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Trial record 8 of 10795 for:    Placebo AND once

Randomised, Double- Blind, Cross-over Efficacy and Safety Comparison of Three Different Doses of Tiotropium Administered Once Daily Versus Placebo in Patients With Moderate Persistent Asthma.

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ClinicalTrials.gov Identifier: NCT01233284
Recruitment Status : Completed
First Posted : November 3, 2010
Results First Posted : January 21, 2013
Last Update Posted : December 24, 2013
Sponsor:
Collaborator:
Pfizer
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: tiotropium bromide 2.5µg once daily
Drug: Tiotropium matching Placebo once daily
Drug: tiotropium bromide high dose once daily
Drug: tiotropium bromide 1.25µg once daily
Enrollment 149
Recruitment Details A total of 149 patients were randomised and treated, 141 patients completed the trial.
Pre-assignment Details Randomised, double-blind, placebo controlled, cross-over design without washout phase between the four periods. Patients were randomized to one of the 4 sequences (ABCD, DCBA, BDAC, CADB). For one patient treatment 2 and treatment 3 were interchanged (resulting sequence DBCA).
Arm/Group Title Tio R5 Once Daily(qd)/Tio R1.25 qd/Placebo/Tio R2.5 qd Tio R2.5 qd/Placebo/Tio R1.25 qd/Tio R5 qd Tio R1.25 qd/Tio R2.5 qd/Tio R5 qd/Placebo Placebo/Tio R5 qd/Tio R2.5 qd/Tio R1.25 qd Placebo/Tio R2.5 qd/Tio R5 qd/Tio R1.25 qd
Hide Arm/Group Description Patients treated with Tiotropium 5 mcg in period 1 (evening), with Tiotropium 1.25 mcg in period 2 (evening), with a matching Placebo in period 3 (evening) and with Tiotropium 2.5 mcg in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to inhaled corticosteroids (ICS). No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks. Patients treated with Tiotropium 2.5 mcg in period 1 (evening), with a matching Placebo in period 2 (evening), with Tiotropium 1.25 mcg in period 3 (evening) and with Tiotropium 5 mcg in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to ICS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks. Patients treated with Tiotropium 1.25 mcg in period 1 (evening), with Tiotropium 2.5 mcg in period 2 (evening), with Tiotropium 5 mcg in period 3 (evening) and with a matching placebo in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to inhaled corticosteroid ICS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks. Patients treated with a matching Placebo in period 1 (evening), with Tiotropium 5 mcg in period 2 (evening), with Tiotropium 2.5 mcg in period 3 (evening) and with Tiotropium 1.25 mcg in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to ICS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks. Patient treated with a matching Placebo in period 1 (evening), with Tiotropium 2.5 mcg in period 2 (evening), with Tiotropium 5 mcg in period 3 (evening) and with Tiotropium 1.25 mcg in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to ICS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
Period Title: Period 1 (4 Weeks)
Started 37 38 38 35 1
Completed 36 37 37 35 1
Not Completed 1 1 1 0 0
Reason Not Completed
Lost to Follow-up             1             0             0             0             0
Withdrawal by Subject             0             1             0             0             0
Other             0             0             1             0             0
Period Title: Period 2 (4 Weeks)
Started 36 37 37 35 1
Completed 36 37 36 35 1
Not Completed 0 0 1 0 0
Reason Not Completed
Withdrawal by Subject             0             0             1             0             0
Period Title: Period 3 (4 Weeks)
Started 36 37 36 35 1
Completed 36 37 35 34 1
Not Completed 0 0 1 1 0
Reason Not Completed
Withdrawal by Subject             0             0             1             0             0
Other             0             0             0             1             0
Period Title: Period 4 (4 Weeks)
Started 36 37 35 34 1
Completed 36 36 35 33 1
Not Completed 0 1 0 1 0
Reason Not Completed
Adverse Event             0             1             0             0             0
Lost to Follow-up             0             0             0             1             0
Arm/Group Title Baseline Total
Hide Arm/Group Description Total number of patients randomised and treated in the study.
