Asthma
Conditions
Brief summary
The overall purpose of the trial is to evaluate efficacy and safety of tiotropium inhalation solution delivered via Respimat® inhaler (2.5 mcg and 5 mcg once daily in the evening) over 48 weeks, compared to placebo, in children (6 to 11 years old) with moderate persistent asthma.
Interventions
DRUGTiotropium low dose QD
2 actuations once daily in the evening
DRUGTiotropium high dose QD
2 actuations once daily in the evening
DRUGPlacebo
2 actuations once daily in the evening
Sponsors
Pfizer
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria are: 1. All patients' parent(s) (or legal guardian) must sign and date an informed consent prior to participation in the trial. In addition, an informed assent suitable for this age group has to be obtained from patients. A separate informed consent/assent is required for pharmacogenomic sampling. 2. Male or female patients between 6 and 11 years of age. 3. All patients must have at least a 6-month history of asthma. 4. All patients must have been on maintenance treatment with an inhaled corticosteroid at a stable medium dose, either as mono treatment or in combination with another controller medication, for at least 4 weeks before Visit 1. While the LTRA is permitted throughout the trial, the LABA has to be stopped at least 24 hours prior to Visit 1, as no LABAs are permitted during screening and treatment period of this trial. 5. All patients must be symptomatic (partly controlled) at Visit 1 and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ-IA) mean score \>= 1.5. 6. All patients must have a pre-bronchodilator forced expiratory volume in one second (FEV1) \>= 60% and =\< 90% of predicted normal at Visit 1. 7. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%) as compared to Visit 2 (pre-dose) must be within ± 30%. 8. All patients must confirm the diagnosis of asthma by bronchodilator reversibility at Visit 1, resulting in an increase in FEV1 of \>= 12%, 15 to 30 minutes after 200 mcg salbutamol/albuterol. 9. Patients must be able to use the Respimat inhaler correctly. 10. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter (diary compliance of at least 80% is required).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Peak (0-3h) Change From Baseline | Baseline and 24 Weeks. | Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 24. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Peak (0-3h) at Week 48 Change From Baseline | Baseline and Week 48. | Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest. |
| 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 week 24 | Change from baseline of area under the curve (AUC) from 0 to 3 hours 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). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest. |
| FEV1 Change From Baseline at Each Individual Timepoint | Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks | FEV1 change from baseline to week 24 at each individual timepoint. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| FVC Peak(0-3h) Change From Baseline | Baseline and Week 24, Baseline and Week 48. | Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak(0-3h)) after 24 and 48 Weeks of treatment. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Trough FVC Change From Baseline | Baseline and Week 24, Baseline and Week 48 | Change from baseline in Trough (pre-dose) FVC measured at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| 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 hours for FVC (Forced vital capacity) (FVC AUC (0-3h)) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest. |
| FVC Change From Baseline at Each Individual Timepoint | Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at Week 24 | FVC change from baseline to week 24 at each individual timepoint. The measured values presented are actually adjusted means The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Use of PRN (Pro re Nata) Rescue Medication Per Day | Baseline and Week 24, Baseline and Week 48. | Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used per day (24 hour period) based on the weekly mean at weeks 24 and 48. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Use of PRN Rescue Medication During Daytime | Baseline and Week 24, Baseline and Week 48. | Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during daytime based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Use of PRN Rescue Medication During Nighttime | Baseline and Week 24, Baseline and Week 48. | Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during nighttime based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Peak Expiratory Flow (PEF) a.m. Change From Baseline | Baseline and Week 24, Baseline and Week 48. | Change from baseline in the morning (a.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| PEF p.m. Change From Baseline | Baseline and Week 24, Baseline and Week 48. | Change from baseline in the evening (p.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| PEF Variability Change From Baseline | Baseline and Week 24, Baseline and Week 48. | Change from baseline in the peak expiratory flow variability based on the weekly mean at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| FEV1 a.m Change From Baseline | Baseline and Week 24, Baseline and Week 48. | Change from baseline in morning (a.m.) FEV1 based on the weekly mean at week 24 and 48. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Trough FEV1 Change From Baseline | Baseline and Week 24, Baseline and Week 48. | Change from Baseline in Trough (pre-dose) Forced Expiratory Volume (FEV) in 1 second (FEV1) measured at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| ACQ-IA Total Score | Weeks 24 and 48. | Interviewer Administered Asthma Control Questionnaire (ACQ-IA) total score after 24 and 48 weeks of treatment. The ACQ-IA 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-IA total score is calculated as the mean of the responses to all 7 questions. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| ACQ-IA Responder Analysis | Weeks 24 and 48 | Responder categories based on the ACQ-IA total score after 24 and 48 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). No statistical testing was performed for ACQ-IA total score responders. The ACQ-IA 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. |
| PAQLQ(S) Total Score | Weeks 24 and 48. | Standardised Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S)) total score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). Total Score is calculated as mean of all 23 questions. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| PAQLQ(S) Symptom Domain Score | Weeks 24 and 48. | PAQLQ(S) symptom domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score was calculated as the mean of the items in the domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| PAQLQ(S) Activity Limitation Domain Score | Weeks 24 and 48. | PAQLQ(S) activity limitation domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| PAQLQ(S) Emotional Function Domain Score | Weeks 24 and 48. | PAQLQ(S) emotional function domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Responders in PAQLQ(S) at Weeks 24 and 48 | Weeks 24 and 48. | Responders in PAQLQ(S) at weeks 24 and 48. 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). No statistical testing was performed for PAQLQ(S) total score responders. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). |
| Change From Baseline in Nighttime Awakenings | Baseline and Week 24, Baseline and Week 48. | Change from baseline in nighttime awakenings based on the weekly mean at weeks 24 and 48. Nighttime awakenings was assessed by the question Did you wake up during the night due to your asthma? from the e-diary. Scores range from 1 (did not wake up) to 5 (was awake all night). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Change From Baseline in Morning Asthma Symptoms | Baseline and Week 24, Baseline and Week 48. | Change from baseline in morning asthma symptoms based on the weekly mean at weeks 24 and 48. Morning asthma symptoms was assessed by the question how were your asthma symptoms this morning? from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Change From Baseline in Daytime Asthma Symptoms | Baseline and Week 24, Baseline and Week 48. | Change from baseline in daytime asthma symptoms based on the weekly mean at weeks 24 and 48. Daytime asthma symptoms was assessed by the question how were your asthma symptoms during the day? from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Change From Baseline in Daytime Activity Limitations | Baseline and Week 24, Baseline and Week 48. | Change from baseline in daytime activity limitations based on the weekly mean at weeks 24 and 48. Daytime activity limitations was assessed by the question how limited were you in your activities today because of your asthma? from the e-diary. Scores range from 1 (not limited) to 5 (totally limited). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Change From Baseline in Daytime Experiences of Shortness of Breath | Baseline and Week 24, Baseline and Week 48. | Change from baseline in daytime experiences of shortness of breath based on the weekly mean at weeks 24 and 48. Daytime experiences of shortness of breath was assessed by the question how much shortness of breath did you experience during the day from the e-diary. Scores range from 1 (none) to 5 (a very great deal). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Change From Baseline in Daytime Experiences of Wheeze or Cough | Baseline and Week 24, Baseline and Week 48. | Change from baseline in daytime experiences of wheeze or cough based on the weekly mean at weeks 24 and 48. Daytime experiences of wheeze or cough was assessed by the question did you experience wheeze or cough during the day? from the e-diary. Scores range from 1 (not at all) to 5 (all the time). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| Change From Baseline in Asthma Symptom-free Days | Baseline and Week 24, Baseline and Week 48. | Change from baseline in asthma symptom-free days based on the weekly mean at weeks 24 and 48. A day was considered as an asthma symptom-free day if there were no symptoms reported via the e-Diary (electronic diary) and no use of rescue medication reported via the eDiary during that day. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
| FEV1 p.m. Change From Baseline | Baseline and Week 24, Baseline and Week 48. | Change from baseline in evening (p.m.) FEV1 based on the weekly mean at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint. |
Countries
Bulgaria, Canada, Germany, Guatemala, Hungary, Latvia, Lithuania, Norway, Portugal, Romania, Russia, South Korea, Sweden, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Respimat Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care. | 131 |
| Tio R2.5 Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care. | 135 |
| Tio R5 Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care. | 135 |
