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 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 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 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
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
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
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
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
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 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)
1012.56.01014 Boehringer Ingelheim Investigational Site
🇺🇸Houston, Texas, United States
1012.56.01043 Boehringer Ingelheim Investigational Site
🇺🇸Palo Alto, California, United States
1012.56.01036 Boehringer Ingelheim Investigational Site
🇺🇸Hartford, Connecticut, United States
1012.56.01071 Boehringer Ingelheim Investigational Site
🇺🇸Mobile, Alabama, United States
1012.56.01021 Boehringer Ingelheim Investigational Site
🇺🇸Riverside, California, United States
1012.56.01025 Boehringer Ingelheim Investigational Site
🇺🇸Stamford, Connecticut, United States
1012.56.01020 Boehringer Ingelheim Investigational Site
🇺🇸Sepulveda, California, United States
1012.56.01051 Boehringer Ingelheim Investigational Site
🇺🇸Jasper, Alabama, United States
1012.56.01069 Boehringer Ingelheim Investigational Site
🇺🇸Albuquerque, New Mexico, United States
1012.56.01029 Boehringer Ingelheim Investigational Site
🇺🇸Los Angeles, California, United States
1012.56.01093 Boehringer Ingelheim Investigational Site
🇺🇸Winter Park, Florida, United States
1012.56.01058 Boehringer Ingelheim Investigational Site
🇺🇸Brandon, Florida, United States
1012.56.01015 Boehringer Ingelheim Investigational Site
🇺🇸New Hyde Park, New York, United States
1012.56.01032 Boehringer Ingelheim Investigational Site
🇺🇸Killeen, Texas, United States
1012.56.01034 Boehringer Ingelheim Investigational Site
🇺🇸Sylvania, Ohio, United States
1012.56.01001 Boehringer Ingelheim Investigational Site
🇺🇸Melbourne, Florida, United States
1012.56.01012 Boehringer Ingelheim Investigational Site
🇺🇸Lakewood, California, United States
1012.56.01060 Boehringer Ingelheim Investigational Site
🇺🇸Philadelphia, Pennsylvania, United States
1012.56.01056 Boehringer Ingelheim Investigational Site
🇺🇸Wichita, Kansas, United States
1012.56.01018 Boehringer Ingelheim Investigational Site
🇺🇸Wheat Ridge, Colorado, United States
1012.56.01052 Boehringer Ingelheim Investigational Site
🇺🇸Pensecola, Florida, United States
1012.56.01083 Boehringer Ingelheim Investigational Site
🇺🇸Decatur, Georgia, United States
1012.56.01019 Boehringer Ingelheim Investigational Site
🇺🇸Olathe, Kansas, United States
1012.56.01022 Boehringer Ingelheim Investigational Site
🇺🇸Larchmont, New York, United States
1012.56.01070 Boehringer Ingelheim Investigational Site
🇺🇸Shreveport, Louisiana, United States
1012.56.01065 Boehringer Ingelheim Investigational Site
🇺🇸Clearwater, Florida, United States
1012.56.01067 Boehringer Ingelheim Investigational Site
🇺🇸Hershey, Pennsylvania, United States
1012.56.01035 Boehringer Ingelheim Investigational Site
🇺🇸Baltimore, Maryland, United States
1012.56.01003 Boehringer Ingelheim Investigational Site
🇺🇸Philadelphia, Pennsylvania, United States
1012.56.01068 Boehringer Ingelheim Investigational Site
🇺🇸New York City, New York, United States
1012.56.01087 Boehringer Ingelheim Investigational Site
🇺🇸East Providence, Rhode Island, United States
1012.56.01076 Boehringer Ingelheim Investigational Site
🇺🇸St. Louis, Missouri, United States
1012.56.01017 Boehringer Ingelheim Investigational Site
🇺🇸Raleigh, North Carolina, United States
1012.56.01057 Boehringer Ingelheim Investigational Site
🇺🇸Johnston, Rhode Island, United States
1012.56.54005 Instituto de Diagnóstico Cardiovascular La Plata
🇦🇷La Plata, Argentina
1012.56.82007 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1012.56.54012 Boehringer Ingelheim Investigational Site
