A Study to Determine the Effect of Tiotropium + Olodaterol Fixed Dose Combination on Exercise Endurance Time During Constant Work Rate Cycle Ergometry Test in COPD
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Drug: tiotropium + olodaterol (high dose)Device: Respimat inhalerDrug: tiotropium+olodaterol (low dose)Drug: placebo to tiotropium+olodaterol
- Registration Number
- NCT01525615
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study is to compare the effects of orally inhaled tiotropium + olodaterol fixed dose combination (2.5/5 µg; 5/5 µg) with placebo on exercise tolerance after 12 weeks of treatment in patients with COPD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 404
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description tiotropium+olodaterol high dose Respimat inhaler once daily 2 puffs, FDC solution for inhalation Respimat tiotropium+olodaterol low dose tiotropium+olodaterol (low dose) once daily 2 puffs, fixed dose combination (FDC) solution for inhalation Respimat placebo Respimat inhaler once daily 2 puffs, solution for inhalation Respimat tiotropium+olodaterol low dose Respimat inhaler once daily 2 puffs, fixed dose combination (FDC) solution for inhalation Respimat placebo placebo to tiotropium+olodaterol once daily 2 puffs, solution for inhalation Respimat tiotropium+olodaterol high dose tiotropium + olodaterol (high dose) once daily 2 puffs, FDC solution for inhalation Respimat
- Primary Outcome Measures
Name Time Method Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 12 Weeks 12 weeks Primary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.
- Secondary Outcome Measures
Name Time Method Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks 6 weeks Secondary endpoint was pre-exercise inspiratory capacity (IC) during constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) after 6 weeks of treatment.
Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 6 6 weeks Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment.
The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates favorable results.Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 6 Weeks 6 weeks Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 6 weeks of treatment
Adjusted Mean Inspiratory Capacity at Pre-exercise After 12 Weeks 12 weeks Secondary endpoint was pre-exercise inspiratory capacity (IC) before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) after 12 weeks of treatment.
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1 1 day Secondary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity on Day 1. Analysis of covariance model on log10 transformation data. Adjusted means are back transformed to report in original units. Standard errors (SEs) are calculated using the delta method.
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment 6 weeks Secondary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment.The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.
Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 12 12 weeks Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment.
The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates favorable results.Adjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 12 Weeks 12 weeks Key secondary endpoint was endurance time during endurance shuttle walk test to symptom limitation at 85% of predicted maximum oxygen consumption (VO2) peak after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.
Adjusted Mean Inspiratory Capacity at Pre-exercise After 1 Day 1 day Secondary endpoint was pre-exercise inspiratory capacity (IC) during constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) on Day 1.
Adjusted Mean Slope of the Intensity of Breathing Discomfort on Day 1 1 day Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 1 day of treatment.
The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates slowing down in decline in breathing, i.e., favorable results.Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) on Day 1 1 day Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed on day 1
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 12 Weeks 12 weeks Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 12 weeks of treatment
Trial Locations
- Locations (60)
1237.15.01503 Boehringer Ingelheim Investigational Site
🇺🇸Torrance, California, United States
1237.15.01506 Boehringer Ingelheim Investigational Site
🇺🇸Springfield, Illinois, United States
1237.15.01507 Boehringer Ingelheim Investigational Site
🇺🇸Iowa City, Iowa, United States
1237.15.01509 Boehringer Ingelheim Investigational Site
