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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
404
Respimat inhaler
2.5 µg tiotropium + 5 µg olodaterol
5 µg tiotropium + 5 µg olodaterol
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 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.
Time frame: 12 weeks
Adjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 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.
Time frame: 12 weeks
Adjusted Mean Inspiratory Capacity at Pre-exercise After 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.
Time frame: 12 weeks
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1
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1237.15.01503 Boehringer Ingelheim Investigational Site
Torrance, California, United States
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Springfield, Illinois, United States
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Lebanon, New Hampshire, United States
1237.15.01513 Boehringer Ingelheim Investigational Site
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1237.15.01514 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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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.
Time frame: 1 day
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment
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.
Time frame: 6 weeks
Adjusted Mean Inspiratory Capacity at Pre-exercise After 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.
Time frame: 1 day
Adjusted Mean Inspiratory Capacity at Pre-exercise After 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.
Time frame: 6 weeks
Adjusted Mean Slope of the Intensity of Breathing Discomfort on Day 1
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.
Time frame: 1 day
Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 6
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.
Time frame: 6 weeks
Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 12
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.
Time frame: 12 weeks
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) on Day 1
Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed on day 1
Time frame: 1 day
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 6 Weeks
Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 6 weeks of treatment
Time frame: 6 weeks
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 12 Weeks
Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 12 weeks of treatment
Time frame: 12 weeks