic FEV1 Response at Day 57 During the 6-hour observation period after drug administration at Day 57 The time interval between the onset and the the termination of a therapeutic FEV1 response (at least 1.15 times the corresponding test-day baseline value) during the 6-hour observation period at Day 57
Duration of Therapeutic FEV1 Response at Day 85 During the 6-hour observation period after drug administration at Day 85 The time interval between the onset and the the termination of a therapeutic FEV1 response (at least 1.15 times the corresponding test-day baseline value) during the 6-hour observation period at Day 85
Time to Peak FEV1 Response at Day 1 Within the 6-hour post-treatment observation period at Day 1 The first time point at which the maximum change in recorded FEV1 data from the corresponding test-day baseline occurred during the 6-hours observation period after drug administration at Day 1
Time to Peak FEV1 Response at Day 29 Within the 6-hour post-treatment observation period at Day 29 The first time point at which the maximum change in recorded FEV1 data from the corresponding test-day baseline occurred during the 6-hours observation period after drug administration at Day 29
Peak FEV1 Response at Day 29 Within the first 2-hour post-treatment interval on Day 29 Maximum change in recorded FEV1 value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 29
Peak FEV1 Response at Day 85 Within the first 2-hour post-treatment interval on Day 85 Maximum change in recorded FEV1 value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 85
Time to Onset of Therapeutic FEV1 Response at Day 29 Within the first 2-hour post-treatment interval at Day 29 Achievement of recorded FEV1 measurement of at least 1.15 times of the corresponding test-day baseline value at any time during the first 2 hours of observation after drug administration at Day 29
Time to Peak FEV1 Response at Day 57 Within the 6-hour post-treatment observation period at Day 57 The first time point at which the maximum change in recorded FEV1 data from the corresponding test-day baseline occurred during the 6-hours observation period after drug administration at Day 57
Time to Peak FEV1 Response at Day 85 Within the 6-hour post-treatment observation period at Day 85 The first time point at which the maximum change in recorded FEV1 data from the corresponding test-day baseline occurred during the 6-hours observation period after drug administration at Day 85
FVC AUC0-6 at Day 1 Before drug administration to 6 hours after drug administration at Day 1 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 1
FVC AUC0-6 at Day 29 Before drug administration to 6 hours after drug administration at Day 29 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 29
FVC AUC0-6 at Day 57 Before drug administration to 6 hours after drug administration on Day 57 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 57
FVC AUC0-6 at Day 85 Before drug administration to 6 hours after drug administration on Day 85 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 6 hours divided by 6 at Day 85
FVC AUC0-4 at Day 1 Before drug administration to 4 hours after drug administration on Day 1 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 1
FVC AUC0-4 at Day 29 Before drug administration to 4 hours after drug administration on Day 29 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 29
FVC AUC0-4 at Day 57 Before drug administration to 4 hours after drug administration on Day 57 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 57
FVC AUC0-4 at Day 85 Before drug administration to 4 hours after drug administration on Day 85 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 0 to 4 hours divided by 4 at Day 85
FVC AUC4-6 at Day 1 Between 4 hours and 6 hours after drug administration on Day 1 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 1
FVC AUC4-6 at Day 29 Between 4 hours and 6 hours after drug administration on Day 29 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 29
FVC AUC4-6 at Day 57 Between 4 hours and 6 hours after drug administration on Day 57 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 57
FVC AUC4-6 at Day 85 Between 4 hours and 6 hours after drug administration on Day 85 Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 85
Peak FVC Response at Day 1 Within the first 2-hour post-treatment interval at Day 1 Maximum change in recorded FVC value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 1
Peak FVC Response at Day 29 Within the first 2-hour post-treatment interval at Day 29 Maximum change in recorded FVC value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 29
Peak FVC Response at Day 57 Within the first 2-hour post-treatment interval at Day 57 Maximum change in recorded FVC value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 57
Peak FVC Response at Day 85 Within the first 2-hour post-treatment interval at Day 85 Maximum change in recorded FVC value from the corresponding test-day baseline within the first 2 hours after drug administration on Day 85