| Total | 401 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Consent withdrawn not due to AE | 4 | 3 | 2 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 |
| Overall Study | Non compliant with protocol | 1 | 0 | 0 |
| Overall Study | Not treated | 1 | 1 | 0 |
| Overall Study | Other | 4 | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo Respimat | Tio R2.5 | Tio R5 | Total |
|---|---|---|---|---|
| Age, Continuous | 9.0 Years STANDARD_DEVIATION 1.6 | 9.0 Years STANDARD_DEVIATION 1.6 | 8.9 Years STANDARD_DEVIATION 1.7 | 8.9 Years STANDARD_DEVIATION 1.6 |
| Sex: Female, Male Female | 46 Participants | 38 Participants | 53 Participants | 137 Participants |
| Sex: Female, Male Male | 85 Participants | 97 Participants | 82 Participants | 264 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 | 79 / 131 | 76 / 135 | 71 / 135 |
| serious Total, serious adverse events | 6 / 131 | 3 / 135 | 1 / 135 |
Outcome results
Primary
FEV1 Peak (0-3h) Change From Baseline
Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 24. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Time frame: Baseline and 24 Weeks.
Population: Full Analysis Set (FAS) was equal to treated set which included all randomised patients who received at least 1 documented dose of study medication. Missing data at a visit was imputed by available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | FEV1 Peak (0-3h) Change From Baseline | 0.225 Litres (L) | Standard Error 0.027 |
| Tio R2.5 | FEV1 Peak (0-3h) Change From Baseline | 0.395 Litres (L) | Standard Error 0.026 |
| Tio R5 | FEV1 Peak (0-3h) Change From Baseline | 0.389 Litres (L) | Standard Error 0.026 |
Comparison: Stepwise testing of the null hypothesis was used to test the efficacy of Tio R5 and then Tio R2.5, each over placebo. The analysis was performed in a stepwise manner, firstly for this endpoint, then Trough FEV1. Each step was only considered confirmatory if all previous steps were successful.p-value: <0.000195% CI: [0.108, 0.231]Mixed Models Analysis
Comparison: Stepwise testing of the null hypothesis was used to test the efficacy of Tio R5 and then Tio R2.5, each over placebo. The analysis was performed in a stepwise manner, firstly for this endpoint, then Trough FEV1. Each step was only considered confirmatory if all previous steps were successful.p-value: <0.000195% CI: [0.103, 0.255]Mixed Models Analysis
Secondary
ACQ-IA Responder Analysis
Responder categories based on the ACQ-IA total score after 24 and 48 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). No statistical testing was performed for ACQ-IA total score responders. The ACQ-IA 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: Weeks 24 and 48
Population: FAS, missing data for patients not withdrawn from the study were either categorised as no change or based on available data, withdrawn patients were imputed based upon discontinuation reason
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Respimat | ACQ-IA Responder Analysis | Responders at Week 24 | 97 Patients |
| Placebo Respimat | ACQ-IA Responder Analysis | No Change at Week 24 | 34 Patients |
| Placebo Respimat | ACQ-IA Responder Analysis | Worsening at Week 24 | 0 Patients |
| Placebo Respimat | ACQ-IA Responder Analysis | Responder at Week 48 | 114 Patients |
| Placebo Respimat | ACQ-IA Responder Analysis | No Change at Week 48 | 16 Patients |
| Placebo Respimat | ACQ-IA Responder Analysis | Worsening at Week 48 | 1 Patients |
| Tio R2.5 | ACQ-IA Responder Analysis | Worsening at Week 48 | 3 Patients |
| Tio R2.5 | ACQ-IA Responder Analysis | Responders at Week 24 | 108 Patients |
| Tio R2.5 | ACQ-IA Responder Analysis | Responder at Week 48 | 118 Patients |
| Tio R2.5 | ACQ-IA Responder Analysis | No Change at Week 48 | 14 Patients |
| Tio R2.5 | ACQ-IA Responder Analysis | No Change at Week 24 | 27 Patients |
| Tio R2.5 | ACQ-IA Responder Analysis | Worsening at Week 24 | 0 Patients |
| Tio R5 | ACQ-IA Responder Analysis | No Change at Week 24 | 16 Patients |
| Tio R5 | ACQ-IA Responder Analysis | Worsening at Week 24 | 1 Patients |
| Tio R5 | ACQ-IA Responder Analysis | Worsening at Week 48 | 1 Patients |
| Tio R5 | ACQ-IA Responder Analysis | Responder at Week 48 | 117 Patients |
| Tio R5 | ACQ-IA Responder Analysis | Responders at Week 24 | 118 Patients |
| Tio R5 | ACQ-IA Responder Analysis | No Change at Week 48 | 17 Patients |
Secondary
ACQ-IA Total Score
Interviewer Administered Asthma Control Questionnaire (ACQ-IA) total score after 24 and 48 weeks of treatment. The ACQ-IA 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-IA total score is calculated as the mean of the responses to all 7 questions. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Weeks 24 and 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | ACQ-IA Total Score | Week 24 (N=126, 131, 134) | 1.017 Units on a Scale | Standard Error 0.062 |
| Placebo Respimat | ACQ-IA Total Score | Week 48 (N=124, 130, 130) | 0.817 Units on a Scale | Standard Error 0.062 |
| Tio R2.5 | ACQ-IA Total Score | Week 24 (N=126, 131, 134) | 0.897 Units on a Scale | Standard Error 0.06 |
| Tio R2.5 | ACQ-IA Total Score | Week 48 (N=124, 130, 130) | 0.752 Units on a Scale | Standard Error 0.06 |
| Tio R5 | ACQ-IA Total Score | Week 24 (N=126, 131, 134) | 0.835 Units on a Scale | Standard Error 0.06 |
| Tio R5 | ACQ-IA Total Score | Week 48 (N=124, 130, 130) | 0.723 Units on a Scale | Standard Error 0.061 |
Comparison: Week 24p-value: 0.097595% CI: [-0.262, 0.022]Mixed Models Analysis
Comparison: Week 24p-value: 0.011695% CI: [-0.323, -0.041]Mixed Models Analysis
Comparison: Week 48p-value: 0.373295% CI: [-0.208, 0.078]Mixed Models Analysis
Comparison: Week 48p-value: 0.198595% CI: [-0.236, 0.049]Mixed Models Analysis
Secondary
Change From Baseline in Asthma Symptom-free Days
Change from baseline in asthma symptom-free days based on the weekly mean at weeks 24 and 48. A day was considered as an asthma symptom-free day if there were no symptoms reported via the e-Diary (electronic diary) and no use of rescue medication reported via the eDiary during that day. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Change From Baseline in Asthma Symptom-free Days | Week 24 (N=122, 130, 133) | 0.135 Days | Standard Error 0.036 |
| Placebo Respimat | Change From Baseline in Asthma Symptom-free Days | Week 48 (N=120, 123, 127) | 0.151 Days | Standard Error 0.036 |
| Tio R2.5 | Change From Baseline in Asthma Symptom-free Days | Week 24 (N=122, 130, 133) | 0.176 Days | Standard Error 0.034 |
| Tio R2.5 | Change From Baseline in Asthma Symptom-free Days | Week 48 (N=120, 123, 127) | 0.170 Days | Standard Error 0.035 |
| Tio R5 | Change From Baseline in Asthma Symptom-free Days | Week 24 (N=122, 130, 133) | 0.172 Days | Standard Error 0.035 |
| Tio R5 | Change From Baseline in Asthma Symptom-free Days | Week 48 (N=120, 123, 127) | 0.180 Days | Standard Error 0.035 |
Comparison: Week 24p-value: 0.337595% CI: [-0.043, 0.125]Mixed Models Analysis
Comparison: Week 24p-value: 0.38895% CI: [-0.047, 0.121]Mixed Models Analysis
Comparison: Week 48p-value: 0.654195% CI: [-0.066, 0.104]Mixed Models Analysis
Comparison: Week 48p-value: 0.508995% CI: [-0.056, 0.133]Mixed Models Analysis
Secondary
Change From Baseline in Daytime Activity Limitations
Change from baseline in daytime activity limitations based on the weekly mean at weeks 24 and 48. Daytime activity limitations was assessed by the question how limited were you in your activities today because of your asthma? from the e-diary. Scores range from 1 (not limited) to 5 (totally limited). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Change From Baseline in Daytime Activity Limitations | Week 24 (N=121, 130, 133) | -0.181 Units on a scale | Standard Error 0.039 |
| Placebo Respimat | Change From Baseline in Daytime Activity Limitations | Week 48 (N=119, 123, 125) | -0.227 Units on a scale | Standard Error 0.039 |
| Tio R2.5 | Change From Baseline in Daytime Activity Limitations | Week 24 (N=121, 130, 133) | -0.212 Units on a scale | Standard Error 0.038 |
| Tio R2.5 | Change From Baseline in Daytime Activity Limitations | Week 48 (N=119, 123, 125) | -0.238 Units on a scale | Standard Error 0.038 |
| Tio R5 | Change From Baseline in Daytime Activity Limitations | Week 24 (N=121, 130, 133) | -0.240 Units on a scale | Standard Error 0.038 |
| Tio R5 | Change From Baseline in Daytime Activity Limitations | Week 48 (N=119, 123, 125) | -0.259 Units on a scale | Standard Error 0.038 |
Comparison: Week 24p-value: 0.500495% CI: [-0.122, 0.06]Mixed Models Analysis
Comparison: Week 24p-value: 0.198295% CI: [-0.149, 0.031]Mixed Models Analysis
Comparison: Week 48p-value: 0.801995% CI: [-0.103, 0.08]Mixed Models Analysis
Comparison: Week 48p-value: 0.487295% CI: [-0.123, 0.059]Mixed Models Analysis
Secondary
Change From Baseline in Daytime Asthma Symptoms
Change from baseline in daytime asthma symptoms based on the weekly mean at weeks 24 and 48. Daytime asthma symptoms was assessed by the question how were your asthma symptoms during the day? from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Change From Baseline in Daytime Asthma Symptoms | Week 24 (N=121, 130, 133) | -0.204 Units on a scale | Standard Error 0.041 |
| Placebo Respimat | Change From Baseline in Daytime Asthma Symptoms | Week 48 (N=119, 123, 125) | -0.261 Units on a scale | Standard Error 0.042 |
| Tio R2.5 | Change From Baseline in Daytime Asthma Symptoms | Week 24 (N=121, 130, 133) | -0.243 Units on a scale | Standard Error 0.04 |
| Tio R2.5 | Change From Baseline in Daytime Asthma Symptoms | Week 48 (N=119, 123, 125) | -0.272 Units on a scale | Standard Error 0.041 |
| Tio R5 | Change From Baseline in Daytime Asthma Symptoms | Week 24 (N=121, 130, 133) | -0.263 Units on a scale | Standard Error 0.04 |
| Tio R5 | Change From Baseline in Daytime Asthma Symptoms | Week 48 (N=119, 123, 125) | -0.312 Units on a scale | Standard Error 0.041 |
Comparison: Week 24p-value: 0.435995% CI: [-0.135, 0.058]Mixed Models Analysis
Comparison: Week 24p-value: 0.229395% CI: [-0.155, 0.037]Mixed Models Analysis
Comparison: Week 48p-value: 0.837295% CI: [-0.108, 0.088]Mixed Models Analysis
Comparison: Week 48p-value: 0.302295% CI: [-0.148, 0.046]Mixed Models Analysis
Secondary
Change From Baseline in Daytime Experiences of Shortness of Breath
Change from baseline in daytime experiences of shortness of breath based on the weekly mean at weeks 24 and 48. Daytime experiences of shortness of breath was assessed by the question how much shortness of breath did you experience during the day from the e-diary. Scores range from 1 (none) to 5 (a very great deal). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Change From Baseline in Daytime Experiences of Shortness of Breath | Week 24 (N=121, 130, 133) | -0.134 Units on a scale | Standard Error 0.039 |
| Placebo Respimat | Change From Baseline in Daytime Experiences of Shortness of Breath | Week 48 (N=119, 123, 125) | -0.219 Units on a scale | Standard Error 0.039 |
| Tio R2.5 | Change From Baseline in Daytime Experiences of Shortness of Breath | Week 24 (N=121, 130, 133) | -0.178 Units on a scale | Standard Error 0.038 |
