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Efficacy and Safety of 3 Doses of Tiotropium Compared to Placebo in Adolescents (12 to 17 Yrs) With Moderate Asthma

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ClinicalTrials.gov Identifier: NCT01122680
Recruitment Status : Completed
First Posted : May 13, 2010
Results First Posted : June 27, 2012
Last Update Posted : May 16, 2014
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
Drug: tiotropium bromide
Drug: Placebo
Enrollment 105
Recruitment Details In this incomplete crossover design, 105 patients were randomised to one of four sequences (in general terms, ABC, BDA, CAD or DCB). Whilst there were 4 possible treatments, A, B, C and D, each patient would receive a maximum of 3 different treatments. Hence, approximately 75 patients would receive each of A, B, C and D at any timepoint.
Pre-assignment Details  
Arm/Group Title Tio R5/Placebo/Tio R1.25 Tio R1.25/Tio R5/Tio R2.5 Placebo/Tio R2.5/Tio R5 Tio R2.5/Tio R1.25/Placebo
Hide Arm/Group Description Patients treated with Tiotropium 5 mcg in Phase I, with a matching Placebo in Phase II and with Tiotropium 1.25 mcg in Phase III. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off-treatment periods) between treatments. Patients treated with Tiotropium 1.25 mcg in Phase I, with Tiotropium 5 mcg in Phase II and with Tiotropium 2.5 mcg in Phase III. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off-treatment periods) between treatments. Patients treated with a matching Placebo in Phase I, with Tiotropium 2.5 mcg in Phase II and with Tiotropium 5 mcg in Phase III. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off-treatment periods) between treatments. Patients treated with Tiotropium 2.5 mcg in Phase I, with Tiotropium 1.25 mcg in Phase II and with a matching Placebo in Phase III. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off-treatment periods) between treatments.
Period Title: Period 1 (4 Weeks)
Started 29 [1] 26 [1] 26 [1] 24 [1]
Completed 26 [2] 25 [2] 26 [2] 24 [2]
Not Completed 3 1 0 0
Reason Not Completed
Adverse Event             1             0             0             0
Protocol Violation             1             0             0             0
Other             1             1             0             0
[1]
Entered this study period.
[2]
Completed treatment in this crossover period.
Period Title: Period 2 (4 Weeks)
Started 26 [1] 25 [1] 26 [1] 24 [1]
Completed 25 [2] 25 [2] 26 [2] 23 [2]
Not Completed 1 0 0 1
Reason Not Completed
Protocol Violation             0             0             0             1
Other             1             0             0             0
[1]
Entered this study period.
[2]
Completed treatment in this crossover period.
Period Title: Period 3 (4 Weeks)
Started 25 [1] 25 [1] 26 [1] 23 [1]
Completed 24 [2] 24 [2] 26 [2] 23 [2]
Not Completed 1 1 0 0
Reason Not Completed
Adverse Event             1             0             0             0
Withdrawal by Subject             0             1             0             0
[1]
Entered this study period.
[2]
Completed treatment in this crossover period.
Arm/Group Title Total.
Hide Arm/Group Description Total number of patients randomised and treated at all in the study.
Overall Number of Baseline Participants 105
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 105 participants
14.0  (1.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants
Female
38
  36.2%
Male
67
  63.8%
Forced expiratory volume in 1s (FEV1)  
Mean (Standard Deviation)
Unit of measure:  Litre
Number Analyzed 105 participants
2.742  (0.697)
1.Primary Outcome
Title Forced Expiratory Volume (FEV1) Peak (0-3h) Response
Hide Description The FEV1 peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FEV1 measured within the first 3 hours post dosing and the FEV1 baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full analysis set (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. This patient set is therefore FAS reduced to patients with non-missing FEV1 data.
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Litre
0.489  (0.047) 0.556  (0.047) 0.546  (0.047) 0.602  (0.046)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R5
Comments Tio R5 minus Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0043
Comments First step of closed testing procedure, where the active treatments are compared to placebo. If this statisical test significant at the 0.05 alpha level then proceed to comparison of the next lower dose to placebo.
Method Mixed model repeated measures (MMRM)
Comments This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.113
Confidence Interval 95%
0.036 to 0.190
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.039
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R2.5
Comments Tio R2.5 minus Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1484
Comments Second step of closed testing procedure. If this statisical test significant at the 0.05 alpha level then proceed to comparison of the next lower dose to placebo.
