Trial Outcomes & Findings for Safety and Efficacy of 12-wk Treatment With Two Doses of Tiotropium Respimat in Cystic Fibrosis (NCT NCT00737100)
NCT ID: NCT00737100
Last Updated: 2014-05-16
Results Overview
Outcome measure description: Change from baseline in percent predicted Forced Expiratory Volume in one second (FEV1) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
510 participants
Primary outcome timeframe
Baseline, Week 12
Results posted on
2014-05-16
Participant Flow
Participant milestones
| Measure |
Placebo
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
168
|
166
|
176
|
|
Overall Study
COMPLETED
|
161
|
159
|
169
|
|
Overall Study
NOT COMPLETED
|
7
|
7
|
7
|
Reasons for withdrawal
| Measure |
Placebo
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
6
|
5
|
3
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
3
|
|
Overall Study
Reason discontinued not explained above
|
1
|
1
|
1
|
Baseline Characteristics
Safety and Efficacy of 12-wk Treatment With Two Doses of Tiotropium Respimat in Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Placebo
n=168 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=166 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=176 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
Total
n=510 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
20.4 years
STANDARD_DEVIATION 11.6 • n=99 Participants
|
21.5 years
STANDARD_DEVIATION 12.0 • n=107 Participants
|
20.7 years
STANDARD_DEVIATION 11.3 • n=206 Participants
|
20.9 years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
|
Age, Customized
<= 11 years
|
44 years
n=99 Participants
|
42 years
n=107 Participants
|
52 years
n=206 Participants
|
138 years
n=7 Participants
|
|
Age, Customized
>= 12 years
|
124 years
n=99 Participants
|
124 years
n=107 Participants
|
124 years
n=206 Participants
|
372 years
n=7 Participants
|
|
Sex: Female, Male
Female
|
72 Participants
n=99 Participants
|
81 Participants
n=107 Participants
|
82 Participants
n=206 Participants
|
235 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
96 Participants
n=99 Participants
|
85 Participants
n=107 Participants
|
94 Participants
n=206 Participants
|
275 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
2 participants
n=206 Participants
|
3 participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
0 participants
n=99 Participants
|
3 participants
n=107 Participants
|
2 participants
n=206 Participants
|
5 participants
n=7 Participants
|
|
Race/Ethnicity, Customized
White
|
127 participants
n=99 Participants
|
124 participants
n=107 Participants
|
132 participants
n=206 Participants
|
383 participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Missing
|
39 participants
n=99 Participants
|
35 participants
n=107 Participants
|
37 participants
n=206 Participants
|
111 participants
n=7 Participants
|
|
Race/Ethnicity, Customized
American Indian / Alaskan native
|
2 participants
n=99 Participants
|
3 participants
n=107 Participants
|
3 participants
n=206 Participants
|
8 participants
n=7 Participants
|
|
Height
|
157.4 centimeters
STANDARD_DEVIATION 17.2 • n=99 Participants
|
157.7 centimeters
STANDARD_DEVIATION 17.0 • n=107 Participants
|
155.7 centimeters
STANDARD_DEVIATION 18.2 • n=206 Participants
|
156.9 centimeters
STANDARD_DEVIATION 17.5 • n=7 Participants
|
|
Weight
|
52.1 kilograms
STANDARD_DEVIATION 19.0 • n=99 Participants
|
51.0 kilograms
STANDARD_DEVIATION 17.3 • n=107 Participants
|
50.4 kilograms
STANDARD_DEVIATION 18.2 • n=206 Participants
|
51.2 kilograms
STANDARD_DEVIATION 18.1 • n=7 Participants
|
|
Body Mass Index
|
20.3 kilogram/square meter
STANDARD_DEVIATION 4.4 • n=99 Participants
|
19.9 kilogram/square meter
STANDARD_DEVIATION 4.0 • n=107 Participants
|
20.0 kilogram/square meter
STANDARD_DEVIATION 4.1 • n=206 Participants
|
20.1 kilogram/square meter
STANDARD_DEVIATION 4.2 • n=7 Participants
|
|
Alcohol history
Drinks no alcohol
|
130 Participants
n=99 Participants
|
112 Participants
n=107 Participants
|
132 Participants
n=206 Participants
|
374 Participants
n=7 Participants
|
|
Alcohol history
Drinks alcohol but should not interfere with trial
|
38 Participants
n=99 Participants
|
54 Participants
n=107 Participants
|
43 Participants
n=206 Participants
|
135 Participants
n=7 Participants
|
|
Alcohol history
Drinks alcohol but could interfere with trial
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Smoking history
Never smoked
|
159 Participants
n=99 Participants
|
157 Participants
n=107 Participants
|
167 Participants
n=206 Participants
|
483 Participants
n=7 Participants
|
|
Smoking history
Ex-smoker
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
19 Participants
n=7 Participants
|
|
Smoking history
Currently smokes
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
Outcome measure description: Change from baseline in percent predicted Forced Expiratory Volume in one second (FEV1) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.