| Tio R2.5 | Change From Baseline in Daytime Experiences of Shortness of Breath | Week 48 (N=119, 123, 125) | -0.231 Units on a scale | Standard Error 0.038 |
| Tio R5 | Change From Baseline in Daytime Experiences of Shortness of Breath | Week 24 (N=121, 130, 133) | -0.240 Units on a scale | Standard Error 0.038 |
| Tio R5 | Change From Baseline in Daytime Experiences of Shortness of Breath | Week 48 (N=119, 123, 125) | -0.253 Units on a scale | Standard Error 0.038 |
Comparison: Week 24p-value: 0.349895% CI: [-0.135, 0.048]Mixed Models Analysis
Comparison: Week 24p-value: 0.022295% CI: [-0.196, -0.015]Mixed Models Analysis
Comparison: Week 48p-value: 0.79995% CI: [-0.104, 0.08]Mixed Models Analysis
Comparison: Week 48p-value: 0.458695% CI: [-0.126, 0.057]Mixed Models Analysis
Secondary
Change From Baseline in Daytime Experiences of Wheeze or Cough
Change from baseline in daytime experiences of wheeze or cough based on the weekly mean at weeks 24 and 48. Daytime experiences of wheeze or cough was assessed by the question did you experience wheeze or cough during the day? from the e-diary. Scores range from 1 (not at all) to 5 (all the time). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Change From Baseline in Daytime Experiences of Wheeze or Cough | Week 24 (N=121, 130, 133) | -0.261 Units on a scale | Standard Error 0.046 |
| Placebo Respimat | Change From Baseline in Daytime Experiences of Wheeze or Cough | Week 48 (N=119, 123, 125) | -0.340 Units on a scale | Standard Error 0.047 |
| Tio R2.5 | Change From Baseline in Daytime Experiences of Wheeze or Cough | Week 24 (N=121, 130, 133) | -0.307 Units on a scale | Standard Error 0.045 |
| Tio R2.5 | Change From Baseline in Daytime Experiences of Wheeze or Cough | Week 48 (N=119, 123, 125) | -0.337 Units on a scale | Standard Error 0.045 |
| Tio R5 | Change From Baseline in Daytime Experiences of Wheeze or Cough | Week 24 (N=121, 130, 133) | -0.355 Units on a scale | Standard Error 0.045 |
| Tio R5 | Change From Baseline in Daytime Experiences of Wheeze or Cough | Week 48 (N=119, 123, 125) | -0.393 Units on a scale | Standard Error 0.046 |
Comparison: Week 24p-value: 0.422195% CI: [-0.156, 0.065]Mixed Models Analysis
Comparison: Week 24p-value: 0.095995% CI: [-0.204, 0.017]Mixed Models Analysis
Comparison: Week 48p-value: 0.962795% CI: [-0.109, 0.114]Mixed Models Analysis
Comparison: Week 48p-value: 0.345795% CI: [-0.165, 0.058]Mixed Models Analysis
Secondary
Change From Baseline in Morning Asthma Symptoms
Change from baseline in morning asthma symptoms based on the weekly mean at weeks 24 and 48. Morning asthma symptoms was assessed by the question how were your asthma symptoms this morning? from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Change From Baseline in Morning Asthma Symptoms | Week 24 (N=122, 130, 130) | -0.138 Units on a scale | Standard Error 0.039 |
| Placebo Respimat | Change From Baseline in Morning Asthma Symptoms | Week 48 (N=119, 122, 125) | -0.177 Units on a scale | Standard Error 0.039 |
| Tio R2.5 | Change From Baseline in Morning Asthma Symptoms | Week 24 (N=122, 130, 130) | -0.138 Units on a scale | Standard Error 0.038 |
| Tio R2.5 | Change From Baseline in Morning Asthma Symptoms | Week 48 (N=119, 122, 125) | -0.230 Units on a scale | Standard Error 0.038 |
| Tio R5 | Change From Baseline in Morning Asthma Symptoms | Week 24 (N=122, 130, 130) | -0.220 Units on a scale | Standard Error 0.038 |
| Tio R5 | Change From Baseline in Morning Asthma Symptoms | Week 48 (N=119, 122, 125) | -0.221 Units on a scale | Standard Error 0.038 |
Comparison: Week 24p-value: 0.98895% CI: [-0.091, 0.092]Mixed Models Analysis
Comparison: Week 24p-value: 0.079495% CI: [-0.173, 0.01]Mixed Models Analysis
Comparison: Week 48p-value: 0.262395% CI: [-0.145, 0.04]Mixed Models Analysis
Comparison: Week 48p-value: 0.355295% CI: [-0.136, 0.04]Mixed Models Analysis
Secondary
Change From Baseline in Nighttime Awakenings
Change from baseline in nighttime awakenings based on the weekly mean at weeks 24 and 48. Nighttime awakenings was assessed by the question Did you wake up during the night due to your asthma? from the e-diary. Scores range from 1 (did not wake up) to 5 (was awake all night). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Change From Baseline in Nighttime Awakenings | Week 24 (N=122, 130, 130) | -0.070 Units on a scale | Standard Error 0.03 |
| Placebo Respimat | Change From Baseline in Nighttime Awakenings | Week 48 (N=119, 122, 125) | -0.101 Units on a scale | Standard Error 0.03 |
| Tio R2.5 | Change From Baseline in Nighttime Awakenings | Week 24 (N=122, 130, 130) | -0.079 Units on a scale | Standard Error 0.029 |
| Tio R2.5 | Change From Baseline in Nighttime Awakenings | Week 48 (N=119, 122, 125) | -0.131 Units on a scale | Standard Error 0.029 |
| Tio R5 | Change From Baseline in Nighttime Awakenings | Week 24 (N=122, 130, 130) | -0.144 Units on a scale | Standard Error 0.029 |
| Tio R5 | Change From Baseline in Nighttime Awakenings | Week 48 (N=119, 122, 125) | -0.127 Units on a scale | Standard Error 0.029 |
Comparison: Week 24p-value: 0.793195% CI: [-0.08, 0.061]Mixed Models Analysis
Comparison: Week 24p-value: 0.036995% CI: [-0.145, -0.005]Mixed Models Analysis
Comparison: Week 48p-value: 0.408695% CI: [-0.101, 0.041]Mixed Models Analysis
Comparison: Week 48p-value: 0.471495% CI: [-0.097, 0.045]Mixed Models Analysis
Secondary
FEV1 a.m Change From Baseline