🇺🇸Lebanon, New Hampshire, United States
1237.15.01513 Boehringer Ingelheim Investigational Site
🇺🇸Charlotte, North Carolina, United States
1237.15.01504 Boehringer Ingelheim Investigational Site
🇺🇸Livonia, Michigan, United States
1237.15.01511 Boehringer Ingelheim Investigational Site
🇺🇸St. Charles, Missouri, United States
1237.15.01501 Boehringer Ingelheim Investigational Site
🇺🇸Greenville, South Carolina, United States
1237.15.01514 Boehringer Ingelheim Investigational Site
🇺🇸Philadelphia, Pennsylvania, United States
1237.15.01516 Boehringer Ingelheim Investigational Site
🇺🇸Pittsburgh, Pennsylvania, United States
1237.15.01508 Boehringer Ingelheim Investigational Site
🇺🇸Easley, South Carolina, United States
1237.15.01510 Boehringer Ingelheim Investigational Site
🇺🇸Richmond, Virginia, United States
1237.15.54501 Boehringer Ingelheim Investigational Site
🇦🇷Mendonza, Argentina
1237.15.11501 Boehringer Ingelheim Investigational Site
🇨🇦Hamilotn, Ontario, Canada
1237.15.11503 Boehringer Ingelheim Investigational Site
🇨🇦Hamilton, Ontario, Canada
1237.15.11504 Boehringer Ingelheim Investigational Site
🇨🇦Kingston, Ontario, Canada
1237.15.35852 Boehringer Ingelheim Investigational Site
🇫🇮Vaasa, Finland
1237.15.33504 Boehringer Ingelheim Investigational Site
🇫🇷Pessac, France
1237.15.33501 Boehringer Ingelheim Investigational Site
🇫🇷Strasbourg Cedex, France
1237.15.49507 Boehringer Ingelheim Investigational Site
🇩🇪Aschaffenburg, Germany
1237.15.49502 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1237.15.49501 Boehringer Ingelheim Investigational Site
🇩🇪Großhansdorf, Germany
1237.15.49509 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1237.15.49505 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany
1237.15.49508 Boehringer Ingelheim Investigational Site
🇩🇪Koblenz, Germany
1237.15.49506 Boehringer Ingelheim Investigational Site
🇩🇪Wiesloch, Germany
1237.15.36501 Boehringer Ingelheim Investigational Site
🇭🇺Deszk, Hungary
1237.15.36503 Boehringer Ingelheim Investigational Site
🇭🇺Nyiregyhaza, Hungary
1237.15.39512 Boehringer Ingelheim Investigational Site
🇮🇹Ferrara, Italy
1237.15.39504 Boehringer Ingelheim Investigational Site
🇮🇹Parma, Italy
1237.15.39503 Boehringer Ingelheim Investigational Site
🇮🇹Pavia, Italy
1237.15.39501 Boehringer Ingelheim Investigational Site
🇮🇹Pisa, Italy
1237.15.39509 Boehringer Ingelheim Investigational Site
🇮🇹Pisa, Italy
1237.15.39508 Boehringer Ingelheim Investigational Site
🇮🇹Sesto San Giovanni (MI), Italy
1237.15.34506 Boehringer Ingelheim Investigational Site
🇪🇸Alicante, Spain
1237.15.34501 Boehringer Ingelheim Investigational Site
🇪🇸Barakaldo (Bilbao), Spain
1237.15.34507 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1237.15.34009 Boehringer Ingelheim Investigational Site
🇪🇸Malaga, Spain
1237.15.34001 Boehringer Ingelheim Investigational Site
🇪🇸Santander, Spain
1237.15.44152 Boehringer Ingelheim Investigational Site
🇬🇧Leicester, United Kingdom
1237.15.44154 Boehringer Ingelheim Investigational Site
🇬🇧Liverpool, United Kingdom
1237.15.44153 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1237.15.44151 Boehringer Ingelheim Investigational Site
🇬🇧Manchester, United Kingdom
1237.15.44155 Boehringer Ingelheim Investigational Site
🇬🇧Norwich, United Kingdom
1237.15.44158 Boehringer Ingelheim Investigational Site
🇬🇧Plymouth, United Kingdom
1237.15.01512 Boehringer Ingelheim Investigational Site
🇺🇸Hartford, Connecticut, United States
1237.15.54502 Boehringer Ingelheim Investigational Site
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
1237.15.54503 Boehringer Ingelheim Investigational Site
🇦🇷Provincia de Buenos Aires, Argentina
1237.15.11505 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
1237.15.01505 Boehringer Ingelheim Investigational Site
🇺🇸Spartanburg, South Carolina, United States
1237.15.01502 Boehringer Ingelheim Investigational Site
🇺🇸Union, South Carolina, United States
1237.15.11502 Boehringer Ingelheim Investigational Site
🇨🇦Ste-Foy, Quebec, Canada
1237.15.35851 Boehringer Ingelheim Investigational Site
🇫🇮Helsinki, Finland
1237.15.35853 Boehringer Ingelheim Investigational Site
🇫🇮Turku, Finland
1237.15.36502 Boehringer Ingelheim Investigational Site
🇭🇺Pecs, Hungary
1237.15.36504 Boehringer Ingelheim Investigational Site
🇭🇺Budapest, Hungary
1237.15.39511 Boehringer Ingelheim Investigational Site
🇮🇹Roma, Italy
1237.15.39506 Boehringer Ingelheim Investigational Site
🇮🇹Trieste, Italy
1237.15.33502 Boehringer Ingelheim Investigational Site
🇫🇷Nîmes cedex 9, France
1237.15.49504 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany