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Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Moderate Persistent Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01257230
Recruitment Status : Completed
First Posted : December 9, 2010
Results First Posted : August 8, 2014
Last Update Posted : September 5, 2014
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: tiotropium Respimat low dose
Drug: placebo Respimat
Drug: tiotropium Respimat high dose
Enrollment 398
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler.
Period Title: Overall Study
Started 138 125 135
Completed 132 115 129
Not Completed 6 10 6
Reason Not Completed
Not Treated             0             0             1
Adverse Event             2             0             0
Lack of Efficacy             0             1             0
Protocol Violation             3             0             1
Withdrawal by Subject             0             4             1
Other reason not defined above             1             5             3
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5 Total
Hide Arm/Group Description Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler Total of all reporting groups
Overall Number of Baseline Participants 138 125 134 397
Hide Baseline Analysis Population Description
Treated set which included all randomised patients who were dispensed trial medication and received at least one documented dose of trial medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 138 participants 125 participants 134 participants 397 participants
14.2  (1.7) 14.2  (1.8) 14.5  (1.6) 14.3  (1.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 138 participants 125 participants 134 participants 397 participants
Female
50
  36.2%
44
  35.2%
45
  33.6%
139
  35.0%
Male
88
  63.8%
81
  64.8%
89
  66.4%
258
  65.0%
1.Primary Outcome
Title FEV1 peak0-3 Change From Baseline
Hide Description

Change from baseline in peak Forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak0-3) measured at week 24.

Note, the measured values presented are actually adjusted means.

Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) was the same as the treated set which included all randomised patients who were dispensed trial medication and received at least one documents dose of trial medication. Missing data at a visit was imputed by the available data from the patient at that visit, completely missing visits were handled by the statistical model.
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 137 120 131
Mean (Standard Error)
Unit of Measure: Litres
0.373  (0.037) 0.507  (0.040) 0.547  (0.038)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0085
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.134
Confidence Interval (2-Sided) 95%
0.034 to 0.234
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.051
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.174
Confidence Interval (2-Sided) 95%
0.076 to 0.272
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.050
Estimation Comments Difference calculated as Tio R5 minus placebo
2.Secondary Outcome
Title Trough FEV1 Change From Baseline
Hide Description

Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 24.

The measured values presented are actually adjusted means.

Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Missing data at a visit was imputed by the available data from the patient at that visit, completely missing visits were handled by the statistical model.
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 137 119 131
Mean (Standard Error)
Unit of Measure: Litres
0.283  (0.040) 0.367  (0.044) 0.400  (0.041)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1307
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.084
Confidence Interval (2-Sided) 95%
-0.025 to 0.194
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.056
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0320
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.117
Confidence Interval (2-Sided) 95%
0.010 to 0.223
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.054
Estimation Comments Difference calculated as Tio R5 minus placebo
3.Secondary Outcome
Title FVC peak0-3 Change From Baseline
Hide Description

Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 h after administration of trial medication (FVC peak0-3h) after 24 weeks of treatment.

The measured values presented are actually adjusted means.

Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Missing data at a visit was imputed by the available data from the patient at that visit, completely missing visits were handled by the statistical model.
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 137 120 131
Mean (Standard Error)
Unit of Measure: Litres
0.331  (0.041) 0.419  (0.045) 0.403  (0.043)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1231
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.088
Confidence Interval (2-Sided) 95%
-0.024 to 0.200
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.057
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1950
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.072
Confidence Interval (2-Sided) 95%
-0.037 to 0.182
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.056
Estimation Comments Difference calculated as Tio R5 minus placebo
4.Secondary Outcome
Title Trough FVC Change From Baseline
Hide Description

Change from baseline of Trough (pre-dose) forced vital capacity (FVC) measured 10 min before the administration of trial medication after 24 weeks of treatment.

The measured values presented are actually adjusted means..

Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Missing data at a visit was imputed by the available data from the patient at that visit, completely missing visits were handled by the statistical model.
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 137 119 131
Mean (Standard Error)
Unit of Measure: Litres
0.281  (0.043) 0.345  (0.047) 0.316  (0.045)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2921
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.063
Confidence Interval (2-Sided) 95%
-0.055 to 0.181
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.060
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5495
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.035
Confidence Interval (2-Sided) 95%
-0.080 to 0.150
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.059
Estimation Comments Difference calculated as Tio R5 minus placebo
5.Secondary Outcome
Title FEV1 AUC (0-3h) Change From Baseline
Hide Description

Change from baseline of area under the curve (AUC) from 0 to 3 h for FEV1 (FEV1 AUC 0-3h) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).

The measured values presented are actually adjusted means.

Time Frame Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Missing data at a visit was imputed by the available data from the patient at that visit, completely missing visits were handled by the statistical model.
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 137 119 131
Mean (Standard Error)
Unit of Measure: Litres
0.281  (0.035) 0.411  (0.038) 0.463  (0.036)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0079
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.130
Confidence Interval (2-Sided) 95%
0.034 to 0.225
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.049
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.181
Confidence Interval (2-Sided) 95%
0.088 to 0.275
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.048
Estimation Comments Difference calculated as Tio R5 minus placebo
6.Secondary Outcome
Title FVC AUC (0-3h) Change From Baseline
Hide Description

Change from baseline of area under the curve (AUC) from 0 to 3 h for FVC (FVC AUC0-3h) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).

The measured values presented are actually adjusted means.

Time Frame Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Missing data at a visit was imputed by the available data from the patient at that visit, completely missing visits were handled by the statistical model.
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 137 119 131
Mean (Standard Error)
Unit of Measure: Litres
0.240  (0.039) 0.330  (0.042) 0.311  (0.040)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0945
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.090
Confidence Interval (2-Sided) 95%
-0.016 to 0.196
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.054
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1755
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.071
Confidence Interval (2-Sided) 95%
-0.032 to 0.175
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.053
Estimation Comments Difference calculated as Tio R5 minus placebo
7.Secondary Outcome
Title FEF25-75 Change From Baseline
Hide Description

Change from baseline in mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75%), also known as maximum mid-expiratory flow, at individual time points after 24 weeks of treatment.

The measured values presented are actually adjusted means.

Time Frame Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Missing data at a visit was imputed by the available data from the patient at that visit, completely missing visits were handled by the statistical model.
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 137 120 131
Mean (Standard Error)
Unit of Measure: Litres per second
10 minutes pre-dose (n=137, 119, 131) 0.332  (0.072) 0.461  (0.079) 0.609  (0.074)
30 minutes post-dose 0.372  (0.066) 0.536  (0.072) 0.763  (0.068)
1 hour post-dose 0.359  (0.067) 0.596  (0.072) 0.835  (0.069)
2 hours post-dose 0.403  (0.069) 0.615  (0.075) 0.857  (0.071)
3 hours post-dose 0.347  (0.068) 0.653  (0.074) 0.850  (0.070)
8.Secondary Outcome
Title Use of PRN Rescue Medication During the Daytime
Hide Description

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the daytime based on the weekly mean at week 24.

The measured values presented are actually adjusted means.

Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 132 114 122
Mean (Standard Error)
Unit of Measure: Number of puffs of rescue medication
-0.206  (0.066) -0.209  (0.071) -0.215  (0.068)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9760
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.003
Confidence Interval (2-Sided) 95%
-0.184 to 0.178
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.092
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9224
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.009
Confidence Interval (2-Sided) 95%
-0.186 to 0.168
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.090
Estimation Comments Difference calculated as Tio R5 minus placebo
9.Secondary Outcome
Title Use of PRN Rescue Medication During the Night-time
Hide Description

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the night-time based on the weekly mean at week 24.

The measured values presented are actually adjusted means.

