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Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease I

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00793624
Recruitment Status : Completed
First Posted : November 19, 2008
Results First Posted : June 5, 2014
Last Update Posted : June 27, 2014
Sponsor:
Information provided by:
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Olodaterol (BI 1744)
Drug: Formoterol
Drug: Placebo
Enrollment 906
Recruitment Details  
Pre-assignment Details Two subjects were randomized but not treated due to withdrawn consent and inability to perform spirometry prior to dosing.
Arm/Group Title Placebo Olodaterol (Olo) 5 mcg qd Olodaterol (Olo) 10 mcg qd Form 12 mcg
Hide Arm/Group Description Matching Placebo delivered by the Respimat Inhaler. Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler. Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler. Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Period Title: Overall Study
Started 225 227 225 227
Completed 168 191 186 184
Not Completed 57 36 39 43
Reason Not Completed
Adverse Event             18             16             15             20
Lost to Follow-up             2             2             4             0
Withdrawal by Subject             20             9             11             14
Lack of Efficacy             9             2             1             3
Non compliance with protocol             2             3             2             3
Other reason not described above             6             4             6             3
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Total
Hide Arm/Group Description Matching Placebo delivered by the Respimat Inhaler. Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler. Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler. Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler. Total of all reporting groups
Overall Number of Baseline Participants 225 227 225 227 904
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 225 participants 227 participants 225 participants 227 participants 904 participants
64.0  (8.4) 63.7  (9.1) 62.6  (8.8) 64.8  (8.6) 63.8  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 225 participants 227 participants 225 participants 227 participants 904 participants
Female
45
  20.0%
50
  22.0%
55
  24.4%
48
  21.1%
198
  21.9%
Male
180
  80.0%
177
  78.0%
170
  75.6%
179
  78.9%
706
  78.1%
Tiotropium (Tio) Use Stratum  
Measure Type: Number
Unit of measure:  Number of participants
Number Analyzed 225 participants 227 participants 225 participants 227 participants 904 participants
Non-tiotropium 169 168 167 169 673
Tiotropium 56 59 58 58 231
1.Primary Outcome
Title Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
Hide Description Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.009  (0.016) 0.142  (0.015) 0.156  (0.015) 0.168  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.151
Confidence Interval 95%
0.110 to 0.193
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.165
Confidence Interval 95%
0.124 to 0.206
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.177
Confidence Interval 95%
0.136 to 0.218
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg minus Placebo
2.Primary Outcome
Title Trough FEV1 Response at Week 24
Hide Description Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 205 220 219 215
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.056  (0.015) 0.021  (0.015) 0.028  (0.015) -0.002  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.078
Confidence Interval 95%
0.037 to 0.118
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.085
Confidence Interval 95%
0.044 to 0.125
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0088
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.054
Confidence Interval 95%
0.014 to 0.095
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg minus Placebo
3.Primary Outcome
Title Mahler Transitional Dyspnea Index Focal Score at 24 Weeks
Hide Description Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 192 212 207 202
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
2.046  (0.255) 2.234  (0.240) 2.068  (0.245) 1.818  (0.247)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5843
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.188
Confidence Interval 95%
-0.485 to 0.860
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.343
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9494
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.022
Confidence Interval 95%
-0.656 to 0.699
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.345
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5099
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.288
Confidence Interval 95%
-0.908 to 0.451
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.346
Estimation Comments Form 12 mcg minus Placebo
4.Primary Outcome
Title Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis
Hide Description This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis sets (FAS) of the trials NCT00793624 and NCT00796653. FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 413 433 427 417
Mean (Standard Error)
Unit of Measure: score on a scale
1.471  (0.155) 1.980  (0.175) 1.996  (0.170) 1.827  (0.168)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments Olo 5mcg minus placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0270
Comments [Not Specified]
Method pattern mixture model
Comments See Hogan, et. al. Hogan JW, Roy J, Korkontzelou C Tutorial in biostatistics:handling drop-out in longitudinal studies. Stat Med 23,1455–1497(2004)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.509
Confidence Interval 95%
0.058 to 0.960
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.230
Estimation Comments