🇦🇷Lanús, Argentina
1012.56.27006 Boehringer Ingelheim Investigational Site
🇿🇦Park Town West, South Africa
1012.56.82001 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1012.56.82006 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1012.56.64003 Boehringer Ingelheim Investigational Site
🇳🇿Hamilton, New Zealand
1012.56.3301A Hôpital Ambroise Paré
🇫🇷Marseille, France
1012.56.44006 Colchester General Hospital
🇬🇧Colchester, United Kingdom
1012.56.44007 Boehringer Ingelheim Investigational Site
🇬🇧Doncaster, United Kingdom
1012.56.82010 Boehringer Ingelheim Investigational Site
🇰🇷Geonggi-Do, Korea, Republic of
1012.56.64006 Boehringer Ingelheim Investigational Site
🇳🇿Tauranga, New Zealand
1012.56.30001 Boehringer Ingelheim Investigational Site
🇬🇷Athens, Greece
1012.56.30014 Boehringer Ingelheim Investigational Site
🇬🇷Nafplio, Greece
1012.56.3302B Cabinet Médical
🇫🇷Nice, France
1012.56.27005 Boehringer Ingelheim Investigational Site
🇿🇦Johannesburg, South Africa
1012.56.82005 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1012.56.44001 Medicine Evaluation Unit
🇬🇧Manchester, United Kingdom
1012.56.30013 Boehringer Ingelheim Investigational Site
🇬🇷Athens, Greece
1012.56.44002 Boehringer Ingelheim Investigational Site
🇬🇧Cambridge, United Kingdom
1012.56.82002 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1012.56.64001 Boehringer Ingelheim Investigational Site
🇳🇿Grafton / Auckland, New Zealand
1012.56.82009 Boehringer Ingelheim Investigational Site
🇰🇷Daegu, Korea, Republic of
1012.56.27002 Boehringer Ingelheim Investigational Site
🇿🇦Bellville, South Africa
1012.56.44009 Boehringer Ingelheim Investigational Site
🇬🇧Ballieston, Glasgow, United Kingdom
1012.56.44010 Boehringer Ingelheim Investigational Site
🇬🇧Windsor, United Kingdom
1012.56.27001 Boehringer Ingelheim Investigational Site
🇿🇦Cape Town, South Africa
1012.56.27008 Boehringer Ingelheim Investigational Site
🇿🇦Boksburg, South Africa
1012.56.27003 Boehringer Ingelheim Investigational Site
🇿🇦Paarl, South Africa
1012.56.44005 Morriston Hospital
🇬🇧Swansea, United Kingdom
1012.56.54014 Boehringer Ingelheim Investigational Site
🇦🇷Mendoza, Argentina
1012.56.07005 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
1012.56.48003 Boehringer Ingelheim Investigational Site
🇵🇱Wroclaw, Poland
1012.56.07002 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
1012.56.07003 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
1012.56.88603 National Taiwan University Hospital
🇨🇳Taipei, Taiwan
1012.56.88604 Chang Gong Memorial Hospital
🇨🇳Keelong Town, Taiwan
1012.56.88601 Chang Gung Memorial Hosp-Linkou
🇨🇳Taoyuan, Taiwan
1012.56.90002 Boehringer Ingelheim Investigational Site
🇹🇷Mersin, Turkey
1012.56.38005 Boehringer Ingelheim Investigational Site
🇺🇦Dnyepropyetrovsk, Ukraine
1012.56.38006 Boehringer Ingelheim Investigational Site
🇺🇦Donetsk, Ukraine
1012.56.38004 Boehringer Ingelheim Investigational Site
🇺🇦Kiev, Ukraine
1012.56.01050 Boehringer Ingelheim Investigational Site
🇺🇸Fort Collins, Colorado, United States
1012.56.01062 Boehringer Ingelheim Investigational Site
🇺🇸Wheat Ridge, Colorado, United States
1012.56.3302A Cabinet Médical
🇫🇷Nice, France
1012.56.01039 Boehringer Ingelheim Investigational Site
🇺🇸Phoenix, Arizona, United States
1012.56.01006 Boehringer Ingelheim Investigational Site
🇺🇸Birmingham, Alabama, United States
1012.56.01073 Boehringer Ingelheim Investigational Site
🇺🇸Nashville, Tennessee, United States
1012.56.01040 Boehringer Ingelheim Investigational Site
🇺🇸Denver, Colorado, United States
1012.56.01044 Boehringer Ingelheim Investigational Site
🇺🇸Minneapolis, Minnesota, United States
1012.56.01038 Boehringer Ingelheim Investigational Site
🇺🇸Oklahoma City, Oklahoma, United States
1012.56.01002 Boehringer Ingelheim Investigational Site
🇺🇸San Antonio, Texas, United States
1012.56.01053 Boehringer Ingelheim Investigational Site
🇺🇸San Antonio, Texas, United States