Outcome measures
| Measure |
Placebo
n=163 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=158 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=169 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Percent Predicted FEV1 AUC0-4 Response at the End of Week 12
|
-1.74 Percentage change
Standard Error 0.65
|
1.20 Percentage change
Standard Error 0.66
|
1.65 Percentage change
Standard Error 0.63
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
Outcome measure description: Change from baseline in percent predicted trough Forced Expiratory Volume in one second. Calculated as percent predicted at week 12 minus percent predicted at baseline.
Outcome measures
| Measure |
Placebo
n=163 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=158 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=169 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Percent Predicted FEV1 Trough Response at the End of Week 12
|
-1.44 Percentage change
Standard Error 0.71
|
0.81 Percentage change
Standard Error 0.71
|
0.78 Percentage change
Standard Error 0.69
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
Change from baseline in percent predicted Forced Vital Capacity (FVC) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.
Outcome measures
| Measure |
Placebo
n=149 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=150 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=158 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Percent Predicted FVC AUC0-4 Response at the End of Week 12
|
-1.30 Percentage change
Standard Error 0.74
|
0.53 Percentage change
Standard Error 0.74
|
1.81 Percentage change
Standard Error 0.72
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
Change from baseline in percent predicted trough Forced Vital Capacity (FVC). Calculated as percent predicted at week 12 minus percent predicted at baseline.
Outcome measures
| Measure |
Placebo
n=149 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=150 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=158 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Percent Predicted FVC Trough Response at the End of Week 12
|
-0.39 Percentage change
Standard Error 0.73
|
0.47 Percentage change
Standard Error 0.72
|
0.81 Percentage change
Standard Error 0.70
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
Forced Expiratory Flow at 25-75% of vital capacity (FEF25-75). Calculated as percent predicted at week 12 minus percent predicted at baseline.
Outcome measures
| Measure |
Placebo
n=150 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=152 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=158 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Pre-bronchodilator FEF25-75 Percent Predicted at the End of Week 12
|
-1.40 Percentage change
Standard Error 1.57
|
2.78 Percentage change
Standard Error 1.55
|
3.94 Percentage change
Standard Error 1.52
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
Change from baseline in static lung hyperinflation as measured by RV/TLC. Calculated as percent predicted at week 12 minus percent predicted at baseline.
Outcome measures
| Measure |
Placebo
n=53 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=54 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=54 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Change From Baseline in Residual Volume/Total Lung Capacity (RV/TLC) at the End of Week 12
|
-0.01 Percentage change
Standard Error 0.03
|
0.00 Percentage change
Standard Error 0.03
|
0.04 Percentage change
Standard Error 0.03
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
Outcome measure description: The RSSQ questionnaire is used to determine the presence or absence of an exacerbation during the recall period.
Outcome measures
| Measure |
Placebo
n=167 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=166 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=175 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Respiratory and Systemic Symptoms Questionnaire (RSSQ)
At least one pulmonary exacerbation
|
16 Participants
|
13 Participants
|
12 Participants
|
|
Respiratory and Systemic Symptoms Questionnaire (RSSQ)
No pulmonary exacerbation
|
151 Participants
|
153 Participants
|
163 Participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adults with CF. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.