Based on a pattern mixture model with four patterns based on time of dropout (i.e., day of last observed data)

1) day 43 or day 85, 2) day 127 or day 169, 3) day 225 or day 281, 4) day 337

Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments Olo 10 mcg minus placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0203
Comments See Hogan, et. al. Hogan JW, Roy J, Korkontzelou C Tutorial in biostatistics:handling drop-out in longitudinal studies. Stat Med 23,1455–1497(2004)
Method pattern mixture model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.525
Confidence Interval 95%
0.082 to 0.967
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.226
Estimation Comments

Based on a pattern mixture model with four patterns based on time of dropout (i.e., day of last observed data)

1) day 43 or day 85, 2) day 127 or day 169, 3) day 225 or day 281, 4) day 337

Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments Form 12mcg minus placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1166
Comments [Not Specified]
Method pattern mixture model
Comments See Hogan, et. al. Hogan JW, Roy J, Korkontzelou C Tutorial in biostatistics:handling drop-out in longitudinal studies. Stat Med 23,1455–1497(2004)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.355
Confidence Interval 95%
-0.088 to 0.799
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.226
Estimation Comments

Based on a pattern mixture model with four patterns based on time of dropout (i.e., day of last observed data)

1) day 43 or day 85, 2) day 127 or day 169, 3) day 225 or day 281, 4) day 337

5.Secondary Outcome
Title Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks
Hide Description Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 185 200 202 202
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
41.068  (1.038) 38.627  (0.995) 37.674  (0.998) 40.116  (0.994)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0816
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.442
Confidence Interval 95%
-5.190 to 0.307
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.401
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0155
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.394
Confidence Interval 95%
-6.141 to -0.648
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.400
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4954
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.952
Confidence Interval 95%
-3.691 to 1.787
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.396
Estimation Comments Form 12 mcg minus Placebo
6.Secondary Outcome
Title Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks
Hide Description Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 185 200 202 202
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
42.105  (1.027) 39.320  (0.986) 36.961  (0.989) 40.351  (0.992)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0450
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.785
Confidence Interval 95%
-5.507 to -0.063
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.387
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.144
Confidence Interval 95%
-7.864 to -2.425
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.386
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2061
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.754
Confidence Interval 95%
-4.474 to 0.966
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.386
Estimation Comments Form 12 mcg minus Placebo
7.Secondary Outcome
Title Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks
Hide Description Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 185 200 202 202
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
40.415  (1.057) 38.545  (1.000) 36.850  (1.015) 40.431  (1.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1878
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.871
Confidence Interval 95%
-4.655 to 0.914
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.419
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0126
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.565
Confidence Interval 95%
-6.364 to -0.767
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.427
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9913
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.016
Confidence Interval 95%
-2.782 to 2.814
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.426
Estimation Comments Form 12 mcg minus Placebo
8.Secondary Outcome
Title Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis
Hide Description Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). This is a combined analysis of the data from NCT00793624 and NCT00796653 showing adjusted values using a MMRM model.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis sets (FAS) of the trials NCT00793624 and NCT00796653. FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 387 416 414 408
Mean (Standard Error)
Unit of Measure: score on a scale
41.639  (0.718) 38.794  (0.693) 38.205  (0.695) 40.391  (0.699)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments Olo 5 mcg qd minus Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.846
Confidence Interval 95%
-4.751 to -0.940
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.972
Estimation Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments Olo 10 mcg qd minus Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.434
Confidence Interval 95%
-5.343 to -1.525
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.973
Estimation Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments Form 10 mcg qd minus Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2009
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.248
Confidence Interval 95%
-3.161 to 0.665
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.976
Estimation Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
9.Secondary Outcome
Title Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
Hide Description Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.015  (0.015) 0.201  (0.015) 0.181  (0.015) 0.221  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.186
Confidence Interval 95%
0.146 to 0.226
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.166
Confidence Interval 95%
0.126 to 0.206