Overall Number of Baseline Participants 149
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 149 participants
49.3  (13.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 149 participants
Female
82
  55.0%
Male
67
  45.0%
1.Primary Outcome
Title Forced Expiratory Volume in One Second (FEV1) Peak Within 0-3 Hours Post-dose Response
Hide Description Mixed model repeated measurement (MMRM) results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) reduced to patients with non-missing FEV1 data. The FAS is defined as patients randomised, treated, with baseline data and at least one on-treatment efficacy measurement after 4 weeks on treatment within a period.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre
0.116  (0.027) 0.255  (0.027) 0.244  (0.027) 0.304  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.138
Confidence Interval 95%
0.090 to 0.186
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.128
Confidence Interval 95%
0.080 to 0.176
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.188
Confidence Interval 95%
0.140 to 0.236
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Tio R5 qd minus Placebo
2.Secondary Outcome
Title Trough FEV1 Response
Hide Description MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Trough FEV1 was measured just prior to the last administration of randomised treatment.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing FEV1 data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre
0.006  (0.027) 0.131  (0.027) 0.138  (0.027) 0.149  (0.027)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.125
Confidence Interval 95%
0.078 to 0.173
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.132
Confidence Interval 95%
0.084 to 0.179
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.143
Confidence Interval 95%
0.096 to 0.191
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.024
Estimation Comments Tio R5 qd minus Placebo
3.Secondary Outcome
Title FEV1 Area Under the Curve 0-3 Hours (AUC0-3h) Response
Hide Description MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC0-3h was calculated using the trapezoidal rule divided by the observation time (3 hours) to report in litres.
Time Frame 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing FEV1 data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre
0.025  (0.027) 0.154  (0.027) 0.152  (0.027) 0.203  (0.027)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.129
Confidence Interval 95%
0.083 to 0.175
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.127
Confidence Interval 95%
0.081 to 0.172
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.178
Confidence Interval 95%
0.132 to 0.224
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.023
Estimation Comments Tio R5 qd minus Placebo
4.Secondary Outcome
Title Forced Vital Capacity (FVC) Peak Within 0-3 Hours Post-dose Response
Hide Description MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Time Frame 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing FVC data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre
0.092  (0.034) 0.171  (0.034) 0.163  (0.034) 0.229  (0.034)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.079
Confidence Interval 95%
0.026 to 0.132
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.027
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0087
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.071
Confidence Interval 95%
0.018 to 0.124
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.027
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.137
Confidence Interval 95%
0.085 to 0.190
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.027
Estimation Comments Tio R5 qd minus Placebo
5.Secondary Outcome
Title Trough FVC Response
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Trough FVC was measured just prior to the last administration of randomised treatment.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing FVC data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre
0.004  (0.035) 0.058  (0.035) 0.076  (0.035) 0.102  (0.035)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0732
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.054
Confidence Interval 95%
-0.005 to 0.113
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0177
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.072
Confidence Interval 95%
0.012 to 0.131
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.098
Confidence Interval 95%
0.039 to 0.157
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.030
Estimation Comments Tio R5 qd minus Placebo
6.Secondary Outcome
Title FVC AUC0-3h Response
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. FVC AUC0-3h was calculated using the trapezoidal rule divided by the observation time (3 hours) to report in litres.
Time Frame 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing FVC data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre
-0.028  (0.034) 0.036  (0.034) 0.047  (0.034) 0.110  (0.034)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0149
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.064
Confidence Interval 95%
0.013 to 0.115
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0043
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.075
Confidence Interval 95%
0.024 to 0.126
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.138
Confidence Interval 95%
0.086 to 0.189
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.026
Estimation Comments Tio R5 qd minus Placebo
7.Secondary Outcome
Title Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing FEV1 data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre
Timepoint -0:10 0.006  (0.027) 0.131  (0.027) 0.138  (0.027) 0.149  (0.027)
Timepoint 0:30 0.029  (0.028) 0.160  (0.028) 0.163  (0.028) 0.209  (0.028)
Timepoint 1:00 0.026  (0.029) 0.148  (0.029) 0.156  (0.029) 0.205  (0.029)
Timepoint 2:00 0.033  (0.029) 0.158  (0.029) 0.149  (0.029) 0.218  (0.029)
Timepoint 3:00 0.013  (0.029) 0.160  (0.029) 0.148  (0.029) 0.191  (0.029)
8.Secondary Outcome
Title Individual FVC Over Time (at Each Timepoint at Visits) Response
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing FVC data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre
Timepoint -0:10 0.004  (0.035) 0.058  (0.035) 0.076  (0.035) 0.102  (0.035)