Outcome measures
| Measure |
Placebo
n=168 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=166 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=176 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Change From Baseline in CFQ Scores - Adult Group
Physical (N=99, 102, 105)
|
-2.5 units on a scale
Standard Deviation 14.8
|
-0.0 units on a scale
Standard Deviation 14.1
|
-2.9 units on a scale
Standard Deviation 11.4
|
|
Change From Baseline in CFQ Scores - Adult Group
Role (N=94, 100, 103)
|
0.7 units on a scale
Standard Deviation 12.0
|
-2.7 units on a scale
Standard Deviation 12.0
|
-2.1 units on a scale
Standard Deviation 15.1
|
|
Change From Baseline in CFQ Scores - Adult Group
Vitality (N=99, 101, 105)
|
-2.3 units on a scale
Standard Deviation 15.0
|
-1.8 units on a scale
Standard Deviation 16.4
|
-3.3 units on a scale
Standard Deviation 17.7
|
|
Change From Baseline in CFQ Scores - Adult Group
Emotion (N=99, 101, 105)
|
-1.1 units on a scale
Standard Deviation 11.5
|
-1.3 units on a scale
Standard Deviation 13.5
|
0.1 units on a scale
Standard Deviation 12.1
|
|
Change From Baseline in CFQ Scores - Adult Group
Social (N=99, 101, 106)
|
-1.1 units on a scale
Standard Deviation 12.3
|
-1.0 units on a scale
Standard Deviation 10.7
|
-0.8 units on a scale
Standard Deviation 11.1
|
|
Change From Baseline in CFQ Scores - Adult Group
Body (N=99,101, 106)
|
0.4 units on a scale
Standard Deviation 18.4
|
-0.9 units on a scale
Standard Deviation 15.3
|
1.7 units on a scale
Standard Deviation 16.4
|
|
Change From Baseline in CFQ Scores - Adult Group
Eat (N=99,101,106)
|
1.5 units on a scale
Standard Deviation 9.5
|
0.2 units on a scale
Standard Deviation 10.3
|
0.0 units on a scale
Standard Deviation 16.4
|
|
Change From Baseline in CFQ Scores - Adult Group
Treat (N=99, 101, 106)
|
0.9 units on a scale
Standard Deviation 15.5
|
-1.4 units on a scale
Standard Deviation 14.1
|
-1.7 units on a scale
Standard Deviation 12.7
|
|
Change From Baseline in CFQ Scores - Adult Group
Health (N=99, 101, 106)
|
-1.9 units on a scale
Standard Deviation 15.1
|
-3.2 units on a scale
Standard Deviation 18.3
|
-0.6 units on a scale
Standard Deviation 18.1
|
|
Change From Baseline in CFQ Scores - Adult Group
Weight (N=95, 101, 103)
|
1.4 units on a scale
Standard Deviation 22.2
|
-3.3 units on a scale
Standard Deviation 28.9
|
-0.0 units on a scale
Standard Deviation 26.0
|
|
Change From Baseline in CFQ Scores - Adult Group
Respirat (N=93, 101, 103)
|
-1.3 units on a scale
Standard Deviation 14.8
|
-3.7 units on a scale
Standard Deviation 15.8
|
-1.8 units on a scale
Standard Deviation 14.3
|
|
Change From Baseline in CFQ Scores - Adult Group
Digest (N=93, 101, 103)
|
0.8 units on a scale
Standard Deviation 14.9
|
-1.3 units on a scale
Standard Deviation 13.7
|
0.3 units on a scale
Standard Deviation 14.9
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents (age 6-13) with CF. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.