Method Mixed effect repeated measures (MMRM)
Comments This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.057
Confidence Interval 95%
-0.021 to 0.135
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.039
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Tio R1.25
Comments Tio R1.25 minus Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0664
Comments This test is considered as descriptive.
Method Mixed effect repeated measures (MMRM)
Comments This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.067
Confidence Interval 95%
-0.005 to 0.138
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tio R1.25, Tio R5
Comments Tio R5 minus Tio R1.25
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect repeated measures (MMRM)
Comments This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.046
Confidence Interval 95%
-0.031 to 0.124
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.039
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Tio R2.5, Tio R5
Comments Tio R5 minus Tio R2.5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect repeated measures (MMRM)
Comments This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.056
Confidence Interval 95%
-0.014 to 0.126
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.036
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Tio R1.25, Tio R2.5
Comments Tio R2.5 minus Tio R1.25
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect repeated measures (MMRM)
Comments This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.010
Confidence Interval 95%
-0.088 to 0.069
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.040
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Trough FEV1 Response
Hide Description The trough FEV1 is defined as the pre-dose FEV1 measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing FEV1 data.
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Litre
0.292  (0.045) 0.384  (0.045) 0.353  (0.045) 0.442  (0.045)
3.Secondary Outcome
Title FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response
Hide Description FEV1 (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing FEV1 data.
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Litre
0.363  (0.045) 0.455  (0.045) 0.434  (0.045) 0.497  (0.045)
4.Secondary Outcome
Title FEV1 Individual Measurements Response at Each Time-point
Hide Description Individual FEV1 measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing FEV1 data.
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Litre
Timepoint -0:10 hr response 0.292  (0.045) 0.384  (0.045) 0.353  (0.045) 0.442  (0.045)
Timepoint 0:30 hr response 0.337  (0.047) 0.456  (0.047) 0.407  (0.047) 0.486  (0.047)
Timepoint 1:00 hr response 0.353  (0.048) 0.456  (0.048) 0.416  (0.048) 0.505  (0.047)
Timepoint 2:00 hr response 0.394  (0.047) 0.467  (0.048) 0.453  (0.047) 0.501  (0.047)
Timepoint 3:00 hr response 0.396  (0.048) 0.467  (0.048) 0.489  (0.048) 0.497  (0.047)
5.Secondary Outcome
Title Forced Vital Capacity (FVC) Peak (0-3h) Response
Hide Description The FVC peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FVC measured within the first 3 hours post dosing and the FVC baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing FVC data.
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Litre
0.546  (0.049) 0.554  (0.049) 0.554  (0.048) 0.548  (0.048)
6.Secondary Outcome
Title FVC Trough Response
Hide Description The trough FVC response is defined as the pre-dose FVC measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing FVC data.
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Litre
0.357  (0.047) 0.375  (0.047) 0.381  (0.047) 0.400  (0.047)
7.Secondary Outcome
Title FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response
Hide Description FVC (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing FVC data.
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Litre
0.413  (0.046) 0.441  (0.046) 0.417  (0.045) 0.429  (0.045)
8.Secondary Outcome
Title FVC Individual Measurements at Each Time-point
Hide Description Individual FVC measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing FVC data.