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.206
Confidence Interval 95%
0.166 to 0.246
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Form 12 mcg minus Placebo
10.Secondary Outcome
Title Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
Hide Description Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.001  (0.015) 0.178  (0.015) 0.161  (0.015) 0.194  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.176
Confidence Interval 95%
0.136 to 0.217
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.160
Confidence Interval 95%
0.119 to 0.200
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.192
Confidence Interval 95%
0.152 to 0.233
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg minus Placebo
11.Secondary Outcome
Title Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
Hide Description Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.003  (0.015) 0.176  (0.015) 0.167  (0.015) 0.182  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.178
Confidence Interval 95%
0.137 to 0.219
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.170
Confidence Interval 95%
0.129 to 0.211
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.185
Confidence Interval 95%
0.144 to 0.226
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg minus Placebo
12.Secondary Outcome
Title Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
Hide Description Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.023  (0.016) 0.122  (0.015) 0.123  (0.015) 0.149  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.145
Confidence Interval 95%
0.103 to 0.186
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.146
Confidence Interval 95%
0.105 to 0.188
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.172
Confidence Interval 95%
0.130 to 0.214
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg minus Placebo
13.Secondary Outcome
Title Trough FEV1 Response at Week 2
Hide Description Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 205 220 219 215
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.019  (0.015) 0.068  (0.014) 0.060  (0.014) 0.061  (0.014)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.087
Confidence Interval 95%
0.048 to 0.126
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.079
Confidence Interval 95%
0.040 to 0.118
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.080
Confidence Interval 95%
0.040 to 0.119
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Form 12 mcg minus Placebo
14.Secondary Outcome
Title Trough FEV1 Response at Week 6
Hide Description Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 205 220 219 215
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.037  (0.015) 0.049  (0.014) 0.041  (0.014) 0.042  (0.014)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.086
Confidence Interval 95%
0.047 to 0.125
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.078
Confidence Interval 95%
0.038 to 0.117
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.079
Confidence Interval 95%
0.039 to 0.119
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Form 12 mcg minus Placebo
15.Secondary Outcome
Title Trough FEV1 Response at Week 12
Hide Description Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 205 220 219 215
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.027  (0.015) 0.056  (0.014) 0.048  (0.014) 0.033  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.083
Confidence Interval 95%
0.043 to 0.123
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.075
Confidence Interval 95%
0.035 to 0.114
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0037
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.059
Confidence Interval 95%
0.019 to 0.100
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Form 12 mcg minus Placebo
16.Secondary Outcome
Title Trough FEV1 Response at Week 18
Hide Description Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 205 220 219 215
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.019  (0.015) 0.046  (0.014) 0.026  (0.015) 0.023  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.065
Confidence Interval 95%
0.025 to 0.105
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0276
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.045
Confidence Interval 95%
0.005 to 0.085
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0426
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.042
Confidence Interval 95%
0.001 to 0.082
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg minus Placebo
17.Secondary Outcome
Title Trough FEV1 Response at Week 32
Hide Description Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 205 220 219 215
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.023  (0.015) 0.023  (0.015) 0.026  (0.015) 0.021  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0237
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.047
Confidence Interval 95%
0.006 to 0.087
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0175
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.049
Confidence Interval 95%
0.009 to 0.090
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0339
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.044
Confidence Interval 95%
0.003 to 0.085
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg minus Placebo
18.Secondary Outcome
Title Trough FEV1 Response at Week 40
Hide Description Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 205 220 219 215
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.020  (0.016) 0.020  (0.015) 0.017  (0.015) 0.004  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0537
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.040
Confidence Interval 95%
-0.001 to 0.081
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0808
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.037
Confidence Interval 95%
-0.004 to 0.078
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2579
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.024
Confidence Interval 95%
-0.017 to 0.065
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg minus Placebo
19.Secondary Outcome
Title Trough FEV1 Response at Week 48
Hide Description Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 205 220 219 215