Rescue Medication Use on Pulmonary Test Day 1 During the 6-hour pulmonary function testing after drug administration on Day 1 Number of patients used rescue medication during the 6-hour pulmonary function testing after drug administration on Day 1
Rescue Medication Use on Pulmonary Test Day 29 During the 6-hour pulmonary function testing after drug administration on Day 29 Number of patients used rescue medication during the 6-hour pulmonary function testing after drug administration on Day 29
Rescue Medication Use on Pulmonary Test Day 57 During the 6-hour pulmonary function testing after drug administration on Day 57 Number of patients used rescue medication during the 6-hour pulmonary function testing after drug administration on Day 57
Rescue Medication Use on Pulmonary Test Day 85 During the 6-hour pulmonary function testing after drug administration on Day 85 Number of patients used rescue medication during the 6-hour pulmonary function testing after drug administration on Day 85
Night-time Rescue Medication Use During the 2-week baseline washout period and the 12-week treatment period The mean number of puffs of rescue medication used during the night-time per week during the entire study (including baseline and on-treatment period)
Daytime Rescue Medication Use During the 2-week baseline washout period and the 12-week treatment period The mean number of puffs of rescue medication used during the daytime per week during the entire study (including baseline and on-treatment period)
Night-time Symptom Score During the 2-week baseline washout period and the 12-week treatment period The weekly mean night-time symptom score per week during the entire study (including baseline and on-treatment period).
Night-time COPD symptoms: 0=none 1=some - slept well 2=woke once 3=woke several times 4=woke most of nightDaytime Symptom Score During the 2-week baseline washout period and the 12-week treatment period The weekly mean daytime symptom score per week during the entire study (including baseline and on-treatment period).
Daytime COPD symptoms: 0=none 1=occasional 2=frequent, no interference with activities 3=most of day, interference with activities 4=prevent working and activitiesTrough Peak Expiratory Flow Rate (PEFR) During the 2-week baseline washout period and the 12-week treatment period and PEFR taken before administration of study medication The weekly mean trough PEFR during the entire study (including baseline and on-treatment period)
Physician's Global Evaluation Score on Pulmonary Function Testing Day 29 Prior to pulmonary function test on Day 29 Physician's Global Evaluation score is based on the need for concomitant medication, number and severity of exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, etc.
Score: 1,2 = poor; 3,4 = fair; 5,6 =good; 7,8 = excellent.Physician's Global Evaluation Score on Pulmonary Function Testing Day 57 Prior to pulmonary function test on Day 57 Physician's Global Evaluation score is based on the need for concomitant medication, number and severity of exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, etc.
Score: 1,2 = poor; 3,4 = fair; 5,6 =good; 7,8 = excellent.Physician's Global Evaluation Score on Pulmonary Function Testing Day 85 Prior to pulmonary function test on Day 85 Physician's Global Evaluation score is based on the need for concomitant medication, number and severity of exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, etc.
Score: 1,2 = poor; 3,4 = fair; 5,6 =good; 7,8 = excellent.Percentage of Patients With Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the On-treatment Period During the 12-week on-treatment period COPD exacerbation is defined as an increase or new onset of more than one of the following respiratory symptoms (cough, sputum, sputum purulence, wheezing, dyspnea, and chest tightness) having a duration of three or more days requiring treatment with an antibiotic and/or systemic steroids with or without hospital admission.
COPD Exacerbation Rate During the On-treatment Period During the 12-week on-treatment period Proportion of patients experiencing a COPD exacerbation per patient year. COPD exacerbation is defined as an increase or new onset of more than one of the following respiratory symptoms (cough, sputum, sputum purulence, wheezing, dyspnea, and chest tightness) having a duration of three or more days requiring treatment with an antibiotic and/or systemic steroids with or without hospital admission.
COPD Exacerbation During the On-treatment Period During the 12-week on-treatment period COPD exacerbation is defined as an increase or new onset of more than one of the following respiratory symptoms (cough, sputum, sputum purulence, wheezing, dyspnea, and chest tightness) having a duration of three or more days requiring treatment with an antibiotic and/or systemic steroids with or without hospital admission.