Outcome measures
| Measure |
Placebo
n=168 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=166 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=176 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Change From Baseline in CFQ Scores - Adolescents Group
Physical (N=46, 42, 54)
|
1.1 units on a scale
Standard Deviation 18.0
|
3.2 units on a scale
Standard Deviation 14.8
|
-1.9 units on a scale
Standard Deviation 15.0
|
|
Change From Baseline in CFQ Scores - Adolescents Group
School (N=46, 42, 55)
|
1.2 units on a scale
Standard Deviation 18.8
|
4.2 units on a scale
Standard Deviation 19.2
|
2.4 units on a scale
Standard Deviation 20.9
|
|
Change From Baseline in CFQ Scores - Adolescents Group
Body (N=46, 42, 55)
|
2.8 units on a scale
Standard Deviation 13.9
|
-0.3 units on a scale
Standard Deviation 16.1
|
-0.1 units on a scale
Standard Deviation 15.7
|
|
Change From Baseline in CFQ Scores - Adolescents Group
Eat (N=46, 42, 55)
|
-1.4 units on a scale
Standard Deviation 19.7
|
-2.4 units on a scale
Standard Deviation 17.3
|
1.6 units on a scale
Standard Deviation 22.8
|
|
Change From Baseline in CFQ Scores - Adolescents Group
Treat (N=46, 42, 55)
|
0.2 units on a scale
Standard Deviation 16.5
|
-1.9 units on a scale
Standard Deviation 20.1
|
5.7 units on a scale
Standard Deviation 19.5
|
|
Change From Baseline in CFQ Scores - Adolescents Group
Respirat (N=46, 42, 55)
|
-1.4 units on a scale
Standard Deviation 15.2
|
1.2 units on a scale
Standard Deviation 16.7
|
-3.0 units on a scale
Standard Deviation 20.2
|
|
Change From Baseline in CFQ Scores - Adolescents Group
Digest (N=46, 42, 55)
|
-5.1 units on a scale
Standard Deviation 26.3
|
2.4 units on a scale
Standard Deviation 26.9
|
-3.0 units on a scale
Standard Deviation 35.3
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement
The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents with CF - parent questionnaire. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.
Outcome measures
| Measure |
Placebo
n=168 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=166 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=176 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Eat (N=46, 43, 49)
|
-2.2 units on a scale
Standard Deviation 23.7
|
-0.8 units on a scale
Standard Deviation 21.2
|
3.4 units on a scale
Standard Deviation 15.9
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Body (N=46, 45, 52)
|
-3.9 units on a scale
Standard Deviation 18.6
|
-1.7 units on a scale
Standard Deviation 21.7
|
-3.2 units on a scale
Standard Deviation 22.6
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Treat (N=46, 45, 52)
|
-2.4 units on a scale
Standard Deviation 18.6
|
2.5 units on a scale
Standard Deviation 16.4
|
-0.2 units on a scale
Standard Deviation 21.4
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Physical (N=46, 45, 53)
|
-0.1 units on a scale
Standard Deviation 15.4
|
4.9 units on a scale
Standard Deviation 15.9
|
0.2 units on a scale
Standard Deviation 12.7
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Emotion (N=46, 45, 52)
|
-0.3 units on a scale
Standard Deviation 11.2
|
0.0 units on a scale
Standard Deviation 16.0
|
-0.1 units on a scale
Standard Deviation 15.7
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Vitality (N=46, 44, 53)
|
-0.1 units on a scale
Standard Deviation 12.3
|
3.3 units on a scale
Standard Deviation 13.1
|
-1.5 units on a scale
Standard Deviation 14.9
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
School (N=46, 45, 52)
|
-4.8 units on a scale
Standard Deviation 19.5
|
2.2 units on a scale
Standard Deviation 26.3
|
0.4 units on a scale
Standard Deviation 17.0
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Health (N=46, 45, 52)
|
-2.7 units on a scale
Standard Deviation 21.4
|
3.5 units on a scale
Standard Deviation 23.1
|
-3.0 units on a scale
Standard Deviation 20.7
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Respirat (N=45, 43, 50)
|
-2.8 units on a scale
Standard Deviation 16.4
|
-2.2 units on a scale
Standard Deviation 18.8
|
-6.0 units on a scale
Standard Deviation 14.2
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Digest (N=46, 43, 50)
|
-0.7 units on a scale
Standard Deviation 15.6
|
-1.8 units on a scale
Standard Deviation 17.0
|
1.1 units on a scale
Standard Deviation 16.8
|
|
Change From Baseline in CFQ Scores - Parent Questionnaire
Weight (N=45, 45, 49)
|
-5.2 units on a scale
Standard Deviation 35.5
|
1.5 units on a scale
Standard Deviation 30.1
|
4.1 units on a scale
Standard Deviation 31.6
|
SECONDARY outcome
Timeframe: pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dosePopulation: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement - patients \>= 12 years
Ae0-4,ss represents the amount of tiotropium that is eliminated in urine from time 0 to 4 hours at steady state
Outcome measures
| Measure |
Placebo
n=102 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=99 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Amount of Tiotropium Eliminated in Urine From 0 to 4 Hours at Steady State (Ae0-4,ss)
|
114 ng
Geometric Coefficient of Variation 73.0
|
245 ng
Geometric Coefficient of Variation 67.5
|
—
|
SECONDARY outcome
Timeframe: pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dosePopulation: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement - patients \>= 12 years
Cmax,ss represents the maximum measured concentration of tiotropium in plasma at steady state.