Change from baseline in morning (a.m.) FEV1 based on the weekly mean at week 24 and 48. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | FEV1 a.m Change From Baseline | Week 24 (N=122, 130, 130) | 0.191 Litres | Standard Error 0.041 |
| Placebo Respimat | FEV1 a.m Change From Baseline | Week 48 (N=119, 122, 125) | 0.236 Litres | Standard Error 0.041 |
| Tio R2.5 | FEV1 a.m Change From Baseline | Week 24 (N=122, 130, 130) | 0.209 Litres | Standard Error 0.039 |
| Tio R2.5 | FEV1 a.m Change From Baseline | Week 48 (N=119, 122, 125) | 0.259 Litres | Standard Error 0.04 |
| Tio R5 | FEV1 a.m Change From Baseline | Week 24 (N=122, 130, 130) | 0.126 Litres | Standard Error 0.039 |
| Tio R5 | FEV1 a.m Change From Baseline | Week 48 (N=119, 122, 125) | 0.221 Litres | Standard Error 0.04 |
Comparison: Week 24p-value: 0.693295% CI: [-0.075, 0.113]Mixed Models Analysis
Comparison: Week 24p-value: 0.174195% CI: [-0.158, 0.029]Mixed Models Analysis
Comparison: Week 48p-value: 0.62595% CI: [-0.071, 0.118]Mixed Models Analysis
Comparison: Week 48p-value: 0.759795% CI: [-0.109, 0.08]Mixed Models Analysis
Secondary
FEV1 AUC (0-3h) Change From Baseline
Change from baseline of area under the curve (AUC) from 0 to 3 hours 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). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Time frame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at week 24
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | FEV1 AUC (0-3h) Change From Baseline | 0.152 Litres (L) | Standard Error 0.026 |
| Tio R2.5 | FEV1 AUC (0-3h) Change From Baseline | 0.306 Litres (L) | Standard Error 0.025 |
| Tio R5 | FEV1 AUC (0-3h) Change From Baseline | 0.309 Litres (L) | Standard Error 0.025 |
Comparison: Week 24p-value: <0.000195% CI: [0.095, 0.212]Mixed Models Analysis
Comparison: Week 24p-value: <0.000195% CI: [0.098, 0.215]Mixed Models Analysis
Secondary
FEV1 Change From Baseline at Each Individual Timepoint
FEV1 change from baseline to week 24 at each individual timepoint. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | FEV1 Change From Baseline at Each Individual Timepoint | 2 hours post-dose (Week 24) (N=126, 131, 134) | 0.144 Litres (L) | Standard Error 0.028 |
| Placebo Respimat | FEV1 Change From Baseline at Each Individual Timepoint | 1 hour post-dose (Week 24) (N=126, 131, 134) | 0.165 Litres (L) | Standard Error 0.028 |
| Placebo Respimat | FEV1 Change From Baseline at Each Individual Timepoint | 10 minutes pre-dose (Week 24) (N=126, 131, 134) | 0.156 Litres (L) | Standard Error 0.031 |
| Placebo Respimat | FEV1 Change From Baseline at Each Individual Timepoint | 30 minutes post-dose (Week 24) (N=126, 131, 134) | 0.156 Litres (L) | Standard Error 0.027 |
| Placebo Respimat | FEV1 Change From Baseline at Each Individual Timepoint | 3 hours post-dose (Week 24) (N=126, 131, 134) | 0.147 Litres (L) | Standard Error 0.027 |
| Tio R2.5 | FEV1 Change From Baseline at Each Individual Timepoint | 1 hour post-dose (Week 24) (N=126, 131, 134) | 0.313 Litres (L) | Standard Error 0.027 |
| Tio R2.5 | FEV1 Change From Baseline at Each Individual Timepoint | 10 minutes pre-dose (Week 24) (N=126, 131, 134) | 0.272 Litres (L) | Standard Error 0.03 |
| Tio R2.5 | FEV1 Change From Baseline at Each Individual Timepoint | 30 minutes post-dose (Week 24) (N=126, 131, 134) | 0.295 Litres (L) | Standard Error 0.026 |
| Tio R2.5 | FEV1 Change From Baseline at Each Individual Timepoint | 2 hours post-dose (Week 24) (N=126, 131, 134) | 0.307 Litres (L) | Standard Error 0.027 |
| Tio R2.5 | FEV1 Change From Baseline at Each Individual Timepoint | 3 hours post-dose (Week 24) (N=126, 131, 134) | 0.325 Litres (L) | Standard Error 0.026 |
| Tio R5 | FEV1 Change From Baseline at Each Individual Timepoint | 3 hours post-dose (Week 24) (N=126, 131, 134) | 0.322 Litres (L) | Standard Error 0.026 |
| Tio R5 | FEV1 Change From Baseline at Each Individual Timepoint | 2 hours post-dose (Week 24) (N=126, 131, 134) | 0.312 Litres (L) | Standard Error 0.027 |
| Tio R5 | FEV1 Change From Baseline at Each Individual Timepoint | 10 minutes pre-dose (Week 24) (N=126, 131, 134) | 0.274 Litres (L) | Standard Error 0.03 |
| Tio R5 | FEV1 Change From Baseline at Each Individual Timepoint | 1 hour post-dose (Week 24) (N=126, 131, 134) | 0.312 Litres (L) | Standard Error 0.027 |
| Tio R5 | FEV1 Change From Baseline at Each Individual Timepoint | 30 minutes post-dose (Week 24) (N=126, 131, 134) | 0.307 Litres (L) | Standard Error 0.027 |
Comparison: 10 minutes pre-dose (Week 24)p-value: 0.001295% CI: [0.046, 0.186]Mixed Models Analysis
Comparison: 10 minutes pre-dose (Week 24)p-value: 0.00195% CI: [0.048, 0.188]Mixed Models Analysis
Comparison: 30 minutes post-dose (Week 24)p-value: <0.000195% CI: [0.076, 0.201]Mixed Models Analysis
Comparison: 30 minutes post-dose (Week 24)p-value: <0.000195% CI: [0.088, 0.213]Mixed Models Analysis
Comparison: 1 hour post-dose (Week 24)p-value: <0.000195% CI: [0.084, 0.211]Mixed Models Analysis
Comparison: 1 hour post-dose (Week 24)p-value: <0.000195% CI: [0.084, 0.21]Mixed Models Analysis
Comparison: 2 hours post-dose (Week 24)p-value: <0.000195% CI: [0.101, 0.226]Mixed Models Analysis
Comparison: 2 hours post-dose (Week 24)p-value: <0.000195% CI: [0.106, 0.231]Mixed Models Analysis
Comparison: 3 hours post-dose (Week 24)p-value: <0.000195% CI: [0.116, 0.24]Mixed Models Analysis
Comparison: 3 hours post-dose (Week 24)p-value: <0.000195% CI: [0.114, 0.238]Mixed Models Analysis
Secondary
FEV1 Peak (0-3h) at Week 48 Change From Baseline
Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Time frame: Baseline and Week 48.
