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A Study of the Safety and Efficacy of 4 Doses of BI 1744 CL Delivered Via the Respimat in Patients With Asthma.

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: NCT01013753
Recruitment Status : Completed
First Posted : November 16, 2009
Results First Posted : June 5, 2014
Last Update Posted : June 27, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Placebo
Drug: Olodaterol (BI 1744) high
Drug: Olodaterol (BI 1744) medium
Drug: Olodaterol (BI 1744) very low
Drug: Formoterol 12 mcg
Drug: Olodaterol (BI 1744) low
Enrollment 198
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Study Total
Hide Arm/Group Description This was a randomised, double-blind, double dummy, placebo- and active-controlled, 6 treatment, 4 period incomplete crossover trial. 198 patients were assigned randomly to one of 30 treatment sequences, each sequence comprising 4 out of the 6 treatments listed: one of four doses (20 microgram (mcg), 10 mcg, 5 mcg or 2 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo. The duration of each treatment period was 4 weeks with no washout periods between treatments.
Period Title: Overall Study
Started 198 [1]
Received Placebo 125
Received Olo 2 mcg qd 121
Received Olo 5 mcg qd 130
Received Olo 10 mcg qd 127
Received Olo 20 mcg qd 124
Received Form 12 mcg Bid 125
Completed 182
Not Completed 16
Reason Not Completed
Adverse Event             8
Protocol Violation             3
Lost to Follow-up             1
Withdrawal by Subject             2
Other             2
[1]
Entered and treated
Arm/Group Title Study Total
Hide Arm/Group Description This was a randomised, double-blind, double dummy, placebo- and active-controlled, 6 treatment, 4 period incomplete crossover trial. 198 patients were assigned randomly to one of 30 treatment sequences, each sequence comprising 4 out of the 6 treatments listed: one of four doses (20 microgram (mcg), 10 mcg, 5 mcg or 2 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo. The duration of each treatment period was 4 weeks with no washout periods between treatments.
Overall Number of Baseline Participants 198
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 198 participants
45.0  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 198 participants
Female
112
  56.6%
Male
86
  43.4%
1.Primary Outcome
Title Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period
Hide Description Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all patients in the treated set for whom the baseline (pre-dose) value is available, and who have a value for the primary endpoint for at least one crossover period.
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
-0.004  (0.025) 0.135  (0.025) 0.178  (0.025) 0.201  (0.025) 0.225  (0.025) 0.164  (0.025)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.140
Confidence Interval 95%
0.097 to 0.182
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.182
Confidence Interval 95%
0.140 to 0.224
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.205
Confidence Interval 95%
0.163 to 0.248
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.229
Confidence Interval 95%
0.186 to 0.272
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.169
Confidence Interval 95%
0.126 to 0.211
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Form 12 mcg bid minus Placebo
2.Secondary Outcome
Title FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response at the End of Each Treatment Period
Hide Description Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
-0.039  (0.026) 0.124  (0.026) 0.173  (0.026) 0.194  (0.026) 0.211  (0.026) 0.145  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.163
Confidence Interval 95%
0.116 to 0.211
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.212
Confidence Interval 95%
0.166 to 0.259
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.233
Confidence Interval 95%
0.186 to 0.280
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.250
Confidence Interval 95%
0.203 to 0.298
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.184
Confidence Interval 95%
0.137 to 0.231
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Form 12 mcg bid minus Placebo
3.Secondary Outcome
Title FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response at the End of Each Treatment Period
Hide Description Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
0.031  (0.026) 0.147  (0.026) 0.183  (0.025) 0.208  (0.026) 0.238  (0.026) 0.183  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.115
Confidence Interval 95%
0.073 to 0.158
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.151
Confidence Interval 95%
0.110 to 0.193
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.177
Confidence Interval 95%
0.135 to 0.219
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.207
Confidence Interval 95%
0.164 to 0.250
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.152
Confidence Interval 95%
0.110 to 0.194
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Form 12 mcg bid minus Placebo
4.Secondary Outcome
Title Peak FEV1 Within 24 Hours Post-dose Response
Hide Description Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak FEV1 within 24 hours post dose measured following the evening trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
0.224  (0.026) 0.326  (0.027) 0.359  (0.026) 0.385  (0.027) 0.404  (0.027) 0.390  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.102
Confidence Interval 95%
0.056 to 0.148
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.135
Confidence Interval 95%
0.090 to 0.180
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.161
