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Characterization of 24 Hour Spirometry Profiles of Inhaled BI 1744 CL and Inhaled Foradil in Patients With Chronic Obstructive Pulmonary Disease

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: NCT00931385
Recruitment Status : Completed
First Posted : July 2, 2009
Results First Posted : July 1, 2014
Last Update Posted : July 1, 2014
Sponsor:
Information provided by:
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: BI 1744
Drug: bi1744
Drug: Placebo
Drug: Foradil
Enrollment 99
Recruitment Details  
Pre-assignment Details This was a randomised, double-blind, double-dummy, placebo-controlled, 4-way crossover trial. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments.
Arm/Group Title Olo 5mcg / Foradil 12mcg / Placebo / Olo 10mcg Foradil 12mcg / Olo 10mcg / Olo 5mcg / Placebo Olo 10mcg / Placebo / Foradil 12mcg / Olo 5mcg Placebo / Olo 5mcg / Olo 10mcg / Foradil 12mcg
Hide Arm/Group Description Patients were administered Olodaterol 5 mcg qd in the first period, Foradil 12 mcg bid in the second period, matching Placebo in the third period and Olodaterol 10 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler. Patients were administered Foradil 12 mcg bid in the first period, Olodaterol 10 mcg qd in the second period, Olodaterol 5 mcg qd in the third period and matching Placebo in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler. Patients were administered Olodaterol 10 mcg qd in the first period, matching Placebo in the second period, Foradil 12 mcg bid in the third period and Olodaterol 5 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler. Patients were administered matching Placebo in the first period, Olodaterol 5 mcg qd in the second period, Olodaterol 10 mcg qd in the third period and Foradil 12 mcg bid in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.
Period Title: Overall Study
Started 25 23 25 26
Completed 23 21 24 21
Not Completed 2 2 1 5
Reason Not Completed
Adverse Event             2             1             0             3
Protocol Violation             0             0             1             0
Withdrawal by Subject             0             1             0             1
Lost to Follow-up             0             0             0             1
Arm/Group Title Study Total
Hide Arm/Group Description Total number of patients treated in the study. This was a randomised, double-blind, double dummy, placebo- and active-controlled, 4 way crossover trial. 99 patients were assigned randomly to one of 4 treatment sequences in which they received each of 4 treatments, two doses (5 microgram (mcg) or 10 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo delivered by Respimat Inhaler or Aerolizer Inhaler. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments.
Overall Number of Baseline Participants 99
Hide Baseline Analysis Population Description
Treated set, i.e., all treated patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 99 participants
61.8  (8.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants
Female
47
  47.5%
Male
52
  52.5%
1.Primary Outcome
Title FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment
Hide Description Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. 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) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS). FAS is defined as all patients with the baseline (pre-dose) data and any evaluable post-dosing data for the first co-primary endpoint FEV1AUC 0-12h.
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.060  (0.020) 0.088  (0.021) 0.088  (0.021) 0.081  (0.021)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.148
Confidence Interval 95%
0.113 to 0.183
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.148
Confidence Interval 95%
0.113 to 0.183
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.141
Confidence Interval 95%
0.106 to 0.177
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
Estimation Comments Form 12 mcg bid minus Placebo
2.Primary Outcome
Title FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment
Hide Description Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. 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 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.123  (0.021) -0.014  (0.022) 0.004  (0.022) 0.049  (0.022)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.109
Confidence Interval 95%
0.073 to 0.146
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.127
Confidence Interval 95%
0.091 to 0.164
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.172
Confidence Interval 95%
0.135 to 0.209
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
Estimation Comments Form 12 mcg bid minus Placebo
3.Secondary Outcome
Title Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment
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 using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.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 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.092  (0.020) 0.037  (0.021) 0.046  (0.021) 0.065  (0.021)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.128
Confidence Interval 95%
0.094 to 0.163
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.017
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.137
Confidence Interval 95%
0.103 to 0.172
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.017
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.156
Confidence Interval 95%
0.122 to 0.191
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.018
Estimation Comments Form 12 mcg bid minus Placebo
4.Secondary Outcome
Title Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment
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 using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-3h was calculated from 0-3hours post-dose using the trapezoidal rule, divided by the observation time (3 h) to report in litres.
Time Frame 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the last am dose after six weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.030  (0.020) 0.134  (0.021) 0.135  (0.021) 0.168  (0.021)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.164
Confidence Interval 95%
0.126 to 0.201
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.164
Confidence Interval 95%
0.127 to 0.202
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.198
Confidence Interval 95%
0.160 to 0.236
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.019
Estimation Comments Form 12 mcg bid minus Placebo
5.Secondary Outcome
Title Peak FEV1 (0-3h) Response
Hide Description Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values at the randomisation visit. Peak (0-3h) values were obtained within 0 - 3 hours after the last am dose after six weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.
Time Frame Baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.034  (0.022) 0.208  (0.022) 0.200  (0.022) 0.251  (0.022)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.174
Confidence Interval 95%
0.135 to 0.214
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.166
Confidence Interval 95%
0.127 to 0.206
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.218
Confidence Interval 95%
0.178 to 0.257
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.020
Estimation Comments Form 12 mcg bid minus Placebo
6.Secondary Outcome
Title Trough FEV1 Response
Hide Description Response was defined as change from baseline. Study baseline trough FEV1 was defined as the mean of the available pre-dose trough FEV1 values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.
Time Frame Baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.093  (0.023) 0.012  (0.024) 0.020  (0.024) 0.040  (0.024)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.106
Confidence Interval 95%
0.064 to 0.147
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.113
Confidence Interval 95%
0.072 to 0.155
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.133
Confidence Interval 95%
0.092 to 0.175
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.021
Estimation Comments Form 12 mcg bid minus Placebo
7.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 using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time Frame 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.086  (0.036) 0.139  (0.036) 0.142  (0.036) 0.117  (0.036)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.226
Confidence Interval 95%
0.167 to 0.284
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.229
Confidence Interval 95%
0.170 to 0.287
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.203
Confidence Interval 95%
0.144 to 0.262
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Form 12 mcg bid minus Placebo
8.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 using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time Frame 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.164  (0.036) -0.016  (0.037) 0.008  (0.037) 0.088  (0.037)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.147
Confidence Interval 95%
0.087 to 0.207
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.171
Confidence Interval 95%
0.112 to 0.231
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.251
Confidence Interval 95%
0.191 to 0.311
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Form 12 mcg bid minus Placebo
9.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 using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time Frame 1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.125  (0.035) 0.061  (0.035) 0.075  (0.035) 0.102  (0.035)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.186
Confidence Interval 95%
0.132 to 0.241
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.200
Confidence Interval 95%
0.145 to 0.254
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.227
Confidence Interval 95%
0.172 to 0.282
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.028
Estimation Comments Form 12 mcg bid minus Placebo
10.Secondary Outcome
Title Peak FVC (0-3h) Response
Hide Description Response was defined as change from baseline. Study baseline peak FVC was defined as the mean of the available pre-dose peak FVC values at the randomisation visit. Peak FVC (0-3h) was obtained within 0 - 3 hours after the last am dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.
Time Frame Baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.107  (0.038) 0.368  (0.039) 0.360  (0.039) 0.410  (0.039)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.261
Confidence Interval 95%
0.191 to 0.330
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.035
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.252
Confidence Interval 95%
0.183 to 0.322
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.302
Confidence Interval 95%
0.232 to 0.372
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
Estimation Comments Form 12 mcg bid minus Placebo
11.Secondary Outcome
Title Trough FVC Response
Hide Description Response was defined as change from baseline. Study baseline trough FVC was defined as the mean of the available pre-dose trough FVC values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.
Time Frame Baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Olo 5 mcg qd Olo 10 mcg qd Form 12 mcg Bid
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 93 92 91 90
Least Squares Mean (Standard Error)
Unit of Measure: Liter
-0.117  (0.039) 0.037  (0.040) 0.037  (0.040) 0.066  (0.040)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 5 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.154
Confidence Interval 95%
0.087 to 0.221
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.034
Estimation Comments Olo 5 mcg qd minus Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Olo 10 mcg qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.154
Confidence Interval 95%
0.086 to 0.221
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.034
Estimation Comments Olo 10 mcg qd minus Placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Form 12 mcg Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.183
Confidence Interval 95%
0.115 to 0.250
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.034
Estimation Comments Form 12 mcg bid minus Placebo
12.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 worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations).
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set.
Arm/Group Title Placebo Olo 5 mcg Olo 10 mcg Form 12 mcg
Hide Arm/Group Description:
Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Number of Participants Analyzed 96 95 92 93
Measure Type: Number
Unit of Measure: participants
Heart rate increased 0 1 0 0
Tachycardia 0 0 1 0
Time Frame 6 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Olo 5 mcg Olo 10 mcg Form 12 mcg
Hide Arm/Group Description Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler. Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler. Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler. Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
All-Cause Mortality
Placebo Olo 5 mcg Olo 10 mcg Form 12 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo Olo 5 mcg Olo 10 mcg Form 12 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/96 (4.17%)   4/95 (4.21%)   2/92 (2.17%)   1/93 (1.08%) 
Cardiac disorders         
Atrial fibrillation  1  1/96 (1.04%)  0/95 (0.00%)  0/92 (0.00%)  0/93 (0.00%) 
Cardio-respiratory arrest  1  0/96 (0.00%)  1/95 (1.05%)  0/92 (0.00%)  0/93 (0.00%) 
Myocardial infarction  1  0/96 (0.00%)  0/95 (0.00%)  1/92 (1.09%)  1/93 (1.08%) 
Infections and infestations         
Pneumonia  1  0/96 (0.00%)  1/95 (1.05%)  0/92 (0.00%)  0/93 (0.00%) 
Musculoskeletal and connective tissue disorders         
Lumbar spinal stenosis  1  0/96 (0.00%)  0/95 (0.00%)  1/92 (1.09%)  0/93 (0.00%) 
Nervous system disorders         
Cerebrovascular accident  1  1/96 (1.04%)  0/95 (0.00%)  0/92 (0.00%)  0/93 (0.00%) 
Radiculopathy  1  0/96 (0.00%)  0/95 (0.00%)  1/92 (1.09%)  0/93 (0.00%) 
Psychiatric disorders         
Depression  1  0/96 (0.00%)  1/95 (1.05%)  0/92 (0.00%)  0/93 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease  1  2/96 (2.08%)  1/95 (1.05%)  0/92 (0.00%)  1/93 (1.08%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Olo 5 mcg Olo 10 mcg Form 12 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/96 (5.21%)   4/95 (4.21%)   1/92 (1.09%)   3/93 (3.23%) 
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease  1  5/96 (5.21%)  4/95 (4.21%)  1/92 (1.09%)  3/93 (3.23%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00931385    
Other Study ID Numbers: 1222.24
First Submitted: July 1, 2009
First Posted: July 2, 2009
Results First Submitted: March 28, 2014
Results First Posted: July 1, 2014
Last Update Posted: July 1, 2014