Population: FAS. Missing data at a visit was imputed by available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | FEV1 Peak (0-3h) at Week 48 Change From Baseline | 0.351 Litres (L) | Standard Error 0.027 |
| Tio R2.5 | FEV1 Peak (0-3h) at Week 48 Change From Baseline | 0.474 Litres (L) | Standard Error 0.026 |
| Tio R5 | FEV1 Peak (0-3h) at Week 48 Change From Baseline | 0.477 Litres (L) | Standard Error 0.026 |
p-value: <0.000195% CI: [0.062, 0.185]Mixed Models Analysis
p-value: <0.000195% CI: [0.065, 0.188]Mixed Models Analysis
Secondary
FEV1 p.m. Change From Baseline
Change from baseline in evening (p.m.) FEV1 based on the weekly mean at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | FEV1 p.m. Change From Baseline | Week 24 (N=121, 129, 128) | 0.167 Litres (L) | Standard Error 0.042 |
| Placebo Respimat | FEV1 p.m. Change From Baseline | Week 48 (N=119, 123, 125) | 0.202 Litres (L) | Standard Error 0.042 |
| Tio R2.5 | FEV1 p.m. Change From Baseline | Week 24 (N=121, 129, 128) | 0.142 Litres (L) | Standard Error 0.041 |
| Tio R2.5 | FEV1 p.m. Change From Baseline | Week 48 (N=119, 123, 125) | 0.208 Litres (L) | Standard Error 0.041 |
| Tio R5 | FEV1 p.m. Change From Baseline | Week 24 (N=121, 129, 128) | 0.092 Litres (L) | Standard Error 0.041 |
| Tio R5 | FEV1 p.m. Change From Baseline | Week 48 (N=119, 123, 125) | 0.159 Litres (L) | Standard Error 0.041 |
Comparison: Week 24p-value: 0.616695% CI: [-0.122, 0.073]Mixed Models Analysis
Comparison: Week 24p-value: 0.126795% CI: [-0.173, 0.021]Mixed Models Analysis
Comparison: Week 48p-value: 0.995% CI: [-0.092, 0.105]Mixed Models Analysis
Comparison: Week 48p-value: 0.389795% CI: [-0.141, 0.055]Mixed Models Analysis
Secondary
FVC AUC (0-3h) Change From Baseline
Change from baseline of area under the curve (AUC) from 0 to 3 hours for FVC (Forced vital capacity) (FVC AUC (0-3h)) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Time frame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Respimat | FVC AUC (0-3h) Change From Baseline | 0.130 Litres (L) | Standard Error 0.03 |
| Tio R2.5 | FVC AUC (0-3h) Change From Baseline | 0.235 Litres (L) | Standard Error 0.029 |
| Tio R5 | FVC AUC (0-3h) Change From Baseline | 0.207 Litres (L) | Standard Error 0.029 |
Comparison: Week 24p-value: 0.002395% CI: [0.037, 0.172]Mixed Models Analysis
Comparison: Week 24p-value: 0.025595% CI: [0.009, 0.143]Mixed Models Analysis
Secondary
FVC Change From Baseline at Each Individual Timepoint
FVC change from baseline to week 24 at each individual timepoint. The measured values presented are actually adjusted means The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at Week 24
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | FVC Change From Baseline at Each Individual Timepoint | 2 hours post-dose (Week 24) (N=124, 131, 134) | 0.117 Litres (L) | Standard Error 0.033 |
| Placebo Respimat | FVC Change From Baseline at Each Individual Timepoint | 1 hour post-dose (Week 24) (N=124, 131, 134) | 0.142 Litres (L) | Standard Error 0.032 |
| Placebo Respimat | FVC Change From Baseline at Each Individual Timepoint | 10 minutes pre-dose (Week 24) (N=124, 131, 134) | 0.154 Litres (L) | Standard Error 0.035 |
| Placebo Respimat | FVC Change From Baseline at Each Individual Timepoint | 30 minutes post-dose (Week 24) (N=124, 131, 134) | 0.144 Litres (L) | Standard Error 0.032 |
| Placebo Respimat | FVC Change From Baseline at Each Individual Timepoint | 3 hours post-dose (Week 24) (N=124, 131, 134) | 0.118 Litres (L) | Standard Error 0.033 |
| Tio R2.5 | FVC Change From Baseline at Each Individual Timepoint | 1 hour post-dose (Week 24) (N=124, 131, 134) | 0.252 Litres (L) | Standard Error 0.031 |
| Tio R2.5 | FVC Change From Baseline at Each Individual Timepoint | 10 minutes pre-dose (Week 24) (N=124, 131, 134) | 0.246 Litres (L) | Standard Error 0.034 |
| Tio R2.5 | FVC Change From Baseline at Each Individual Timepoint | 30 minutes post-dose (Week 24) (N=124, 131, 134) | 0.222 Litres (L) | Standard Error 0.031 |
| Tio R2.5 | FVC Change From Baseline at Each Individual Timepoint | 2 hours post-dose (Week 24) (N=124, 131, 134) | 0.230 Litres (L) | Standard Error 0.031 |
| Tio R2.5 | FVC Change From Baseline at Each Individual Timepoint | 3 hours post-dose (Week 24) (N=124, 131, 134) | 0.233 Litres (L) | Standard Error 0.032 |
| Tio R5 | FVC Change From Baseline at Each Individual Timepoint | 3 hours post-dose (Week 24) (N=124, 131, 134) | 0.210 Litres (L) | Standard Error 0.032 |
| Tio R5 | FVC Change From Baseline at Each Individual Timepoint | 2 hours post-dose (Week 24) (N=124, 131, 134) | 0.210 Litres (L) | Standard Error 0.032 |