Confidence Interval 95%
0.116 to 0.207
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.180
Confidence Interval 95%
0.134 to 0.226
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.166
Confidence Interval 95%
0.120 to 0.211
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Form 12 mcg bid minus Placebo
5.Secondary Outcome
Title Trough FEV1 Response
Hide Description Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
0.013  (0.026) 0.116  (0.026) 0.146  (0.026) 0.182  (0.026) 0.211  (0.026) 0.115  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.103
Confidence Interval 95%
0.058 to 0.148
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.133
Confidence Interval 95%
0.088 to 0.177
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.169
Confidence Interval 95%
0.124 to 0.214
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.199
Confidence Interval 95%
0.153 to 0.244
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.103
Confidence Interval 95%
0.058 to 0.147
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Form 12 mcg bid minus Placebo
6.Secondary Outcome
Title Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
Hide Description Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h , 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
-0.047  (0.029) 0.056  (0.029) 0.109  (0.029) 0.094  (0.029) 0.122  (0.029) 0.055  (0.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.103
Confidence Interval 95%
0.052 to 0.154
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.156
Confidence Interval 95%
0.106 to 0.207
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.141
Confidence Interval 95%
0.091 to 0.192
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.169
Confidence Interval 95%
0.118 to 0.221
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.102
Confidence Interval 95%
0.051 to 0.153
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Form 12 mcg bid minus Placebo
7.Secondary Outcome
Title FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
Hide Description Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
-0.005  (0.029) 0.055  (0.029) 0.109  (0.028) 0.110  (0.029) 0.139  (0.029) 0.085  (0.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0107
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.061
Confidence Interval 95%
0.014 to 0.107
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.115
Confidence Interval 95%
0.069 to 0.160
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.115
Confidence Interval 95%
0.069 to 0.161
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.144
Confidence Interval 95%
0.098 to 0.191
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.091
Confidence Interval 95%
0.044 to 0.137
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Form 12 mcg bid minus Placebo
8.Secondary Outcome
Title FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
Hide Description Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 min, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
-0.026  (0.028) 0.056  (0.028) 0.109  (0.028) 0.102  (0.028) 0.131  (0.028) 0.070  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 mcg qd
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.082
Confidence Interval 95%
0.036 to 0.128
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.136
Confidence Interval 95%
0.090 to 0.181
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.128
Confidence Interval 95%
0.083 to 0.174
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.157
Confidence Interval 95%
0.111 to 0.203
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.097
Confidence Interval 95%
0.051 to 0.143
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Form 12 mcg bid minus Placebo
9.Secondary Outcome
Title Peak FVC Within 24 Hours Post-dose Response
Hide Description Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC within 24 hours post dose measured following the trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
0.253  (0.031) 0.300  (0.031) 0.356  (0.031) 0.342  (0.031) 0.380  (0.031) 0.326  (0.031)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0952
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.048
Confidence Interval 95%
-0.008 to 0.103
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.103
Confidence Interval 95%
0.048 to 0.158
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 0.0016
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.089
Confidence Interval 95%
0.034 to 0.145
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.127
Confidence Interval 95%
0.071 to 0.183
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0096
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.073
Confidence Interval 95%
0.018 to 0.129
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Form 12 mcg bid minus Placebo
10.Secondary Outcome
Title Trough FVC Response
Hide Description Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter
-0.022  (0.029) 0.015  (0.029) 0.069  (0.029) 0.088  (0.029) 0.107  (0.029) 0.029  (0.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1470
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.037
Confidence Interval 95%
-0.013 to 0.088
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.091
Confidence Interval 95%
0.042 to 0.141
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.025
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.110
Confidence Interval 95%
0.060 to 0.160
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.025
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.129
Confidence Interval 95%
0.078 to 0.179