1012.56.01048 Boehringer Ingelheim Investigational Site
🇺🇸Tampa, Florida, United States
1012.56.01031 Boehringer Ingelheim Investigational Site
🇺🇸Toledo, Ohio, United States
1012.56.01089 Boehringer Ingelheim Investigational Site
🇺🇸Rancho Mirage, California, United States
1012.56.01033 Boehringer Ingelheim Investigational Site
🇺🇸San Jose, California, United States
1012.56.01045 Boehringer Ingelheim Investigational Site
🇺🇸Torrence, California, United States
1012.56.01088 Boehringer Ingelheim Investigational Site
🇺🇸Waterbury, Connecticut, United States
1012.56.01010 Boehringer Ingelheim Investigational Site
🇺🇸Clearwater, Florida, United States
1012.56.01007 Boehringer Ingelheim Investigational Site
🇺🇸Bay Pines, Florida, United States
1012.56.01024 Boehringer Ingelheim Investigational Site
🇺🇸Deland, Florida, United States
1012.56.01066 Boehringer Ingelheim Investigational Site
🇺🇸Bowling Green, Kentucky, United States
1012.56.01078 Boehringer Ingelheim Investigational Site
🇺🇸Asheville, North Carolina, United States
1012.56.01049 Boehringer Ingelheim Investigational Site
🇺🇸Reno, Nevada, United States
1012.56.01016 Boehringer Ingelheim Investigational Site
🇺🇸Medford, Oregon, United States
1012.56.01047 Boehringer Ingelheim Investigational Site
🇺🇸Fort Worth, Texas, United States
1012.56.01011 Boehringer Ingelheim Investigational Site
🇺🇸Spartanburg, South Carolina, United States
1012.56.01059 Boehringer Ingelheim Investigational Site
🇺🇸Roanoke, Virginia, United States
1012.56.01055 Boehringer Ingelheim Investigational Site
🇺🇸Salem, Virginia, United States
1012.56.01063 Boehringer Ingelheim Investigational Site
🇺🇸Bellington, Washington, United States
1012.56.01064 Boehringer Ingelheim Investigational Site
🇺🇸Spokane, Washington, United States
1012.56.01005 Boehringer Ingelheim Investigational Site
🇺🇸Spokane, Washington, United States
1012.56.01030 Boehringer Ingelheim Investigational Site
🇺🇸Tacoma, Washington, United States
1012.56.01074 Boehringer Ingelheim Investigational Site
🇺🇸Morgantown, West Virginia, United States
1012.56.54002 Boehringer Ingelheim Investigational Site
🇦🇷Capital Federal, Argentina
1012.56.54001 Centro Médico de la Dra. De Salvo
🇦🇷Capital Federal, Argentina
1012.56.54003 Policlínica Bancaria
🇦🇷Capital Federal, Argentina
1012.56.54010 Instituto Lanari
🇦🇷Capital Federal, Argentina
1012.56.54011 Boehringer Ingelheim Investigational Site
🇦🇷Capital Federal, Argentina
1012.56.54015 Boehringer Ingelheim Investigational Site
🇦🇷Capital Federal, Argentina
1012.56.54009 Instituto de Investigaciones Clínicas
🇦🇷Mar del Plata, Argentina
1012.56.3305A Centre hospitalier Germon & Gauthier
🇫🇷Béthune, France
1012.56.3303A Clinique de la Louvière
🇫🇷Lille Cedex, France
1012.56.3304A Centre Médical Erdre Saint Augustin
🇫🇷Nantes, France
1012.56.30009 Boehringer Ingelheim Investigational Site
🇬🇷Heraklion, Greece
1012.56.30007 Boehringer Ingelheim Investigational Site
🇬🇷Komotini, Greece
1012.56.82008 Boehringer Ingelheim Investigational Site
🇰🇷Gyeonggi-Do, Korea, Republic of
1012.56.64004 Boehringer Ingelheim Investigational Site
🇳🇿Dunedin, New Zealand
1012.56.64005 Boehringer Ingelheim Investigational Site
🇳🇿Wellington, New Zealand
1012.56.48002 Boehringer Ingelheim Investigational Site
🇵🇱Proszowice, Poland
1012.56.07009 Boehringer Ingelheim Investigational Site
🇷🇺St.Petersburg, Russian Federation
1012.56.27009 Boehringer Ingelheim Investigational Site
🇿🇦Orange Grove, South Africa
1012.56.90006 Boehringer Ingelheim Investigational Site
🇹🇷Istanbul, Turkey
1012.56.90005 Boehringer Ingelheim Investigational Site
🇹🇷Antalya, Turkey
1012.56.38001 Boehringer Ingelheim Investigational Site
🇺🇦Kiev, Ukraine
1012.56.44003 Boehringer Ingelheim Investigational Site
🇬🇧Bury St Edmonds, United Kingdom
1012.56.44008 The Staploe Medical Centre
🇬🇧Soham, United Kingdom
1012.56.27004 Boehringer Ingelheim Investigational Site
🇿🇦Cape Town, South Africa
1012.56.01077 Boehringer Ingelheim Investigational Site