Outcome measures
| Measure |
Placebo
n=49 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=59 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Maximum Measured Concentration at Steady State (Cmax,ss)
|
6.49 pg/mL
Geometric Coefficient of Variation 58.5
|
9.95 pg/mL
Geometric Coefficient of Variation 66.6
|
—
|
SECONDARY outcome
Timeframe: pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dosePopulation: Full Analysis Set (FAS) includes all participants having a baseline measurement and at least one post-dose measurement - patients \>= 12 years
Tmax,ss represents the time from dosing to the maximum concentration of tiotropium in plasma
Outcome measures
| Measure |
Placebo
n=49 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=59 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Time From Dosing to the Maximum Concentration (Tmax,ss)
|
0.0830 h
Interval 0.033 to 0.433
|
0.0830 h
Interval 0.033 to 0.333
|
—
|
SECONDARY outcome
Timeframe: From first drug administration until 30 days after last drug administration (up to 121 days)Population: Treated set
Clinical Relevant Abnormalities for Vital Signs and Laboratory evaluation. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Event.
Outcome measures
| Measure |
Placebo
n=168 Participants
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=166 Participants
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=176 Participants
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
Blood chloride decreased
|
0 participants
|
0 participants
|
1 participants
|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
Blood glucose increased
|
1 participants
|
1 participants
|
0 participants
|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
Blood pressure increased
|
2 participants
|
1 participants
|
0 participants
|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
Blood sodium decreased
|
0 participants
|
0 participants
|
1 participants
|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
Eosinophil count increased
|
0 participants
|
1 participants
|
0 participants
|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
Hepatic enzyme increased
|
2 participants
|
0 participants
|
0 participants
|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
Oxygen saturation decreased
|
0 participants
|
0 participants
|
1 participants
|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
Vitamin K decreased
|
1 participants
|
0 participants
|
0 participants
|
|
Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation
White blood cell count increased
|
0 participants
|
1 participants
|
0 participants
|
Adverse Events
Placebo
Serious events: 21 serious events
Other events: 87 other events
Deaths: 0 deaths
Tiotropium Respimat 2.5 Micrograms
Serious events: 28 serious events
Other events: 95 other events
Deaths: 0 deaths
Tiotropium Respimat 5 Micrograms
Serious events: 21 serious events
Other events: 110 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=168 participants at risk
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=166 participants at risk
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=176 participants at risk
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Aplastic anaemia
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Congenital, familial and genetic disorders
Cystic fibrosis
|
3.0%
5/168
|
4.8%
8/166
|
4.5%
8/176
|
|
Congenital, familial and genetic disorders
Cystic fibrosis lung
|
4.2%
7/168
|
2.4%
4/166
|
2.3%
4/176
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/168
|
0.60%
1/166
|
0.57%
1/176
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
0.60%
1/168
|
0.00%
0/166
|
0.57%
1/176
|
|
Gastrointestinal disorders
Gastritis
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
0.00%
0/168
|
0.00%
0/166
|
0.57%
1/176
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/168
|
0.00%
0/166
|
0.57%
1/176
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.60%
1/168
|
0.00%
0/166
|
0.57%
1/176
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
General disorders
Application site hypersensitivity
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
General disorders
Infusion related reaction
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
