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

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: NCT00796653
Recruitment Status : Completed
First Posted : November 24, 2008
Results First Posted : June 16, 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 937
Recruitment Details  
Pre-assignment Details Three patients were randomized but not treated due to withdrawn consent and findings on pre-dose ECG prior to receiving study medication.
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 235 232 234 233
Completed 184 195 198 193
Not Completed 51 37 36 40
Reason Not Completed
Adverse Event             19             16             16             16
Lost to Follow-up             2             1             2             3
Withdrawal by Subject             16             8             8             13
Lack of Efficacy             8             1             3             2
Non compliance with protocol             2             2             0             2
Other reason not described above             4             9             7             4
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 235 232 234 233 934
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 235 participants 232 participants 234 participants 233 participants 934 participants
63.9  (7.8) 63.7  (8.8) 63.8  (8.5) 65.0  (8.2) 64.183  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 235 participants 232 participants 234 participants 233 participants 934 participants
Female
40
  17.0%
45
  19.4%
50
  21.4%
41
  17.6%
176
  18.8%
Male
195
  83.0%
187
  80.6%
184
  78.6%
192
  82.4%
758
  81.2%
Tiotropium (Tio) Use Stratum  
Measure Type: Number
Unit of measure:  Number of participants
Number Analyzed 235 participants 232 participants 234 participants 233 participants 934 participants
Non-tiotropium 173 174 172 174 693
Tiotropium 62 58 62 59 241
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.013  (0.014) 0.116  (0.014) 0.140  (0.014) 0.137  (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 0.129
Confidence Interval 95%
0.091 to 0.167
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.154
Confidence Interval 95%
0.116 to 0.191
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.150
Confidence Interval 95%
0.112 to 0.188
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 232 229 228 229
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.055  (0.014) -0.003  (0.014) 0.014  (0.014) -0.013  (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 0.0055
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 0.053
Confidence Interval 95%
0.015 to 0.090
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.0003
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 0.069
Confidence Interval 95%
0.032 to 0.106
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.0270
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%
0.005 to 0.080
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 221 221 220 215
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
1.102  (0.229) 1.504  (0.225) 1.521  (0.225) 1.703  (0.228)
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 0.1999
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 0.402
Confidence Interval 95%
-0.213 to 1.018
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.314
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 0.1818
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 0.419
Confidence Interval 95%
-0.196 to 1.035
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.314
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 0.0572
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 0.602
Confidence Interval 95%
-0.019 to 1.222
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.316
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 (2-Sided) 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 [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 (Net)
Estimated Value 0.525
Confidence Interval (2-Sided) 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 (Net)
Estimated Value 0.355
Confidence Interval (2-Sided) 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 202 216 212 206
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
42.120  (0.995) 38.970  (0.965) 38.597  (0.969) 40.704  (0.984)
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 0.0197
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 -3.150
Confidence Interval 95%
-5.796 to -0.503
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.349
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 0.0094
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 -3.524
Confidence Interval 95%
-6.180 to -0.867
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.354
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 0.2995
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 -1.416
Confidence Interval 95%
-4.093 to 1.261
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.365
Estimation Comments Form 12 mcg minus Placebo
6.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 202 216 212 206
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
39.914  (1.022) 39.562  (0.986) 38.824  (0.991) 40.025  (0.996)
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 0.7995
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 -0.352
Confidence Interval 95%
-3.068 to 2.365
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.385
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 0.4336
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 -1.090
Confidence Interval 95%
-3.818 to 1.639
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.391
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 0.9365
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 0.111
Confidence Interval 95%
-2.625 to 2.848
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.395
Estimation Comments Form 12 mcg minus Placebo
7.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 202 216 212 206
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
42.679  (0.983) 40.054  (0.955) 40.190  (0.963) 39.521  (0.975)
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 0.0491
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 -2.625
Confidence Interval 95%
-5.241 to -0.010
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.333
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 0.0636
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 -2.489
Confidence Interval 95%
-5.119 to 0.141
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.341
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 0.0194
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 -3.158
Confidence Interval 95%
-5.806 to -0.511
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.350
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
Least Squares 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 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 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 -2.846
Confidence Interval (2-Sided) 95%
-4.751 to -0.940
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.972
Estimation Comments [Not Specified]
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 0.0004
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 -3.434
Confidence Interval (2-Sided) 95%
-5.343 to -1.525
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.973
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg
Comments Form 12 mcg 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 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 -1.248
Confidence Interval (2-Sided) 95%
-3.161 to 0.665
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.976
Estimation Comments [Not Specified]
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.021  (0.013) 0.181  (0.014) 0.214  (0.013) 0.183  (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 0.160
Confidence Interval 95%
0.123 to 0.196
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.193
Confidence Interval 95%
0.157 to 0.229
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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%
0.126 to 0.199
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.010  (0.014) 0.162  (0.014) 0.181  (0.014) 0.174  (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 0.172
Confidence Interval 95%
0.136 to 0.209
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.192
Confidence Interval 95%
0.155 to 0.228
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.184
Confidence Interval 95%
0.148 to 0.221
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.008  (0.014) 0.138  (0.014) 0.167  (0.014) 0.163  (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 0.145
Confidence Interval 95%
0.108 to 0.182
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.175
Confidence Interval 95%
0.138 to 0.212
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.170
Confidence Interval 95%
0.133 to 0.208
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.025  (0.014) 0.093  (0.014) 0.116  (0.014) 0.104  (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 0.118
Confidence Interval 95%
0.080 to 0.156