🇺🇸Atlanta, Georgia, United States
1012.56.01004 Boehringer Ingelheim Investigational Site
🇺🇸Pittsburgh, Pennsylvania, United States
1012.56.01079 Boehringer Ingelheim Investigational Site
🇺🇸Ann Arbor, Michigan, United States
1012.56.01042 Boehringer Ingelheim Investigational Site
🇺🇸Winston-Salem, North Carolina, United States
1012.56.01037 Boehringer Ingelheim Investigational Site
🇺🇸Charleston, South Carolina, United States
1012.56.30002 Boehringer Ingelheim Investigational Site
🇬🇷Larissa, Greece
1012.56.30003 Boehringer Ingelheim Investigational Site
🇬🇷Thessaloniki, Greece
1012.56.48006 Boehringer Ingelheim Investigational Site
🇵🇱Krakow, Poland
1012.56.48004 Boehringer Ingelheim Investigational Site
🇵🇱Ostrow Wielkopolska, Poland
1012.56.48005 Boehringer Ingelheim Investigational Site
🇵🇱Poznan, Poland
1012.56.01082 Boehringer Ingelheim Investigational Site
🇺🇸Henderson, Nevada, United States
1012.56.01080 Boehringer Ingelheim Investigational Site
🇺🇸Brick, New Jersey, United States
1012.56.54006 CENTRO PRIVADO de MEDICINA RESPIRATORIA
🇦🇷Paraná, Argentina
1012.56.54008 HOSPITAL ITALIANO de ROSARIO
🇦🇷Rosario, Argentina
1012.56.30010 Boehringer Ingelheim Investigational Site
🇬🇷Korinthos, Greece
1012.56.48009 Boehringer Ingelheim Investigational Site
🇵🇱Bydgoszcz, Poland
1012.56.48010 Boehringer Ingelheim Investigational Site
🇵🇱Radom, Poland
1012.56.48001 Boehringer Ingelheim Investigational Site
🇵🇱Warsaw, Poland
1012.56.07010 Boehringer Ingelheim Investigational Site
🇷🇺Kazan, Russian Federation
1012.56.07007 Boehringer Ingelheim Investigational Site
🇷🇺St. Petersburg, Russian Federation
1012.56.88605 Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
1012.56.90003 Boehringer Ingelheim Investigational Site
🇹🇷Istanbul, Turkey
1012.56.38002 Boehringer Ingelheim Investigational Site
🇺🇦Kiev, Ukraine
1012.56.54004 Hospital Ramos Mejia
🇦🇷Capital Federal, Argentina
1012.56.54013 Boehringer Ingelheim Investigational Site
🇦🇷San Miguel de Tucumán, Argentina
1012.56.30011 Boehringer Ingelheim Investigational Site
🇬🇷Athens, Greece
1012.56.48007 Boehringer Ingelheim Investigational Site
🇵🇱Krakow, Poland
1012.56.48011 Boehringer Ingelheim Investigational Site
🇵🇱Warsaw, Poland
1012.56.07008 Boehringer Ingelheim Investigational Site
🇷🇺St. Petersburg, Russian Federation
1012.56.90001 Boehringer Ingelheim Investigational Site
🇹🇷Ankara, Turkey
1012.56.01075 Boehringer Ingelheim Investigational Site
🇺🇸Nashville, Tennessee, United States
1012.56.01090 Boehringer Ingelheim Investigational Site
🇺🇸Lafayette, Louisiana, United States
1012.56.01084 Boehringer Ingelheim Investigational Site
🇺🇸Greer, South Carolina, United States
1012.56.07001 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
1012.56.88602 Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
1012.56.54007 CLINICA PRIVADA de MONTE GRANDE
🇦🇷Monte Grande, Argentina
1012.56.01026 Boehringer Ingelheim Investigational Site
🇺🇸Charleston, South Carolina, United States
1012.56.01081 Boehringer Ingelheim Investigational Site
🇺🇸Greenville, South Carolina, United States
1012.56.01085 Boehringer Ingelheim Investigational Site
🇺🇸Greenville, South Carolina, United States
1012.56.01054 Boehringer Ingelheim Investigational Site
🇺🇸New Orleans, Louisiana, United States
1012.56.01072 Boehringer Ingelheim Investigational Site
🇺🇸New Orleans, Louisiana, United States
1012.56.01009 Boehringer Ingelheim Investigational Site
🇺🇸Richmond, Virginia, United States
1012.56.01013 Boehringer Ingelheim Investigational Site
🇺🇸Richmond, Virginia, United States
1012.56.01023 Boehringer Ingelheim Investigational Site
🇺🇸Panama City, Florida, United States
1012.56.01008 Boehringer Ingelheim Investigational Site
🇺🇸Coeur D'Alene, Idaho, United States
1012.56.01027 Boehringer Ingelheim Investigational Site
🇺🇸Cherry Hill, New Jersey, United States
1012.56.01028 Boehringer Ingelheim Investigational Site
🇺🇸Summit, New Jersey, United States