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

Phase 3

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: tiotropium + olodaterol (high dose); Device: Respimat inhaler; Drug: 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

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-02-01
• Study First Submitted QC: 2012-02-01
• Study First Posted: 2012-02-03
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Disposition First Submitted: 2014-04-03
• Disposition First Submitted QC: 2014-04-03
• Disposition First Posted: 2014-04-30
• Results First Submitted: 2015-06-19
• Results First Submitted QC: 2015-08-12
• Results First Posted: 2015-09-15
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-28
• Last Update Posted: 2016-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 404

Inclusion Criteria

Not provided

Exclusion Criteria

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

1237.15.01512 Boehringer Ingelheim Investigational Site; 🇺🇸 Hartford, Connecticut, 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

1237.15.01504 Boehringer Ingelheim Investigational Site; 🇺🇸 Livonia, Michigan, United States

1237.15.01511 Boehringer Ingelheim Investigational Site; 🇺🇸 St. Charles, Missouri, 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

1237.15.01514 Boehringer Ingelheim Investigational Site; 🇺🇸 Philadelphia, Pennsylvania, United States

1237.15.01516 Boehringer Ingelheim Investigational Site; 🇺🇸 Pittsburgh, Pennsylvania, United States

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