Timepoint 0:30 -0.028  (0.035) 0.042  (0.035) 0.060  (0.035) 0.124  (0.035)
Timepoint 1:00 -0.031  (0.036) 0.024  (0.036) 0.041  (0.036) 0.112  (0.036)
Timepoint 2:00 -0.022  (0.036) 0.037  (0.036) 0.045  (0.036) 0.119  (0.036)
Timepoint 3:00 -0.050  (0.036) 0.036  (0.036) 0.033  (0.036) 0.078  (0.036)
9.Secondary Outcome
Title Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing PEF data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 144 144 144 143
Mean (Standard Error)
Unit of Measure: Litre/min
Timepoint -0:10 11.038  (4.804) 30.567  (4.802) 33.903  (4.804) 34.787  (4.812)
Timepoint 0:30 8.235  (4.949) 32.163  (4.947) 37.149  (4.949) 39.325  (4.957)
Timepoint 1:00 6.095  (5.074) 34.070  (5.072) 36.851  (5.074) 41.260  (5.082)
Timepoint 2:00 7.237  (5.039) 34.544  (5.037) 36.972  (5.039) 42.694  (5.047)
Timepoint 3:00 5.046  (5.024) 34.620  (5.022) 37.283  (5.024) 40.624  (5.033)
10.Secondary Outcome
Title Mean Pre-dose Morning PEF (PEF a.m.) Response During the Last Week on Treatment
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing morning PEF data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 142 146 146 144
Mean (Standard Error)
Unit of Measure: Litre/min
4.395  (4.573) 22.944  (4.543) 22.290  (4.543) 25.241  (4.559)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 18.550
Confidence Interval 95%
11.204 to 25.895
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.737
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 17.895
Confidence Interval 95%
10.550 to 25.240
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.737
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 20.846
Confidence Interval 95%
13.497 to 28.195
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.739
Estimation Comments Tio R5 qd minus Placebo
11.Secondary Outcome
Title Mean Pre-dose Evening PEF (PEF p.m.) Response During the Last Week on Treatment
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing evening PEF data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 142 146 146 144
Mean (Standard Error)
Unit of Measure: Litre/min
3.833  (4.363) 25.084  (4.331) 18.410  (4.331) 25.414  (4.348)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 21.251
Confidence Interval 95%
13.840 to 28.662
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.770
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.577
Confidence Interval 95%
7.166 to 21.988
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.770
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 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 MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 21.581
Confidence Interval 95%
14.166 to 28.997
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.773
Estimation Comments Tio R5 qd minus Placebo
12.Secondary Outcome
Title PEF Variability Response (Last Week on Treatment)
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. PEF variability is the absolute difference between morning and evening PEF value divided by the mean of these two values, expressed as a percent . Weekly means obtained during the last week of each period of randomised treatment will be compared.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing morning and evening PEF data.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 142 146 146 144
Mean (Standard Error)
Unit of Measure: Percentage of the mean daily PEF
-0.171  (0.615) -0.285  (0.609) -0.711  (0.609) -0.248  (0.612)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8574
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.114
Confidence Interval 95%
-1.363 to 1.134
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.635
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3954
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.540
Confidence Interval 95%
-1.789 to 0.708
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.635
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9034
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.077
Confidence Interval 95%
-1.327 to 1.173
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.636
Estimation Comments Tio R5 qd minus Placebo
13.Secondary Outcome
Title Mean Number of Puffs of Rescue Medication During the Whole Day (Last Week on Treatment, Response Values)
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing data for rescue medication.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 142 146 146 144
Mean (Standard Error)
Unit of Measure: Puffs
-0.569  (0.122) -0.802  (0.121) -0.783  (0.121) -0.769  (0.122)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0296
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.233
Confidence Interval 95%
-0.443 to -0.023
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.107
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0454
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.214
Confidence Interval 95%
-0.424 to -0.004
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.107
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0610
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.201
Confidence Interval 95%
-0.410 to 0.009
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.107
Estimation Comments Tio R5 qd minus Placebo
14.Secondary Outcome
Title Mean Number of Puffs of Rescue Medication During Daytime (Last Week on Treatment, Response Values)
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing data for rescue medication.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 142 146 146 144
Mean (Standard Error)
Unit of Measure: Puffs
-0.314  (0.071) -0.463  (0.071) -0.452  (0.071) -0.425  (0.071)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0183
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.149
Confidence Interval 95%
-0.273 to -0.025
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0288
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.138
Confidence Interval 95%
-0.262 to -0.014
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0781
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.111
Confidence Interval 95%
-0.235 to 0.013
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Tio R5 qd minus Placebo
15.Secondary Outcome
Title Mean Number of Puffs of Rescue Medication During Nighttime (Last Week on Treatment, Response Values)
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing data for rescue medication.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 142 146 146 144