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 132 110 124
Mean (Standard Error)
Unit of Measure: Number of puffs of rescue medication
-0.144  (0.059) -0.122  (0.064) -0.032  (0.061)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7852
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.023
Confidence Interval (2-Sided) 95%
-0.140 to 0.185
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.083
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1649
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.112
Confidence Interval (2-Sided) 95%
-0.046 to 0.271
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.081
Estimation Comments Difference calculated as Tio R5 minus placebo
10.Secondary Outcome
Title Use of PRN Rescue Medication During the Day
Hide Description

Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the day (24 hour period) based on the weekly mean at week 24.

The measured values presented are actually adjusted means.

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 135 117 125
Mean (Standard Error)
Unit of Measure: Number of puffs of rescue medication
-0.524  (0.098) -0.556  (0.104) -0.480  (0.100)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8253
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.032
Confidence Interval (2-Sided) 95%
-0.312 to 0.249
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.143
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7559
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.044
Confidence Interval (2-Sided) 95%
-0.232 to 0.319
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.140
Estimation Comments Difference calculated as Tio R5 minus placebo
11.Secondary Outcome
Title Control of Asthma as Assessed by ACQ Total Score
Hide Description

Change from baseline in Asthma Control Questionnaire (ACQ) total score measured at week 24.

The ACQ is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment. ACQ total score was calculated as the mean of the responses to all 7 questions.

The measured values presented are actually adjusted means.

Time Frame Baseline and week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 136 120 132
Mean (Standard Error)
Unit of Measure: Units on a scale
1.213  (0.062) 1.053  (0.067) 1.116  (0.064)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0653
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.160
Confidence Interval (2-Sided) 95%
-0.330 to 0.010
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.087
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2516
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.097
Confidence Interval (2-Sided) 95%
-0.263 to 0.069
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.084
Estimation Comments Difference calculated as Tio R5 minus placebo
12.Secondary Outcome
Title ACQ Total Score Responders
Hide Description

Responder rates based on the ACQ total score after 24 weeks of treatment. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≤-0.5), no change (-0.5 <change from trial baseline <0.5) and worsening (change from trial baseline ≥0.5)

The ACQ is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment.

Time Frame Week 24
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FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
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Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 138 125 134
Measure Type: Number
Unit of Measure: percentage of participants
Responder 66.7 76.0 74.6
No change 27.5 21.6 23.1
Worsening 5.8 2.4 2.2
13.Secondary Outcome
Title Control of Asthma as Assessed by ACQ6
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Change from baseline in AQC6 score at week 24.

The ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ. The ACQ is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment.

The measured values presented are actually adjusted means.

Time Frame Baseline and week 24
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FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 136 120 132
Mean (Standard Error)
Unit of Measure: units on a scale
1.173  (0.068) 1.026  (0.073) 1.119  (0.070)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1200
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.147
Confidence Interval (2-Sided) 95%
-0.333 to 0.038
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.095
Estimation Comments Difference calculated as Tio R2.5 minus placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5589
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.054
Confidence Interval (2-Sided) 95%
-0.235 to 0.127
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.092
Estimation Comments Difference calculated as Tio R5 minus placebo
14.Secondary Outcome
Title ACQ6 Responders
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Responder rates based on the ACQ6 after 24 weeks of treatment. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≤-0.5), no change (-0.5 <change from trial baseline <0.5) and worsening (change from trial baseline ≥0.5)

The ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ. The ACQ is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment.