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0448
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.051
Confidence Interval 95%
0.001 to 0.101
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.025
Estimation Comments Form 12 mcg bid minus Placebo
11.Secondary Outcome
Title Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response
Hide Description Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter/sec
-0.117  (0.076) 0.291  (0.077) 0.449  (0.076) 0.495  (0.077) 0.553  (0.077) 0.471  (0.076)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.408
Confidence Interval 95%
0.277 to 0.539
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.067
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.566
Confidence Interval 95%
0.438 to 0.695
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.066
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.612
Confidence Interval 95%
0.482 to 0.743
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.066
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.670
Confidence Interval 95%
0.539 to 0.801
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.067
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.588
Confidence Interval 95%
0.457 to 0.718
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.066
Estimation Comments Form 12 mcg bid minus Placebo
12.Secondary Outcome
Title PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response
Hide Description Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter/sec
0.043  (0.075) 0.380  (0.075) 0.528  (0.075) 0.575  (0.075) 0.692  (0.075) 0.594  (0.075)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.337
Confidence Interval 95%
0.213 to 0.461
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.485
Confidence Interval 95%
0.363 to 0.606
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.062
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.531
Confidence Interval 95%
0.408 to 0.655
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.648
Confidence Interval 95%
0.524 to 0.772
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.551
Confidence Interval 95%
0.428 to 0.674
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Form 12 mcg bid minus Placebo
13.Secondary Outcome
Title Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response
Hide Description Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter/sec
-0.038  (0.074) 0.336  (0.074) 0.489  (0.074) 0.534  (0.074) 0.623  (0.074) 0.532  (0.074)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.373
Confidence Interval 95%
0.253 to 0.493
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.061
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.527
Confidence Interval 95%
0.409 to 0.645
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.060
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.572
Confidence Interval 95%
0.453 to 0.692
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.061
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.660
Confidence Interval 95%
0.540 to 0.781
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.061
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.570
Confidence Interval 95%
0.451 to 0.689
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.061
Estimation Comments Form 12 mcg bid minus Placebo
14.Secondary Outcome
Title Peak PEF Within 24 Hours Post-dose Response
Hide Description Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Peak PEF within 24 hours post-dose measured following the evening trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter/sec
0.664  (0.079) 0.966  (0.079) 1.093  (0.078) 1.130  (0.079) 1.198  (0.079) 1.168  (0.079)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.302
Confidence Interval 95%
0.168 to 0.436
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.429
Confidence Interval 95%
0.297 to 0.561
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.067
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.466
Confidence Interval 95%
0.333 to 0.599
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.534
Confidence Interval 95%
0.400 to 0.669
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.504
Confidence Interval 95%
0.371 to 0.637
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Form 12 mcg bid minus Placebo
15.Secondary Outcome
Title Trough PEF Response
Hide Description Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 121 119 122
Mean (Standard Error)
Unit of Measure: Liter/sec
0.031  (0.078) 0.295  (0.078) 0.499  (0.077) 0.515  (0.078) 0.655  (0.078) 0.478  (0.078)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.264
Confidence Interval 95%
0.127 to 0.401
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.070
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.468
Confidence Interval 95%
0.333 to 0.602
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.069
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.484
Confidence Interval 95%
0.348 to 0.620
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.069
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.624
Confidence Interval 95%
0.487 to 0.761
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.070
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.447
Confidence Interval 95%
0.311 to 0.583
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.069
Estimation Comments Form 12 mcg bid minus Placebo
16.Secondary Outcome
Title Mean Pre-dose Morning PEF (PEF a.m.)
Hide Description PEF a.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 2-4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS including all patients who contributed data for this endpoint.