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Litre
Timepoint -0:10 hr response 0.357  (0.047) 0.375  (0.047) 0.381  (0.047) 0.400  (0.047)
Timepoint 0:30 hr response 0.397  (0.049) 0.434  (0.049) 0.394  (0.049) 0.409  (0.049)
Timepoint 1:00 hr response 0.417  (0.049) 0.443  (0.050) 0.387  (0.049) 0.448  (0.049)
Timepoint 2:00 hr response 0.429  (0.048) 0.438  (0.048) 0.444  (0.048) 0.423  (0.048)
Timepoint 3:00 hr response 0.430  (0.048) 0.461  (0.048) 0.454  (0.048) 0.456  (0.048)
9.Secondary Outcome
Title Forced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point
Hide Description FEF 25-75% is the mean forced expiratory flow between 25% and 75% of the FVC determined at the end of the 4-week treatment period. This is often referred to as the maximum midexpiratory flow. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing FEF data
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 49 47 47 50
Least Squares Mean (Standard Error)
Unit of Measure: Litre
Timepoint -0:10 hr response 0.242  (0.081) 0.533  (0.082) 0.380  (0.082) 0.566  (0.080)
Timepoint 0:30 hr response 0.268  (0.083) 0.643  (0.084) 0.513  (0.084) 0.647  (0.082)
Timepoint 1:00 hr response 0.321  (0.087) 0.655  (0.087) 0.569  (0.087) 0.641  (0.086)
Timepoint 2:00 hr response 0.357  (0.088) 0.678  (0.089) 0.607  (0.089) 0.622  (0.087)
Timepoint 3:00 hr response 0.329  (0.083) 0.662  (0.084) 0.616  (0.084) 0.620  (0.083)
10.Secondary Outcome
Title Mean Morning Peak Expiratory Flow (PEF) Response
Hide Description Mean morning PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing morning PEF data
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 73 75 73 79
Least Squares Mean (Standard Error)
Unit of Measure: Litre/min
7.267  (6.152) 18.613  (6.118) 23.185  (6.146) 20.491  (6.031)
11.Secondary Outcome
Title Mean Evening PEF Response
Hide Description Mean evening PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing evening PEF data
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 73 74 75 79
Least Squares Mean (Standard Error)
Unit of Measure: Litre/min
-0.552  (6.098) 5.985  (6.089) 18.971  (6.043) 16.565  (5.970)
12.Secondary Outcome
Title Change From Baseline in the Number of Puffs of Rescue Medication Per Day
Hide Description Mean number of inhalations (puffs) of unscheduled rescue salbutamol therapy during whole day. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing data for rescue medication
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 73 73 73 79
Least Squares Mean (Standard Error)
Unit of Measure: Puffs/day
-0.412  (0.155) -0.635  (0.156) -0.521  (0.154) -0.528  (0.151)
13.Secondary Outcome
Title Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ)
Hide Description ACQ is a questionnaire consisting of a seven point Likert scale ranging from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The scale describes the frequency and severity of asthma symptoms. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing ACQ data
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 74 73 74 77
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
1.371  (0.078) 1.189  (0.079) 1.366  (0.078) 1.287  (0.078)
14.Secondary Outcome
Title Change From Baseline in Mean Number of Nighttime Awakenings
Hide Description Mean number of nighttime awakenings due to asthma symptoms as assessed by patients eDiary incorporated in the AM3® device. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time Frame Baseline and last week of treatment (week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS with non-missing data for nighttime awakenings
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description:
Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Overall Number of Participants Analyzed 73 75 73 79
Least Squares Mean (Standard Error)
Unit of Measure: Night awakenings per week
-0.086  (0.030) -0.027  (0.030) -0.074  (0.030) -0.066  (0.029)
Time Frame 4 weeks + 30 days if in last period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Tio R1.25 Tio R2.5 Tio R5
Hide Arm/Group Description Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
All-Cause Mortality
Placebo Tio R1.25 Tio R2.5 Tio R5
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 Tio R2.5 Tio R5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/75 (0.00%)   1/75 (1.33%)   0/75 (0.00%)   1/80 (1.25%) 
Infections and infestations         
H1N1 influenza  1  0/75 (0.00%)  1/75 (1.33%)  0/75 (0.00%)  0/80 (0.00%) 
Pneumonia mycoplasmal  1  0/75 (0.00%)  1/75 (1.33%)  0/75 (0.00%)  0/80 (0.00%) 
Nervous system disorders         
Presyncope  1  0/75 (0.00%)  0/75 (0.00%)  0/75 (0.00%)  1/80 (1.25%) 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/75 (0.00%)  1/75 (1.33%)  0/75 (0.00%)  0/80 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
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 Tio R2.5 Tio R5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/75 (0.00%)   0/75 (0.00%)   0/75 (0.00%)   0/80 (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
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
ClinicalTrials.gov Identifier: NCT01122680     History of Changes
Other Study ID Numbers: 205.424
2009-017745-55 ( EudraCT Number: EudraCT )
First Submitted: May 11, 2010
First Posted: May 13, 2010
Results First Submitted: April 10, 2012
Results First Posted: June 27, 2012
Last Update Posted: May 16, 2014