Mean (Standard Error)
Unit of Measure: Puffs
-0.273  (0.064) -0.357  (0.063) -0.341  (0.063) -0.360  (0.064)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1303
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.084
Confidence Interval 95%
-0.193 to 0.025
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.055
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2191
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.068
Confidence Interval 95%
-0.177 to 0.041
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.055
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1163
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.087
Confidence Interval 95%
-0.196 to 0.022
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.056
Estimation Comments Tio R5 qd minus Placebo
16.Secondary Outcome
Title Mean Number of Night Awakenings During the Last Week on Treatment (Score, Response Values)
Hide Description MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS reduced to patients with non-missing data for nighttime awakenings
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 142 146 146 144
Mean (Standard Error)
Unit of Measure: Night awakenings
-0.156  (0.034) -0.166  (0.034) -0.162  (0.034) -0.187  (0.034)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7501
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.010
Confidence Interval 95%
-0.073 to 0.052
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.032
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8401
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.006
Confidence Interval 95%
-0.069 to 0.056
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.032
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3237
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.031
Confidence Interval 95%
-0.094 to 0.031
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.032
Estimation Comments Tio R5 qd minus Placebo
17.Secondary Outcome
Title FEV1 Area Under the Curve Within 24 Hours (h) Response (FEV1 AUC0-12h, FEV1 AUC12-24h, FEV1 AUC0-24h)
Hide Description MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC0-12, FEV1 AUC12-24 and FEV1 AUC0-24 were calculated using the trapezoidal rule divided by the observation time (12h resp. 24h) to report in litres.
Time Frame 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h, 4h, 11h 50min, 12h 30min, 13h, 14h, 15h, 16h, 18h, 20h, 22h, 23h, 23h 50min after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
FAS24 was defined as all patients in the FAS who gave informed consent for the 24-h PFT and who participated in this optional PFT.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 21 24 24 24
Mean (Standard Error)
Unit of Measure: Litres
FEV1 AUC0-12h -0.013  (0.058) 0.105  (0.055) 0.134  (0.054) 0.128  (0.054)
FEV1 AUC12-24h 0.012  (0.061) 0.093  (0.058) 0.148  (0.058) 0.208  (0.057)
FEV1 AUC0-24h -0.001  (0.057) 0.099  (0.054) 0.141  (0.054) 0.168  (0.053)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments Comparison vs. Placebo for AUC0-12h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1402
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.118
Confidence Interval (2-Sided) 95%
-0.040 to 0.276
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.079
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments Comparison vs. Placebo for AUC0-12h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0656
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.148
Confidence Interval (2-Sided) 95%
-0.010 to 0.305
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.079
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments Comparison vs. Placebo for AUC0-12h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0766
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.142
Confidence Interval (2-Sided) 95%
-0.015 to 0.299
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.079
Estimation Comments Tio R5 qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments Comparison vs. Placebo for AUC12-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3371
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.081
Confidence Interval (2-Sided) 95%
-0.086 to 0.249
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.084
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments Comparison vs. Placebo for AUC12-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1097
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.136
Confidence Interval (2-Sided) 95%
-0.031 to 0.303
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.084
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments Comparison vs. Placebo for AUC12-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0220
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.196
Confidence Interval (2-Sided) 95%
0.029 to 0.363
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.084
Estimation Comments Tio R5 qd minus Placebo
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments Comparison vs. Placebo for AUC0-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2062
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.100
Confidence Interval (2-Sided) 95%
-0.056 to 0.256
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.078
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments Comparison vs. Placebo for AUC0-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0731
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.142
Confidence Interval (2-Sided) 95%
-0.014 to 0.297
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.078
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments Comparison vs. Placebo for AUC0-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0333
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.169
Confidence Interval (2-Sided) 95%
0.014 to 0.324
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.078
Estimation Comments Tio R5 qd minus Placebo
18.Secondary Outcome
Title FVC Area Under the Curve Within 24 Hours (h) Response (FVC AUC0-12h, FVC AUC12-24h, FVC AUC0-24h)
Hide Description MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. FVC AUC0-12, FVC AUC12-24 and FVC AUC0-24 were calculated using the trapezoidal rule divided by the observation time (12h resp. 24h) to report in litres.