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.065  (0.015) 0.003  (0.015) -0.009  (0.015) -0.006  (0.015)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.068
Confidence Interval 95%
0.027 to 0.109
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0069
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.059
Confidence Interval 95%
0.018 to 0.101
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.080
Confidence Interval 95%
0.040 to 0.119
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Form 12 mcg minus Placebo
20.Secondary Outcome
Title Peak FEV1 (0-3h) Response After 2 Weeks
Hide Description Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.100  (0.016) 0.277  (0.016) 0.250  (0.016) 0.290  (0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.177
Confidence Interval 95%
0.135 to 0.220
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.150
Confidence Interval 95%
0.108 to 0.193
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.190
Confidence Interval 95%
0.148 to 0.233
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Form 12 mcg minus Placebo
21.Secondary Outcome
Title Peak FEV1 (0-3h) Response After 6 Weeks
Hide Description Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.081  (0.016) 0.248  (0.016) 0.234  (0.016) 0.264  (0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.166
Confidence Interval 95%
0.124 to 0.209
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.152
Confidence Interval 95%
0.109 to 0.195
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.182
Confidence Interval 95%
0.139 to 0.226
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Form 12 mcg minus Placebo
22.Secondary Outcome
Title Peak FEV1 (0-3h) Response After 12 Weeks
Hide Description Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.082  (0.016) 0.247  (0.016) 0.241  (0.016) 0.256  (0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.165
Confidence Interval 95%
0.122 to 0.208
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.159
Confidence Interval 95%
0.116 to 0.203
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.174
Confidence Interval 95%
0.130 to 0.218
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Form 12 mcg minus Placebo
23.Secondary Outcome
Title Peak FEV1 (0-3h) Response After 24 Weeks
Hide Description Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.068  (0.017) 0.216  (0.016) 0.225  (0.016) 0.236  (0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.148
Confidence Interval 95%
0.104 to 0.191
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.167
Confidence Interval 95%
0.112 to 0.200
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.167
Confidence Interval 95%
0.123 to 0.211
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Form 12 mcg minus Placebo
24.Secondary Outcome
Title Peak FEV1 (0-3h) Response After 48 Weeks
Hide Description Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.053  (0.017) 0.192  (0.016) 0.193  (0.016) 0.215  (0.016)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.139
Confidence Interval 95%
0.095 to 0.183
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.140
Confidence Interval 95%
0.095 to 0.184
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.162
Confidence Interval 95%
0.117 to 0.206
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Form 12 mcg minus Placebo
25.Secondary Outcome
Title Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
Hide Description Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.076  (0.028) 0.299  (0.027) 0.311  (0.027) 0.383  (0.027)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.223
Confidence Interval 95%
0.149 to 0.297
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.235
Confidence Interval 95%
0.161 to 0.309
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.307
Confidence Interval 95%
0.233 to 0.381
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Form 12 mcg minus Placebo
26.Secondary Outcome
Title Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
Hide Description Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.016  (0.028) 0.252  (0.027) 0.265  (0.027) 0.326  (0.027)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.236
Confidence Interval 95%
0.161 to 0.310
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.249
Confidence Interval 95%
0.175 to 0.324
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.310
Confidence Interval 95%
0.235 to 0.384
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Form 12 mcg minus Placebo
27.Secondary Outcome
Title Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
Hide Description Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.023  (0.028) 0.233  (0.027) 0.278  (0.027) 0.300  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.210
Confidence Interval 95%
0.135 to 0.285
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.254
Confidence Interval 95%
0.179 to 0.329
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.038
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.276
Confidence Interval 95%
0.201 to 0.352
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.039
Estimation Comments Form 12 mcg minus Placebo
28.Secondary Outcome
Title Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
Hide Description Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.037  (0.029) 0.220  (0.027) 0.252  (0.028) 0.279  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.182
Confidence Interval 95%
0.107 to 0.258
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.039
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.215
Confidence Interval 95%
0.139 to 0.291
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.039
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.242
Confidence Interval 95%
0.166 to 0.318
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.039
Estimation Comments Form 12 mcg minus Placebo
29.Secondary Outcome
Title Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
Hide Description Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 217 222 223 223
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.016  (0.029) 0.196  (0.028) 0.219  (0.028) 0.260  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.179
Confidence Interval 95%
0.103 to 0.256
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.039
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis