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A Study to Compare the Efficacy and Safety of Different Dosings of Olodaterol Administered With the Respimat® Inhaler in Patients With Moderate to Severe 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: NCT01311661
Recruitment Status : Completed
First Posted : March 9, 2011
Results First Posted : May 1, 2014
Last Update Posted : May 1, 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 twice daily
Drug: Olodaterol low daily dose twice daily
Drug: Olodaterol medium daily dose twice daily
Drug: Olodaterol high daily dose once daily and placebo
Drug: Olodaterol medium daily dose once daily and placebo
Enrollment 206
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Study Total
Hide Arm/Group Description This was a double-blind, 3-period crossover trial. 206 patients were assigned randomly to one of 12 treatment sequences with either 5 microgram (mcg) Olodaterol (Olo) once daily (qd) and 2.5 mcg Olodaterol twice daily (bid) and placebo (6 sequences) or 10 mcg Olodaterol qd and 5 mcg Olodaterol bid and placebo (6 sequences). The duration of each treatment period was 3 weeks separated by washout periods of 2 weeks.
Period Title: Overall Study
Started 206 [1]
Received Placebo 201
Received Olo 2.5 mcg Bid 101
Received Olo 5 mcg qd 101
Received Olo 5 mcg Bid 101
Received Olo 10 mcg qd 102
Completed 199
Not Completed 7
Reason Not Completed
Adverse Event             2
Protocol Violation             3
Withdrawal by Subject             2
[1]
Entered and treated
Arm/Group Title Study Total
Hide Arm/Group Description This was a double-blind, 3-period crossover trial. 206 patients were assigned randomly to one of 12 treatment sequences with either 5 microgram (mcg) Olodaterol (Olo) once daily (qd) and 2.5 mcg Olodaterol twice daily (bid) and placebo (6 sequences) or 10 mcg Olodaterol qd and 5 mcg Olodaterol bid and placebo (6 sequences). The duration of each treatment period was 3 weeks separated by washout periods of 2 weeks.
Overall Number of Baseline Participants 206
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 206 participants
43.7  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 206 participants
Female
109
  52.9%
Male
97
  47.1%
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, 6 h, 8 h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 200 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
0.022  (0.020) 0.213  (0.024) 0.173  (0.024) 0.250  (0.024) 0.231  (0.024)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.191
Confidence Interval 95%
0.152 to 0.229
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 2.5 mcg bid 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 0.150
Confidence Interval 95%
0.111 to 0.189
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.228
Confidence Interval 95%
0.190 to 0.266
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.209
Confidence Interval 95%
0.170 to 0.247
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 10 mcg qd minus Placebo
2.Secondary Outcome
Title FEV1 Area Under Curve 0-12 Hours (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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 200 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
0.052  (0.020) 0.242  (0.024) 0.212  (0.024) 0.266  (0.024) 0.272  (0.024)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.190
Confidence Interval 95%
0.150 to 0.229
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 2.5 mcg bid 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 0.160
Confidence Interval 95%
0.121 to 0.199
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.214
Confidence Interval 95%
0.175 to 0.253
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.219
Confidence Interval 95%
0.181 to 0.258
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 10 mcg qd minus Placebo
3.Secondary Outcome
Title FEV1 Area Under Curve 12-24 Hours (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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
-0.010  (0.020) 0.186  (0.025) 0.135  (0.025) 0.233  (0.025) 0.189  (0.025)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.196
Confidence Interval 95%
0.153 to 0.238
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 2.5 mcg bid 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 0.144
Confidence Interval 95%
0.102 to 0.187
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.242
Confidence Interval 95%
0.200 to 0.285
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.198
Confidence Interval 95%
0.156 to 0.241
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd 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 morning trial drug inhalation at the end of each 3 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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
0.227  (0.021) 0.410  (0.027) 0.380  (0.027) 0.449  (0.027) 0.437  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.183
Confidence Interval 95%
0.138 to 0.228
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 2.5 mcg bid 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 0.153
Confidence Interval 95%
0.108 to 0.198
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 5 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 0.222
Confidence Interval 95%
0.177 to 0.267
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.210
Confidence Interval 95%
0.165 to 0.255
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 10 mcg qd 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 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 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 morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
0.033  (0.022) 0.189  (0.027) 0.134  (0.027) 0.229  (0.027) 0.205  (0.027)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.156
Confidence Interval 95%
0.109 to 0.203
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 2.5 mcg bid 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 0.101
Confidence Interval 95%
0.054 to 0.148
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 5 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 0.196
Confidence Interval 95%
0.149 to 0.243
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.172
Confidence Interval 95%
0.125 to 0.219
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 10 mcg qd 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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 200 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
-0.004  (0.022) 0.132  (0.027) 0.119  (0.027) 0.138  (0.026) 0.143  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.136
Confidence Interval 95%
0.091 to 0.180
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Olo 2.5 mcg bid 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 0.122
Confidence Interval 95%
0.078 to 0.167
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 5 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 0.142
Confidence Interval 95%
0.098 to 0.186
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.147
Confidence Interval 95%
0.103 to 0.191
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd 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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
-0.056  (0.023) 0.102  (0.028) 0.081  (0.028) 0.114  (0.028) 0.079  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.158
Confidence Interval 95%
0.110 to 0.206
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 2.5 mcg bid 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 0.137
Confidence Interval 95%
0.090 to 0.185
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 5 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 0.170
Confidence Interval 95%
0.123 to 0.218
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.182
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Olo 10 mcg qd 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 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 200 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
-0.029  (0.021) 0.116  (0.026) 0.099  (0.026) 0.127  (0.026) 0.111  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.145
Confidence Interval 95%
0.102 to 0.188
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 2.5 mcg bid 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%
0.085 to 0.171
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.156
Confidence Interval 95%
0.113 to 0.198
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.140
Confidence Interval 95%
0.098 to 0.182
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments Olo 10 mcg qd 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 morning trial drug inhalation at the end of each 3 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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
0.246  (0.024) 0.382  (0.030) 0.371  (0.030) 0.390  (0.030) 0.373  (0.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.136
Confidence Interval 95%
0.084 to 0.187
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 2.5 mcg bid 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 0.124
Confidence Interval 95%
0.073 to 0.176
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 5 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 0.144
Confidence Interval 95%
0.093 to 0.195
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.126
Confidence Interval 95%
0.075 to 0.177
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Olo 10 mcg qd 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 FVC values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 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 morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter
-0.013  (0.024) 0.096  (0.031) 0.079  (0.031) 0.105  (0.031) 0.098  (0.031)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.110
Confidence Interval 95%
0.055 to 0.165
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 2.5 mcg bid 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 0.0010
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 0.092
Confidence Interval 95%
0.037 to 0.147
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 5 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 0.118
Confidence Interval 95%
0.063 to 0.172
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.111
Confidence Interval 95%
0.057 to 0.166
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 10 mcg qd 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, 6 h, 8h, 10 h, 11 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 200 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter/sec
0.101  (0.060) 0.730  (0.075) 0.703  (0.075) 0.732  (0.074) 0.787  (0.074)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.629
Confidence Interval 95%
0.500 to 0.757
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.065
Estimation Comments Olo 2.5 mcg bid 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 0.601
Confidence Interval 95%
0.473 to 0.730
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.065
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.631
Confidence Interval 95%
0.503 to 0.758
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.065
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.685
Confidence Interval 95%
0.558 to 0.813
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.065
Estimation Comments Olo 10 mcg qd 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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter/sec
-0.135  (0.061) 0.530  (0.077) 0.430  (0.076) 0.567  (0.076) 0.464  (0.076)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.665
Confidence Interval 95%
0.532 to 0.799
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Olo 2.5 mcg bid 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 0.564
Confidence Interval 95%
0.431 to 0.698
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.702
Confidence Interval 95%
0.569 to 0.835
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.599
Confidence Interval 95%
0.467 to 0.732
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.067
Estimation Comments Olo 10 mcg qd 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 -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 200 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter/sec
-0.014  (0.059) 0.627  (0.073) 0.563  (0.073) 0.653  (0.073) 0.629  (0.073)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.641
Confidence Interval 95%
0.516 to 0.765
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Olo 2.5 mcg bid 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 0.577
Confidence Interval 95%
0.453 to 0.701
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.667
Confidence Interval 95%
0.544 to 0.790
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.643
Confidence Interval 95%
0.519 to 0.766
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Olo 10 mcg qd 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 morning trial drug inhalation at the end of each 3 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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter/sec
0.663  (0.068) 1.254  (0.087) 1.185  (0.087) 1.257  (0.086) 1.286  (0.086)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.591
Confidence Interval 95%
0.436 to 0.746
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.079
Estimation Comments Olo 2.5 mcg bid 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 0.522
Confidence Interval 95%
0.366 to 0.677
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.079
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.594
Confidence Interval 95%
0.439 to 0.749
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.079
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.623
Confidence Interval 95%
0.468 to 0.777
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.079
Estimation Comments Olo 10 mcg qd 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 PEF values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 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 morning dose after 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 99 100 101
Mean (Standard Error)
Unit of Measure: Liter/sec
-0.009  (0.062) 0.520  (0.078) 0.401  (0.078) 0.594  (0.077) 0.472  (0.077)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 0.529
Confidence Interval 95%
0.396 to 0.662
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Olo 2.5 mcg bid 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 0.410
Confidence Interval 95%
0.277 to 0.543