Time Frame Week 24
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Hide Analysis Population Description
FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 138 125 134
Measure Type: Number
Unit of Measure: percentage of participants
Responder 69.6 76.8 72.4
No change 22.5 20.0 23.1
Worsening 8.0 3.2 4.5
15.Secondary Outcome
Title Time to First Severe Asthma Exacerbation During the 48 Week Treatment Period
Hide Description The median time to first severe asthma exacerbation was not calculable, so the number of patients who experienced a severe asthma exacerbation are presented for the measured values. A severe asthma exacerbation was defined as a subgroup of all asthma exacerbations that required treatment with systemic corticosteroid for at least 3 days.
Time Frame 48 weeks
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FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 138 125 134
Measure Type: Number
Unit of Measure: Participants
9 5 2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4023
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.21 to 1.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0620
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.05 to 1.08
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Time to First Asthma Exacerbation During the 48 Week Treatment Period
Hide Description The median time to first asthma exacerbation was not calculable, so the number of patients who experienced an asthma exacerbation are presented for the measured values.
Time Frame Week 48
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FAS
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description:
Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
Overall Number of Participants Analyzed 138 125 134
Measure Type: Number
Unit of Measure: Participants
37 34 30
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R2.5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8700
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.65 to 1.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Respimat, Tio R5
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4198
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.51 to 1.33
Estimation Comments [Not Specified]
Time Frame From first drug administration until 30 days after last drug intake, up to 416 days
Adverse Event Reporting Description Treated set which included all randomised patients who were dispensed trial medication and received at least one documented dose of trial medication.
 
Arm/Group Title Placebo Respimat Tio R2.5 Tio R5
Hide Arm/Group Description Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler
All-Cause Mortality
Placebo Respimat Tio R2.5 Tio R5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo Respimat Tio R2.5 Tio R5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/138 (1.45%)   2/125 (1.60%)   3/134 (2.24%) 
Gastrointestinal disorders       
Abdominal pain upper  1  0/138 (0.00%)  0/125 (0.00%)  1/134 (0.75%) 
Gastrointestinal disorder  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Peritoneal haemorrhage  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Retroperitoneal haematoma  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Hepatobiliary disorders       
Liver injury  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Immune system disorders       
Allergy to plants  1  0/138 (0.00%)  0/125 (0.00%)  1/134 (0.75%) 
Anaphylactic reaction  1  0/138 (0.00%)  0/125 (0.00%)  1/134 (0.75%) 
Infections and infestations       
Appendicitis  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Gastroenteritis  1  1/138 (0.72%)  0/125 (0.00%)  0/134 (0.00%) 
Injury, poisoning and procedural complications       
Arterial injury  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Hepatic rupture  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Multiple injuries  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Wound  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Musculoskeletal and connective tissue disorders       
Compartment syndrome  1  0/138 (0.00%)  1/125 (0.80%)  0/134 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Teratoma  1  1/138 (0.72%)  0/125 (0.00%)  0/134 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  0/138 (0.00%)  0/125 (0.00%)  1/134 (0.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Respimat Tio R2.5 Tio R5
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   62/138 (44.93%)   55/125 (44.00%)   61/134 (45.52%) 
Infections and infestations       
Nasopharyngitis  1  17/138 (12.32%)  13/125 (10.40%)  20/134 (14.93%) 
Respiratory tract infection viral  1  11/138 (7.97%)  11/125 (8.80%)  10/134 (7.46%) 
Tonsillitis  1  7/138 (5.07%)  2/125 (1.60%)  1/134 (0.75%) 
Upper respiratory tract infection  1  6/138 (4.35%)  2/125 (1.60%)  7/134 (5.22%) 
Viral infection  1  6/138 (4.35%)  5/125 (4.00%)  7/134 (5.22%) 
Investigations       
Peak expiratory flow rate decreased  1  8/138 (5.80%)  9/125 (7.20%)  6/134 (4.48%) 
Nervous system disorders       
Headache  1  2/138 (1.45%)  7/125 (5.60%)  9/134 (6.72%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  32/138 (23.19%)  27/125 (21.60%)  22/134 (16.42%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 16.1
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.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights.
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: NCT01257230    
Other Study ID Numbers: 205.444
2010-021093-11 ( EudraCT Number: EudraCT )
First Submitted: December 6, 2010
First Posted: December 9, 2010
Results First Submitted: June 12, 2014
Results First Posted: August 8, 2014
Last Update Posted: September 5, 2014