General disorders
Multi-organ failure
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
General disorders
Systemic inflammatory response syndrome
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Infections and infestations
Bronchitis
|
1.2%
2/168
|
1.2%
2/166
|
0.00%
0/176
|
|
Infections and infestations
Bronchopneumonia
|
0.60%
1/168
|
0.60%
1/166
|
0.57%
1/176
|
|
Infections and infestations
Cellulitis
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Infections and infestations
Chronic sinusitis
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Infections and infestations
Lung infection
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Infections and infestations
Lung infection pseudomonal
|
0.60%
1/168
|
0.60%
1/166
|
0.57%
1/176
|
|
Infections and infestations
Oral herpes
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Infections and infestations
Overgrowth bacterial
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Infections and infestations
Pleurisy viral
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Infections and infestations
Pneumonia
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Infections and infestations
Pseudomonas infection
|
0.00%
0/168
|
0.60%
1/166
|
0.57%
1/176
|
|
Infections and infestations
Respiratory tract infection
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Infections and infestations
Sepsis
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Infections and infestations
Stenotrophomonas infection
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Investigations
Pulmonary function test decreased
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Metabolism and nutrition disorders
Hyperlipasaemia
|
0.00%
0/168
|
0.00%
0/166
|
0.57%
1/176
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Renal and urinary disorders
Renal disorder
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/168
|
0.60%
1/166
|
0.57%
1/176
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/168
|
0.00%
0/166
|
1.7%
3/176
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/168
|
1.2%
2/166
|
0.00%
0/176
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
0.00%
0/168
|
0.60%
1/166
|
0.00%
0/176
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
|
Surgical and medical procedures
Antibiotic prophylaxis
|
0.60%
1/168
|
0.00%
0/166
|
0.00%
0/176
|
Other adverse events
| Measure |
Placebo
n=168 participants at risk
Patients randomised to receive matching placebo
|
Tiotropium Respimat 2.5 Micrograms
n=166 participants at risk
Patients randomised to receive Tiotropium Respimat 2.5 micrograms once daily
|
Tiotropium Respimat 5 Micrograms
n=176 participants at risk
Patients randomised to receive Tiotropium Respimat 5.0 micrograms once daily
|
|---|---|---|---|
|
Congenital, familial and genetic disorders
Cystic fibrosis
|
7.1%
12/168
|
9.0%
15/166
|
9.7%
17/176
|
|
Gastrointestinal disorders
Abdominal pain
|
6.0%
10/168
|
7.8%
13/166
|
5.1%
9/176
|
|
General disorders
Pyrexia
|
10.1%
17/168
|
5.4%
9/166
|
10.2%
18/176
|
|
Infections and infestations
Bronchitis
|
4.2%
7/168
|
2.4%
4/166
|
5.7%
10/176
|
|
Infections and infestations
Nasopharyngitis
|
8.3%
14/168
|
6.6%
11/166
|
8.0%
14/176
|
|
Infections and infestations
Sinusitis
|
3.6%
6/168
|
1.8%
3/166
|
5.1%
9/176
|
|
Infections and infestations
Upper respiratory tract infection
|
3.6%
6/168
|
4.8%
8/166
|
6.2%
11/176
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.4%
9/168
|
3.0%
5/166
|
2.3%
4/176
|
|
Nervous system disorders
Headache
|
10.7%
18/168
|
4.2%
7/166
|
8.0%
14/176
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.2%
34/168
|
20.5%
34/166
|
26.1%
46/176
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.4%
9/168
|
4.8%
8/166
|
3.4%
6/176
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
4.2%
7/168
|
7.2%
12/166
|
6.2%
11/176
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.4%
4/168
|
5.4%
9/166
|
5.7%
10/176
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.7%
13/168
|
3.0%
5/166
|
6.2%
11/176
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.4%
9/168
|
3.6%
6/166
|
5.1%
9/176
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
4.8%
8/168
|
6.6%
11/166
|
7.4%
13/176
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER