Asthma
Conditions
Brief summary
The aim of the study is to evaluate efficacy and safety of a 48-week treatment with two doses of tiotropium bromide compared to placebo in adolescent patients with moderate persistent asthma. Efficacy and safety will be assessed by measuring lung function parameters and evaluating the effects on asthma exacerbations, on Quality of life, on health care resource utilisation an on the number of adverse events.
Interventions
DRUGtiotropium Respimat low dose
IMP
DRUGplacebo Respimat
placebo representing comparator
DRUGtiotropium Respimat high dose
IMP
Sponsors
Pfizer
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. All patients and their parents (or legally accepted caregiver) must sign and date an informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial. 2. Male or female patients between 12 and 17 years of age. 3. All patients must have at least a 3 months history of asthma at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at visit 1 with a bronchodilator reversibility test. 4. All patients must have been on maintenance treatment with inhaled corticosteroids at a stable medium dose for at least 4 weeks before Visit 1. 5. All patients must be symptomatic (partly controlled) at Visit 1 (screening) and at randomisation defined by an Asthma Control Questionnaire (ACQ) mean score of more than or equal to 1.5. 6. All patients must have a pre-bronchodilator FEV1 more than or equal to 60% and less than or equal to 90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 as compared to Visit 2 must be within ± 30%. 7. All patients must have an increase in FEV1 of equal or above 12% and 200 mL after 400 µg salbutamol (albuterol) at Visit 1. If patients in the lower age range (e.g., 12 to 14 year olds) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (12%) post-bronchodilator response. 8. All patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment. 9. Patients should be able to use the Respimat® inhaler correctly. 10. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres.
Exclusion criteria
1. Patients with a significant disease other than asthma. 2. Patients with clinically relevant abnormal screening haematology or blood chemistry 3. Patients with a history of congenital or acquired heart disease, and/or have been hospitalised for cardiac syncope or failure during the past year. 4. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year. 5. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. 6. Patients with lung diseases other than asthma (e.g. Cystic Fibrosis). In case of ex-premature infants, a history of significant bronchopulmonary dysplasia will be regarded as exclusion criterion. 7. Patients with known active tuberculosis. 8. Patients with significant alcohol or drug abuse within the past two years. 9. Patients who have undergone thoracotomy with pulmonary resection. 10. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1). 11. Patients with known hypersensitivity to anticholinergic drugs, Benzalkonium chloride (BAC), Ethylenediaminetetraacetic acis (EDTA) or any other components of the tiotropium inhalation solution. 12. Pregnant or nursing adolescent female patients 13. Sexually active female patients of child-bearing potential not using a highly effective method of birth control. 14. Patients who have taken an investigational drug within 4 weeks prior to Visit 1. 15. Patients who have been treated with long-acting anticholinergics (e.g. tiotropium -Spiriva) within four weeks prior to screening (Visit 1). 16. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation. 17. Patients who have been treated with Anti-IgE treatment (Omalizumab Xolair) within the last 6 months prior to screening. 18. Patients who have been treated with systemic (oral or intravenous) corticosteroids within 4 weeks prior to screening (Visit 1). 19. Patients who have been treated with long-acting theophylline preparations within 2 weeks prior to screening (Visit 1) or during the run-in period 20. Patients who have been treated with other non-approved and according to international guidelines not recommended ¿experimental¿ drugs for routine asthma therapy. 21. Patients with any acute asthma exacerbation or respiratory tract infection in the 4 weeks prior to Visit 1. 22. Patients requiring 10 or more puffs of rescue medication (salbutamol/albuterol) per day on more than 2 consecutive days during the run-in period. 23. Patients who have previously been randomised in this trial or are currently participating in another study. 24. Patients who are being treated with oral beta-blocker medication. 25. Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated. 26. Patients with renal impairment, as defined by a creatinine clearance less than 50 mL/min/1.73 m2 Body Surface Area as calculated by Schwartz formula.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 peak0-3 Change From Baseline | Baseline and 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FVC peak0-3 Change From Baseline | Baseline and 24 weeks | 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. |
| Trough FVC Change From Baseline | Baseline and 24 weeks | 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.. |
| FEV1 AUC (0-3h) Change From Baseline | Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks | 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. |
| FVC AUC (0-3h) Change From Baseline | Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks | 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. |
| FEF25-75 Change From Baseline | Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks | 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. |
| Use of PRN Rescue Medication During the Daytime | Baseline and Week 24 | 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. |
| Use of PRN Rescue Medication During the Night-time | Baseline and week 24 | 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. |
| Trough FEV1 Change From Baseline | Baseline and 24 weeks | 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. |
| Control of Asthma as Assessed by ACQ Total Score | Baseline and week 24 | 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. |
| ACQ Total Score Responders | Week 24 | 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. |
| Control of Asthma as Assessed by ACQ6 | Baseline and week 24 | 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. |
| ACQ6 Responders | Week 24 | 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 to First Severe Asthma Exacerbation During the 48 Week Treatment Period | 48 weeks | 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 to First Asthma Exacerbation During the 48 Week Treatment Period | Week 48 | 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. |
| Use of PRN Rescue Medication During the Day | Baseline and week 24 | 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. |
Countries
Chile, Germany, Hungary, Italy, Latvia, Mexico, Russia, Slovakia, South Korea, Spain, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Respimat Inhalation of placebo solution once daily for 48 weeks, delivered by the Respimat Inhaler | 138 |
| Tio R2.5 Inhalation of 2.5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler | 125 |
| Tio R5 Inhalation of 5μg tiotropium bromide solution once daily for 48 weeks, delivered by the Respimat Inhaler | 134 |
| Total | 397 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Not Treated | 0 | 0 | 1 |
| Overall Study | Other reason not defined above | 1 | 5 | 3 |
| Overall Study | Protocol Violation | 3 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo Respimat | Tio R2.5 | Tio R5 | Total |
|---|---|---|---|---|
| Age, Continuous | 14.2 years STANDARD_DEVIATION 1.7 | 14.2 years STANDARD_DEVIATION 1.8 | 14.5 years STANDARD_DEVIATION 1.6 | 14.3 years STANDARD_DEVIATION 1.7 |
| Sex: Female, Male Female | 50 Participants | 44 Participants | 45 Participants | 139 Participants |
| Sex: Female, Male Male | 88 Participants | 81 Participants | 89 Participants | 258 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 62 / 138 | 55 / 125 | 61 / 134 |
| serious Total, serious adverse events | 2 / 138 | 2 / 125 | 3 / 134 |
Outcome results
Primary
FEV1 peak0-3 Change From Baseline
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | FEV1 peak0-3 Change From Baseline | 0.373 Litres | Standard Error 0.037 |
| Tio R2.5 | FEV1 peak0-3 Change From Baseline | 0.507 Litres | Standard Error 0.04 |
| Tio R5 | FEV1 peak0-3 Change From Baseline | 0.547 Litres | Standard Error 0.038 |
p-value: 0.008595% CI: [0.034, 0.234]Mixed Models Analysis
p-value: 0.000595% CI: [0.076, 0.272]Mixed Models Analysis
Secondary
ACQ6 Responders
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
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Respimat | ACQ6 Responders | No change | 22.5 percentage of participants |
| Placebo Respimat | ACQ6 Responders | Responder | 69.6 percentage of participants |
| Placebo Respimat | ACQ6 Responders | Worsening | 8.0 percentage of participants |
| Tio R2.5 | ACQ6 Responders | No change | 20.0 percentage of participants |
| Tio R2.5 | ACQ6 Responders | Responder | 76.8 percentage of participants |
| Tio R2.5 | ACQ6 Responders | Worsening | 3.2 percentage of participants |
| Tio R5 | ACQ6 Responders | Responder | 72.4 percentage of participants |
| Tio R5 | ACQ6 Responders | Worsening | 4.5 percentage of participants |
| Tio R5 | ACQ6 Responders | No change | 23.1 percentage of participants |
Secondary
ACQ Total Score Responders
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
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Respimat | ACQ Total Score Responders | Responder | 66.7 percentage of participants |
| Placebo Respimat | ACQ Total Score Responders | No change | 27.5 percentage of participants |
| Placebo Respimat | ACQ Total Score Responders | Worsening | 5.8 percentage of participants |
| Tio R2.5 | ACQ Total Score Responders | Worsening | 2.4 percentage of participants |
| Tio R2.5 | ACQ Total Score Responders | No change | 21.6 percentage of participants |
| Tio R2.5 | ACQ Total Score Responders | Responder | 76.0 percentage of participants |
| Tio R5 | ACQ Total Score Responders | No change | 23.1 percentage of participants |
| Tio R5 | ACQ Total Score Responders | Responder | 74.6 percentage of participants |
| Tio R5 | ACQ Total Score Responders | Worsening | 2.2 percentage of participants |
Secondary
Control of Asthma as Assessed by ACQ6
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
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | Control of Asthma as Assessed by ACQ6 | 1.173 units on a scale | Standard Error 0.068 |
| Tio R2.5 | Control of Asthma as Assessed by ACQ6 | 1.026 units on a scale | Standard Error 0.073 |
| Tio R5 | Control of Asthma as Assessed by ACQ6 | 1.119 units on a scale | Standard Error 0.07 |
p-value: 0.1295% CI: [-0.333, 0.038]Mixed Models Analysis
p-value: 0.558995% CI: [-0.235, 0.127]Mixed Models Analysis
Secondary
Control of Asthma as Assessed by ACQ Total Score
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
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | Control of Asthma as Assessed by ACQ Total Score | 1.213 Units on a scale | Standard Error 0.062 |
| Tio R2.5 | Control of Asthma as Assessed by ACQ Total Score | 1.053 Units on a scale | Standard Error 0.067 |
| Tio R5 | Control of Asthma as Assessed by ACQ Total Score | 1.116 Units on a scale | Standard Error 0.064 |
p-value: 0.065395% CI: [-0.33, 0.01]Mixed Models Analysis
p-value: 0.251695% CI: [-0.263, 0.069]Mixed Models Analysis
Secondary
FEF25-75 Change From Baseline
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | FEF25-75 Change From Baseline | 2 hours post-dose | 0.403 Litres per second | Standard Error 0.069 |
| Placebo Respimat | FEF25-75 Change From Baseline | 1 hour post-dose | 0.359 Litres per second | Standard Error 0.067 |
| Placebo Respimat | FEF25-75 Change From Baseline | 10 minutes pre-dose (n=137, 119, 131) | 0.332 Litres per second | Standard Error 0.072 |
| Placebo Respimat | FEF25-75 Change From Baseline | 30 minutes post-dose | 0.372 Litres per second | Standard Error 0.066 |
| Placebo Respimat | FEF25-75 Change From Baseline | 3 hours post-dose | 0.347 Litres per second | Standard Error 0.068 |
| Tio R2.5 | FEF25-75 Change From Baseline | 1 hour post-dose | 0.596 Litres per second | Standard Error 0.072 |
| Tio R2.5 | FEF25-75 Change From Baseline | 10 minutes pre-dose (n=137, 119, 131) | 0.461 Litres per second | Standard Error 0.079 |
| Tio R2.5 | FEF25-75 Change From Baseline | 30 minutes post-dose | 0.536 Litres per second | Standard Error 0.072 |
| Tio R2.5 | FEF25-75 Change From Baseline | 2 hours post-dose | 0.615 Litres per second | Standard Error 0.075 |
| Tio R2.5 | FEF25-75 Change From Baseline | 3 hours post-dose | 0.653 Litres per second | Standard Error 0.074 |
| Tio R5 | FEF25-75 Change From Baseline | 3 hours post-dose | 0.850 Litres per second | Standard Error 0.07 |
| Tio R5 | FEF25-75 Change From Baseline | 2 hours post-dose | 0.857 Litres per second | Standard Error 0.071 |
| Tio R5 | FEF25-75 Change From Baseline | 10 minutes pre-dose (n=137, 119, 131) | 0.609 Litres per second | Standard Error 0.074 |
| Tio R5 | FEF25-75 Change From Baseline | 1 hour post-dose | 0.835 Litres per second | Standard Error 0.069 |
| Tio R5 | FEF25-75 Change From Baseline | 30 minutes post-dose | 0.763 Litres per second | Standard Error 0.068 |
Secondary
FEV1 AUC (0-3h) Change From Baseline
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | FEV1 AUC (0-3h) Change From Baseline | 0.281 Litres | Standard Error 0.035 |
| Tio R2.5 | FEV1 AUC (0-3h) Change From Baseline | 0.411 Litres | Standard Error 0.038 |
| Tio R5 | FEV1 AUC (0-3h) Change From Baseline | 0.463 Litres | Standard Error 0.036 |
p-value: 0.007995% CI: [0.034, 0.225]Mixed Models Analysis
p-value: 0.000295% CI: [0.088, 0.275]Mixed Models Analysis
Secondary
FVC AUC (0-3h) Change From Baseline
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | FVC AUC (0-3h) Change From Baseline | 0.240 Litres | Standard Error 0.039 |
| Tio R2.5 | FVC AUC (0-3h) Change From Baseline | 0.330 Litres | Standard Error 0.042 |