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.068
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 0.603
Confidence Interval 95%
0.471 to 0.736
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.067
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.481
Confidence Interval 95%
0.349 to 0.613
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.067
Estimation Comments Olo 10 mcg qd 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 AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Mean (Standard Error)
Unit of Measure: Liter/min
395.36  (2.857) 428.32  (3.586) 427.99  (3.575) 427.02  (3.562) 424.26  (3.562)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 32.957
Confidence Interval 95%
26.709 to 39.206
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.180
Estimation Comments Olo 2.5 mcg bid 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 32.632
Confidence Interval 95%
26.409 to 38.855
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.167
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 31.660
Confidence Interval 95%
25.448 to 37.872
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.161
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 28.895
Confidence Interval 95%
22.683 to 35.107
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.161
Estimation Comments Olo 10 mcg qd 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 AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Mean (Standard Error)
Unit of Measure: Liter/min
409.93  (2.717) 438.80  (3.418) 441.98  (3.407) 441.74  (3.395) 443.25  (3.395)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 28.870
Confidence Interval 95%
22.884 to 34.856
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.046
Estimation Comments Olo 2.5 mcg bid 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 32.056
Confidence Interval 95%
26.094 to 38.018
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.034
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 31.816
Confidence Interval 95%
25.864 to 37.767
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.028
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 33.327
Confidence Interval 95%
27.375 to 39.278
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.028
Estimation Comments Olo 10 mcg qd minus Placebo
18.Secondary Outcome
Title PEF Daily Variability
Hide Description PEF daily variability was assessed by patients at home using the AM3 device (overall means obtained during each period of randomised treatment 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 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Mean (Standard Error)
Unit of Measure: Percentage
10.157  (0.288) 8.576  (0.371) 8.732  (0.369) 8.419  (0.368) 9.468  (0.368)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 -1.581
Confidence Interval 95%
-2.262 to -0.900
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.346
Estimation Comments Olo 2.5 mcg bid 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 -1.426
Confidence Interval 95%
-2.104 to -0.748
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.345
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 -1.738
Confidence Interval 95%
-2.415 to -1.062
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.344
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 0.0458
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 -0.689
Confidence Interval 95%
-1.366 to -0.013
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.344
Estimation Comments Olo 10 mcg qd 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 AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Mean (Standard Error)
Unit of Measure: mL
2425.1  (17.870) 2598.5  (22.276) 2580.2  (22.208) 2574.3  (22.133) 2575.5  (22.133)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 173.391
Confidence Interval 95%
135.099 to 211.682
Parameter Dispersion
Type: Standard Error of the mean
Value: 19.484
Estimation Comments Olo 2.5 mcg bid 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 155.097
Confidence Interval 95%
116.961 to 193.234
Parameter Dispersion
Type: Standard Error of the mean
Value: 19.406
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 149.268
Confidence Interval 95%
111.204 to 187.333
Parameter Dispersion
Type: Standard Error of the mean
Value: 19.369
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 150.441
Confidence Interval 95%
112.377 to 188.505
Parameter Dispersion
Type: Standard Error of the mean
Value: 19.369
Estimation Comments Olo 10 mcg qd 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 AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Mean (Standard Error)
Unit of Measure: mL
2474.3  (17.692) 2616.6  (21.949) 2606.5  (21.884) 2616.5  (21.810) 2631.7  (21.809)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 142.251
Confidence Interval 95%
104.916 to 179.586
Parameter Dispersion
Type: Standard Error of the mean
Value: 18.997
Estimation Comments Olo 2.5 mcg bid 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 132.138
Confidence Interval 95%
94.954 to 169.322
Parameter Dispersion
Type: Standard Error of the mean
Value: 18.920
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 142.136
Confidence Interval 95%
105.021 to 179.251
Parameter Dispersion
Type: Standard Error of the mean
Value: 18.885
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 157.306
Confidence Interval 95%
120.192 to 194.420
Parameter Dispersion
Type: Standard Error of the mean
Value: 18.885
Estimation Comments Olo 10 mcg qd minus Placebo
21.Secondary Outcome
Title Mean Number of Puffs of Rescue Medication During the Whole Day
Hide Description Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM3 device (overall mean number obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Mean (Standard Error)
Unit of Measure: Puffs
1.665  (0.091) 1.110  (0.120) 1.028  (0.119) 1.077  (0.119) 1.119  (0.119)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 -0.554
Confidence Interval 95%
-0.780 to -0.329
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.115
Estimation Comments Olo 2.5 mcg bid 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 -0.637
Confidence Interval 95%
-0.862 to -0.412
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.114
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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%
-0.813 to -0.364
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.114
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 -0.546
Confidence Interval 95%
-0.770 to -0.322
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.114
Estimation Comments Olo 10 mcg qd minus Placebo
22.Secondary Outcome
Title Percentage of Asthma Symptom Free Days
Hide Description Percentage of asthma-symptom free days of each treatment period was calculated as the number of symptom-free days divided by the number of days on treatment multiplied by 100. A symptom-free day was defined as a day in which no asthma symptoms were recorded, no rescue medication was recorded, activities during the day were not at all limited due to asthma, no shortness of breath during the day was recorded, no wheezing or coughing during the day and no night-time awakenings due to asthma were recorded. Assessed by patients at home using the AM3 device.
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Mean (Standard Error)
Unit of Measure: Percentage of asthma symptom free days
23.630  (2.235) 33.929  (3.554) 36.306  (3.644) 28.844  (3.271) 28.049  (3.368)
23.Secondary Outcome
Title Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
Hide Description Assessed by patients at home using the AM3 device during each period of randomised treatment.
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Measure Type: Number
Unit of Measure: Number of patients
Did not wake up 93 50 53 44 47
Woke up once 67 31 36 41 32
Woke up 2-5 times 36 18 10 14 19
Woke up > 5 times 5 0 1 0 2
Was awake all night 0 0 0 2 1
24.Secondary Outcome
Title Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
Hide Description Assessed by patients at home using the AM3 device during each period of randomised treatment .
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Measure Type: Number
Unit of Measure: Number of patients
No asthma symptoms 31 24 27 18 20
Mild asthma symptoms 66 45 42 42 41
Moderate asthma symptoms 85 25 27 36 37
Severe asthma symptoms 18 4 3 4 2
Very severe asthma symptoms 1 1 1 1 1
25.Secondary Outcome
Title Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
Hide Description Assessed by patients at home using the AM3 device during each period of randomised treatment.
Time Frame 0-3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Measure Type: Number
Unit of Measure: Number of patients
No asthma symptoms 39 32 29 21 21
Mild asthma symptoms 76 35 38 48 40
Moderate asthma symptoms 74 26 32 29 35
Severe asthma symptoms 9 4 1 2 3
Very severe asthma symptoms 3 2 0 1 2
26.Secondary Outcome
Title Total Asthma Control Questionnaire (ACQ) Score
Hide Description Control of asthma as assessed by the ACQ at the end of each 3-week treatment period.The ACQ contains 7 questions, each question has a 7 point scale from 0 (no symptoms) till 6 (highest intensity). Total score was defined as the sum of all items divided by the number of items.
Time Frame 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 99 100 101 101
Mean (Standard Error)
Unit of Measure: Units on a scale
1.613  (0.040) 1.256  (0.053) 1.317  (0.053) 1.312  (0.053) 1.311  (0.053)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 2.5 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 -0.357
Confidence Interval 95%
-0.461 to -0.253
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.053
Estimation Comments Olo 2.5 mcg bid 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 -0.296
Confidence Interval 95%
-0.400 to -0.192
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.053
Estimation Comments Olo 5 mcg qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 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 -0.301
Confidence Interval 95%
-0.405 to -0.198
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.053
Estimation Comments Olo 5 mcg bid minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
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 -0.302
Confidence Interval 95%
-0.405 to -0.198
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.053
Estimation Comments Olo 10 mcg qd minus Placebo
27.Secondary Outcome
Title Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Hide Description Clinical relevant abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.
Time Frame 3 weeks + 12 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Placebo Olo 2.5 mcg Bid Olo 5 mcg qd Olo 5 mcg Bid Olo 10 mcg qd
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).
Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Olodaterol 5 mcg bid delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Overall Number of Participants Analyzed 201 101 101 101 102
Measure Type: Number
Unit of Measure: Participants
Atrioventricular block first degree 0 0 1 0 0
Sinus tachycardia 1 0 0 0 0
Aspartate aminotransferase increased 0 0 0 0 1
Blood creatinine increased 0 0 1 0 0
Blood glucose increased 0 0 0 0 1
Blood urea abnormal 0 0 1 0 0
Gamma-glutamyltransferase increased 0 0 0 0 1
Blood creatine phosphokinase increased 1 0 0 0 0
Blood urine present 1 0 0 0