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 0.141
Confidence Interval 95%
0.103 to 0.180
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 0.129
Confidence Interval 95%
0.091 to 0.168
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
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 232 229 228 229
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.016  (0.013) 0.053  (0.013) 0.103  (0.013) 0.033  (0.013)
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 0.069
Confidence Interval 95%
0.033 to 0.105
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
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 0.119
Confidence Interval 95%
0.083 to 0.155
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
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 0.0071
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%
0.013 to 0.085
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
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 232 229 228 229
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.036  (0.013) 0.047  (0.013) 0.068  (0.013) 0.034  (0.013)
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 0.084
Confidence Interval 95%
0.048 to 0.120
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
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 0.104
Confidence Interval 95%
0.068 to 0.141
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
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 0.070
Confidence Interval 95%
0.034 to 0.106
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
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 232 229 228 229
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.041  (0.014) 0.018  (0.013) 0.052  (0.013) 0.024  (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 0.0017
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%
0.022 to 0.095
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.093
Confidence Interval 95%
0.057 to 0.130
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.0005
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%
0.028 to 0.101
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 232 229 228 229
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.036  (0.014) 0.013  (0.014) 0.049  (0.013) 0.015  (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 0.0085
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 0.050
Confidence Interval 95%
0.013 to 0.087
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.086
Confidence Interval 95%
0.049 to 0.122
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.0067
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 0.051
Confidence Interval 95%
0.014 to 0.088
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 232 229 228 229
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.039  (0.014) 0.023  (0.014) 0.034  (0.014) 0.009  (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 0.0012
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 0.062
Confidence Interval 95%
0.025 to 0.100
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.073
Confidence Interval 95%
0.035 to 0.110
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.0117
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 0.048
Confidence Interval 95%
0.011 to 0.086
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 232 229 228 229
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.043  (0.014) 0.019  (0.014) 0.041  (0.014) 0.013  (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 0.0014
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 0.062
Confidence Interval 95%
0.024 to 0.099
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.084
Confidence Interval 95%
0.047 to 0.122
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.0035
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 0.056
Confidence Interval 95%
0.019 to 0.094
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 232 229 228 229
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.060  (0.014) -0.016  (0.014) -0.001  (0.014) -0.024  (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 0.0228
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%
0.006 to 0.082
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.0024
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%
0.021 to 0.097
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.0664
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 0.036
Confidence Interval 95%
-0.002 to 0.074
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.099  (0.014) 0.260  (0.014) 0.278  (0.014) 0.253  (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 0.161
Confidence Interval 95%
0.122 to 0.199
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.178
Confidence Interval 95%
0.140 to 0.216
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 0.153
Confidence Interval 95%
0.115 to 0.191
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.066  (0.014) 0.235  (0.014) 0.248  (0.014) 0.242  (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 0.168
Confidence Interval 95%
0.130 to 0.207
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 0.181
Confidence Interval 95%
0.143 to 0.220
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 0.176
Confidence Interval 95%
0.137 to 0.214
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.064  (0.014) 0.206  (0.014) 0.232  (0.014) 0.228  (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 0.141
Confidence Interval 95%
0.103 to 0.180
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 0.168
Confidence Interval 95%
0.129 to 0.207
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 0.164
Confidence Interval 95%
0.125 to 0.203
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.060  (0.015) 0.183  (0.014) 0.211  (0.014) 0.203  (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 0.123
Confidence Interval 95%
0.084 to 0.163
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 0.151
Confidence Interval 95%
0.112 to 0.191
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 0.143
Confidence Interval 95%
0.104 to 0.183
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.052  (0.015) 0.163  (0.015) 0.178  (0.015) 0.170  (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 0.112
Confidence Interval 95%
0.071 to 0.152
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 0.126
Confidence Interval 95%
0.086 to 0.166
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 0.118
Confidence Interval 95%
0.078 to 0.158
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.082  (0.025) 0.312  (0.025) 0.332  (0.025) 0.348  (0.025)
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 0.231
Confidence Interval 95%
0.162 to 0.299
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.035
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 0.250
Confidence Interval 95%
0.182 to 0.318
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.035
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 0.266
Confidence Interval 95%
0.198 to 0.334
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.035
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.027  (0.025) 0.277  (0.026) 0.276  (0.025) 0.307  (0.026)
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 0.251
Confidence Interval 95%
0.182 to 0.320
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.035
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%
0.180 to 0.318
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.035
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 0.281
Confidence Interval 95%
0.212 to 0.350
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.035
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.006  (0.026) 0.235  (0.026) 0.253  (0.026) 0.280  (0.026)
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 0.229
Confidence Interval 95%
0.159 to 0.299
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
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 0.247
Confidence Interval 95%
0.177 to 0.317
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.035
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 0.275
Confidence Interval 95%
0.205 to 0.345
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.012  (0.026) 0.212  (0.026) 0.225  (0.026) 0.253  (0.026)
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 0.199
Confidence Interval 95%
0.128 to 0.270
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
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 0.213
Confidence Interval 95%
0.142 to 0.283
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
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 0.241
Confidence Interval 95%
0.170 to 0.312
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
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 233 230 233 232
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.036  (0.027) 0.182  (0.026) 0.201  (0.026) 0.184  (0.026)
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 0.218
Confidence Interval 95%
0.146 to 0.290
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.037
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