Time Frame 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h, 4h, 11h 50min, 12h 30min, 13h, 14h, 15h, 16h, 18h, 20h, 22h, 23h, 23h 50min after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
FAS24 was defined as all patients in the FAS who gave informed consent for the 24-h PFT and who participated in this optional PFT.
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description:
Matching Placebo qd in the evening delivered by the Respimat inhaler.
Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
Overall Number of Participants Analyzed 21 24 24 24
Mean (Standard Error)
Unit of Measure: Litres
FVC AUC0-12h -0.052  (0.072) 0.064  (0.068) 0.157  (0.068) 0.115  (0.068)
FVC AUC12-24h -0.021  (0.076) 0.046  (0.071) 0.177  (0.071) 0.160  (0.071)
FVC AUC0-24h -0.036  (0.072) 0.055  (0.067) 0.167  (0.067) 0.137  (0.067)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments Comparison vs. Placebo for AUC0-12h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2451
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.116
Confidence Interval (2-Sided) 95%
-0.081 to 0.312
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.099
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments Comparison vs. Placebo for AUC0-12h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0379
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.209
Confidence Interval (2-Sided) 95%
0.012 to 0.405
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.099
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments Comparison vs. Placebo for AUC0-12h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0957
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.167
Confidence Interval (2-Sided) 95%
-0.030 to 0.363
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.099
Estimation Comments Tio R5 qd minus Placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments Comparison vs. Placebo for AUC12-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5207
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.067
Confidence Interval (2-Sided) 95%
-0.139 to 0.273
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.104
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments Comparison vs. Placebo for AUC12-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0606
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.198
Confidence Interval (2-Sided) 95%
-0.009 to 0.404
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.104
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments Comparison vs. Placebo for AUC12-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0855
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.181
Confidence Interval (2-Sided) 95%
-0.026 to 0.387
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.104
Estimation Comments Tio R5 qd minus Placebo
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25 qd
Comments Comparison vs. Placebo for AUC0-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3564
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.091
Confidence Interval (2-Sided) 95%
-0.104 to 0.287
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.099
Estimation Comments Tio R1.25 qd minus Placebo
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5 qd
Comments Comparison vs. Placebo for AUC0-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0424
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.203
Confidence Interval (2-Sided) 95%
0.007 to 0.399
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.099
Estimation Comments Tio R2.5 qd minus Placebo
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5 qd
Comments Comparison vs. Placebo for AUC0-24h
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0815
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM, adjusted for treatment, period, patient and study baseline.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.174
Confidence Interval (2-Sided) 95%
-0.022 to 0.370
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.099
Estimation Comments Tio R5 qd minus Placebo
Time Frame 4 weeks + 30 days if in last period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Hide Arm/Group Description Matching Placebo qd in the evening delivered by the Respimat inhaler. Tiotropium 1.25 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS. Tiotropium 2.5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS. Tiotropium 5 mcg qd in the evening delivered by the Respimat inhaler as add-on therapy to ICS.
All-Cause Mortality
Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/144 (0.00%)   0/146 (0.00%)   0/147 (0.00%)   2/146 (1.37%) 
Gastrointestinal disorders         
Inguinal hernia  1  0/144 (0.00%)  0/146 (0.00%)  0/147 (0.00%)  1/146 (0.68%) 
Psychiatric disorders         
Alcohol abuse  1  0/144 (0.00%)  0/146 (0.00%)  0/147 (0.00%)  1/146 (0.68%) 
Panic attack  1  0/144 (0.00%)  0/146 (0.00%)  0/147 (0.00%)  1/146 (0.68%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Tio R1.25 qd Tio R2.5 qd Tio R5 qd
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/144 (0.00%)   0/146 (0.00%)   0/147 (0.00%)   0/146 (0.00%) 
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 of the results of this trial are described in the investigator contract.
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01233284     History of Changes
Other Study ID Numbers: 205.380
2010-018471-26 ( EudraCT Number: EudraCT )
First Submitted: November 2, 2010
First Posted: November 3, 2010
Results First Submitted: December 14, 2012
Results First Posted: January 21, 2013
Last Update Posted: December 24, 2013