| Tio R5 | FVC AUC (0-3h) Change From Baseline | 0.311 Litres | Standard Error 0.04 |
p-value: 0.094595% CI: [-0.016, 0.196]Mixed Models Analysis
p-value: 0.175595% CI: [-0.032, 0.175]Mixed Models Analysis
Secondary
FVC peak0-3 Change From Baseline
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | FVC peak0-3 Change From Baseline | 0.331 Litres | Standard Error 0.041 |
| Tio R2.5 | FVC peak0-3 Change From Baseline | 0.419 Litres | Standard Error 0.045 |
| Tio R5 | FVC peak0-3 Change From Baseline | 0.403 Litres | Standard Error 0.043 |
p-value: 0.123195% CI: [-0.024, 0.2]Mixed Models Analysis
p-value: 0.19595% CI: [-0.037, 0.182]Mixed Models Analysis
Secondary
Time to First Asthma Exacerbation During the 48 Week Treatment Period
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
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Respimat | Time to First Asthma Exacerbation During the 48 Week Treatment Period | 37 Participants |
| Tio R2.5 | Time to First Asthma Exacerbation During the 48 Week Treatment Period | 34 Participants |
| Tio R5 | Time to First Asthma Exacerbation During the 48 Week Treatment Period | 30 Participants |
p-value: 0.8795% CI: [0.65, 1.66]Regression, Cox
p-value: 0.419895% CI: [0.51, 1.33]Regression, Cox
Secondary
Time to First Severe Asthma Exacerbation During the 48 Week Treatment Period
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
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Respimat | Time to First Severe Asthma Exacerbation During the 48 Week Treatment Period | 9 Participants |
| Tio R2.5 | Time to First Severe Asthma Exacerbation During the 48 Week Treatment Period | 5 Participants |
| Tio R5 | Time to First Severe Asthma Exacerbation During the 48 Week Treatment Period | 2 Participants |
p-value: 0.402395% CI: [0.21, 1.87]Regression, Cox
p-value: 0.06295% CI: [0.05, 1.08]Regression, Cox
Secondary
Trough FEV1 Change From Baseline
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | Trough FEV1 Change From Baseline | 0.283 Litres | Standard Error 0.04 |
| Tio R2.5 | Trough FEV1 Change From Baseline | 0.367 Litres | Standard Error 0.044 |
| Tio R5 | Trough FEV1 Change From Baseline | 0.400 Litres | Standard Error 0.041 |
p-value: 0.130795% CI: [-0.025, 0.194]Mixed Models Analysis
p-value: 0.03295% CI: [0.01, 0.223]Mixed Models Analysis
Secondary
Trough FVC Change From Baseline
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | Trough FVC Change From Baseline | 0.281 Litres | Standard Error 0.043 |
| Tio R2.5 | Trough FVC Change From Baseline | 0.345 Litres | Standard Error 0.047 |
| Tio R5 | Trough FVC Change From Baseline | 0.316 Litres | Standard Error 0.045 |
p-value: 0.292195% CI: [-0.055, 0.181]Mixed Models Analysis
p-value: 0.549595% CI: [-0.08, 0.15]Mixed Models Analysis
Secondary
Use of PRN Rescue Medication During the Day
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
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | Use of PRN Rescue Medication During the Day | -0.524 Number of puffs of rescue medication | Standard Error 0.098 |
| Tio R2.5 | Use of PRN Rescue Medication During the Day | -0.556 Number of puffs of rescue medication | Standard Error 0.104 |
| Tio R5 | Use of PRN Rescue Medication During the Day | -0.480 Number of puffs of rescue medication | Standard Error 0.1 |
p-value: 0.825395% CI: [-0.312, 0.249]Mixed Models Analysis
p-value: 0.755995% CI: [-0.232, 0.319]Mixed Models Analysis
Secondary
Use of PRN Rescue Medication During the Daytime
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
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | Use of PRN Rescue Medication During the Daytime | -0.206 Number of puffs of rescue medication | Standard Error 0.066 |
| Tio R2.5 | Use of PRN Rescue Medication During the Daytime | -0.209 Number of puffs of rescue medication | Standard Error 0.071 |
| Tio R5 | Use of PRN Rescue Medication During the Daytime | -0.215 Number of puffs of rescue medication | Standard Error 0.068 |
p-value: 0.97695% CI: [-0.184, 0.178]Mixed Models Analysis
p-value: 0.922495% CI: [-0.186, 0.168]Mixed Models Analysis
Secondary
Use of PRN Rescue Medication During the Night-time
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
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | Use of PRN Rescue Medication During the Night-time | -0.144 Number of puffs of rescue medication | Standard Error 0.059 |
| Tio R2.5 | Use of PRN Rescue Medication During the Night-time | -0.122 Number of puffs of rescue medication | Standard Error 0.064 |
| Tio R5 | Use of PRN Rescue Medication During the Night-time | -0.032 Number of puffs of rescue medication | Standard Error 0.061 |
p-value: 0.785295% CI: [-0.14, 0.185]Mixed Models Analysis
p-value: 0.164995% CI: [-0.046, 0.271]Mixed Models Analysis