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 123 120 123
Mean (Standard Error)
Unit of Measure: Liter/min
361.89  (4.548) 383.90  (4.567) 390.91  (4.519) 389.78  (4.539) 394.82  (4.560) 385.42  (4.539)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 22.012
Confidence Interval 95%
14.802 to 29.223
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.671
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 29.022
Confidence Interval 95%
21.931 to 36.114
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.610
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 27.887
Confidence Interval 95%
20.755 to 35.019
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.631
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 32.935
Confidence Interval 95%
25.730 to 40.139
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.668
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 23.528
Confidence Interval 95%
16.371 to 30.686
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.644
Estimation Comments Form 12 mcg bid minus Placebo
17.Secondary Outcome
Title Mean Pre-dose Evening PEF (PEF p.m.)
Hide Description PEF p.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 2-4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS including all patients who contributed data for this endpoint.
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 123 120 123
Mean (Standard Error)
Unit of Measure: Liter/min
379.44  (4.398) 394.36  (4.418) 404.28  (4.368) 403.06  (4.389) 407.89  (4.410) 399.88  (4.389)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.920
Confidence Interval 95%
7.770 to 22.071
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.640
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 24.834
Confidence Interval 95%
17.801 to 31.866
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.580
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 23.613
Confidence Interval 95%
16.539 to 30.686
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.601
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 28.449
Confidence Interval 95%
21.305 to 35.594
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.637
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 20.439
Confidence Interval 95%
13.341 to 27.538
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.614
Estimation Comments Form 12 mcg bid minus Placebo
18.Secondary Outcome
Title PEF Daily Variability
Hide Description PEF daily variability was assessed by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). PEF daily variability is the absolute difference between the morning and the evening PEF value divided by the mean of these two values, expressed as a percent. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 2-4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS including all patients who contributed data for this endpoint.
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 122 120 123
Mean (Standard Error)
Unit of Measure: Percentage
11.688  (0.480) 9.694  (0.484) 9.593  (0.475) 9.851  (0.480) 9.899  (0.483) 10.417  (0.479)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.994
Confidence Interval 95%
-2.989 to -0.999
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.507
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.095
Confidence Interval 95%
-3.073 to -1.116
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.498
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.836
Confidence Interval 95%
-2.824 to -0.849
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.503
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 mcg qd
Comments [Not Specified]
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.789
Confidence Interval 95%
-2.783 to -0.795
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.506
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0118
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.270
Confidence Interval 95%
-2.258 to -0.283
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.503
Estimation Comments Form 12 mcg bid minus Placebo
19.Secondary Outcome
Title Mean Pre-dose Morning FEV1 (FEV1 a.m.)
Hide Description FEV1 a.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 2-4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS including all patients who contributed data for this endpoint.
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 123 120 123
Mean (Standard Error)
Unit of Measure: L
2.309  (0.028) 2.402  (0.028) 2.438  (0.028) 2.445  (0.028) 2.479  (0.028) 2.403  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.093
Confidence Interval 95%
0.045 to 0.141
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.025
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.128
Confidence Interval 95%
0.081 to 0.176
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.135
Confidence Interval 95%
0.087 to 0.183
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.169
Confidence Interval 95%
0.121 to 0.217
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.025
Estimation Comments Olo 20 mcg qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.093
Confidence Interval 95%
0.045 to 0.141
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Form 12 mcg bid minus Placebo
20.Secondary Outcome
Title Mean Pre-dose Evening FEV1 (FEV1 p.m.)
Hide Description FEV1 p.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 2-4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS including all patients who contributed data for this endpoint.
Arm/Group Title Placebo Olo 2 mcg qd Olo 5 mcg qd Olo 10 mcg qd Olo 20 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 122 119 126 123 120 123
Mean (Standard Error)
Unit of Measure: L
2.378  (0.027) 2.428  (0.027) 2.460  (0.027) 2.467  (0.027) 2.495  (0.027) 2.457  (0.027)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0362
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.050
Confidence Interval 95%
0.003 to 0.097
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 2 mcg qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.0006
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.081
Confidence Interval 95%
0.035 to 0.127
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
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 Adjusted using a mixed model with treatment, period and study baseline value as fixed effects; and patients as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.088
Confidence Interval 95%
0.042 to 0.135
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 10 mcg qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 20 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test o