Frequency Distribution of Satisfaction Rating With Inhaler Attributes 12 weeks Mean Rating Scores of Satisfaction With Inhaler - Overall Feeling of Inhaling Medicine 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - Feeling That the Inhaled Dose Goes to the Lung 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - Telling the Amount of Medication Left 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - The Inhaler Works Reliably 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - Ease of Inhaling a Dose From the Inhaler 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - Instructions for Use 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - The Inhaler is Durable 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - Using the Inhaler 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - Speed of Medicine Coming Out of the Inhaler 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Mean Rating Scores of Satisfaction With Inhaler - Overall Satisfaction With Inhaler 12 weeks Patients rated their response on a seven point Likert scale:
1 = very dissatisfied, 2 = dissatisfied, 3 = somewhat dissatisfied, 4 = neither satisfied nor dissatisfied, 5 = somewhat satisfied, 6 = satisfied, 7 = very satisfied.Device Preference (Respimat or MDI) 12 weeks Frequency of patients due to device preference
Rating of Action of Turning Clear Base of Respimat 12 weeks Frequency of patients due to rating of action of turning clear base of Respimat
Noncompartmental Pharmacokinetic Parameters of Ipratropium at Steady State Before drug administration to 6 hours after drug administration on Day 29 Geometric mean area under the plasma drug concentration time curve over one dosing interval (AUCτ). Each patient had eight plasma samples (trough pre-dose, 5, 15, 30, and 60 minutes post-dose, as well as 2, 4, and 6 hours post-dose).
Noncompartmental Parameters of Albuterol at Steady State Before drug administration to 6 hours after drug administration on Day 29 Geometric mean area under the plasma drug concentration time curve over one dosing interval (AUCτ). Each patient had eight plasma samples (trough pre-dose, 5, 15, 30, and 60 minutes post-dose, as well as 2, 4, and 6 hours post-dose).
Cumulative Amounts of Ipratropium [μg] Excreted in Urine for 0-2 Hours Before drug administration to 2 hours after drug administration on Day 29 Cumulative amounts of Ipratropium \[μg\] excreted in urine - Planned time intervals 0-2, ss
Cumulative Amounts of Albuterol [μg] Excreted in Urine for 0-2 Hours Before drug administration to 2 hours after drug administration on Day 29 Cumulative amounts of Albuterol \[μg\] excreted in urine - Planned time intervals 0-2,ss.
Cumulative Amounts of Ipratropium [μg] Excreted in Urine for 0-6 Hours Before drug administration to 6 hours after drug administration on Day 26 Cumulative amounts of Ipratropium \[μg\] excreted in urine - Planned time intervals 0-6,ss
Cumulative Amounts of Albuterol [μg] Excreted in Urine for 0-6 Hours Before drug administration to 6 hours after drug administration on Day 29 Cumulative amounts of Albuterol \[μg\] excreted in urine - Planned time intervals 0-6, ss
Trial Locations
- Locations (180)
1012.56.01006 Boehringer Ingelheim Investigational Site
🇺🇸Birmingham, Alabama, United States
1012.56.01051 Boehringer Ingelheim Investigational Site
🇺🇸Jasper, Alabama, United States
1012.56.01071 Boehringer Ingelheim Investigational Site
🇺🇸Mobile, Alabama, United States
1012.56.01039 Boehringer Ingelheim Investigational Site
🇺🇸Phoenix, Arizona, United States
1012.56.01012 Boehringer Ingelheim Investigational Site
🇺🇸Lakewood, California, United States
1012.56.01029 Boehringer Ingelheim Investigational Site
🇺🇸Los Angeles, California, United States
1012.56.01043 Boehringer Ingelheim Investigational Site
🇺🇸Palo Alto, California, United States
1012.56.01089 Boehringer Ingelheim Investigational Site
🇺🇸Rancho Mirage, California, United States
1012.56.01021 Boehringer Ingelheim Investigational Site
🇺🇸Riverside, California, United States
1012.56.01033 Boehringer Ingelheim Investigational Site
🇺🇸San Jose, California, United States
Scroll for more (170 remaining)1012.56.01006 Boehringer Ingelheim Investigational Site🇺🇸Birmingham, Alabama, United States