| Tio R5 | FVC Change From Baseline at Each Individual Timepoint | 10 minutes pre-dose (Week 24) (N=124, 131, 134) | 0.206 Litres (L) | Standard Error 0.034 |
| Tio R5 | FVC Change From Baseline at Each Individual Timepoint | 1 hour post-dose (Week 24) (N=124, 131, 134) | 0.202 Litres (L) | Standard Error 0.031 |
| Tio R5 | FVC Change From Baseline at Each Individual Timepoint | 30 minutes post-dose (Week 24) (N=124, 131, 134) | 0.211 Litres (L) | Standard Error 0.031 |
Comparison: 30 minutes post-dose (Week 24)p-value: 0.034495% CI: [0.006, 0.15]Mixed Models Analysis
Comparison: 30 minutes post-dose (Week 24)p-value: 0.069695% CI: [-0.005, 0.139]Mixed Models Analysis
Comparison: 10 minutes pre-dose (Week 24)p-value: 0.022895% CI: [0.013, 0.171]Mixed Models Analysis
Comparison: 10 minutes pre-dose.(Week 24)p-value: 0.19895% CI: [-0.027, 0.131]Mixed Models Analysis
Comparison: 1 hour post-dose (week 24)p-value: 0.003295% CI: [0.037, 0.182]Mixed Models Analysis
Comparison: 1 hour post-dose (week 24)p-value: 0.104495% CI: [-0.012, 0.132]Mixed Models Analysis
Comparison: 2 hours post-dose (week 24)p-value: 0.002795% CI: [0.039, 0.186]Mixed Models Analysis
Comparison: 2 hours post-dose (week 24)p-value: 0.01395% CI: [0.02, 0.166]Mixed Models Analysis
Comparison: 3 hours post-dose (week 24)p-value: 0.002595% CI: [0.041, 0.19]Mixed Models Analysis
Comparison: 3 hours post-dose (Week 24)p-value: 0.015695% CI: [0.017, 0.166]Mixed Models Analysis
Secondary
FVC Peak(0-3h) Change From Baseline
Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak(0-3h)) after 24 and 48 Weeks of treatment. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | FVC Peak(0-3h) Change From Baseline | Week 24 (N=124, 130, 134) | 0.215 Litres (L) | Standard Error 0.033 |
| Placebo Respimat | FVC Peak(0-3h) Change From Baseline | Week 48 (N=124, 130, 130) | 0.361 Litres (L) | Standard Error 0.033 |
| Tio R2.5 | FVC Peak(0-3h) Change From Baseline | Week 24 (N=124, 130, 134) | 0.325 Litres (L) | Standard Error 0.032 |
| Tio R2.5 | FVC Peak(0-3h) Change From Baseline | Week 48 (N=124, 130, 130) | 0.430 Litres (L) | Standard Error 0.032 |
| Tio R5 | FVC Peak(0-3h) Change From Baseline | Week 24 (N=124, 130, 134) | 0.307 Litres (L) | Standard Error 0.032 |
| Tio R5 | FVC Peak(0-3h) Change From Baseline | Week 48 (N=124, 130, 130) | 0.413 Litres (L) | Standard Error 0.032 |
Comparison: Week 24p-value: 0.003695% CI: [0.036, 0.184]Mixed Models Analysis
Comparison: Week 24p-value: 0.015295% CI: [0.018, 0.165]Mixed Models Analysis
Comparison: Week 48p-value: 0.068795% CI: [-0.005, 0.143]Mixed Models Analysis
Comparison: Week 48p-value: 0.166695% CI: [-0.022, 0.126]Mixed Models Analysis
Secondary
PAQLQ(S) Activity Limitation Domain Score
PAQLQ(S) activity limitation domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Weeks 24 and 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | PAQLQ(S) Activity Limitation Domain Score | Week 24 (N= 126, 131, 134) | 5.898 Units on a Scale | Standard Error 0.069 |
| Placebo Respimat | PAQLQ(S) Activity Limitation Domain Score | Week 48 (N=124, 130, 130) | 6.249 Units on a Scale | Standard Error 0.07 |
| Tio R2.5 | PAQLQ(S) Activity Limitation Domain Score | Week 24 (N= 126, 131, 134) | 6.089 Units on a Scale | Standard Error 0.067 |
| Tio R2.5 | PAQLQ(S) Activity Limitation Domain Score | Week 48 (N=124, 130, 130) | 6.284 Units on a Scale | Standard Error 0.068 |
| Tio R5 | PAQLQ(S) Activity Limitation Domain Score | Week 24 (N= 126, 131, 134) | 6.023 Units on a Scale | Standard Error 0.067 |
| Tio R5 | PAQLQ(S) Activity Limitation Domain Score | Week 48 (N=124, 130, 130) | 6.319 Units on a Scale | Standard Error 0.067 |
Comparison: Week 24p-value: 0.013995% CI: [0.039, 0.343]Mixed Models Analysis
Comparison: Week 24p-value: 0.104395% CI: [-0.026, 0.276]Mixed Models Analysis
Comparison: Week 48p-value: 0.654795% CI: [-0.118, 0.187]Mixed Models Analysis
Comparison: Week 48p-value: 0.364895% CI: [-0.082, 0.222]Mixed Models Analysis
Secondary
PAQLQ(S) Emotional Function Domain Score
PAQLQ(S) emotional function domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Weeks 24 and 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | PAQLQ(S) Emotional Function Domain Score | Week 24 (N=126, 131, 134) | 6.157 Units on a Scale | Standard Error 0.067 |
| Placebo Respimat | PAQLQ(S) Emotional Function Domain Score | Week 48 (N=124, 130, 130) | 6.481 Units on a Scale | Standard Error 0.067 |
| Tio R2.5 | PAQLQ(S) Emotional Function Domain Score | Week 24 (N=126, 131, 134) | 6.323 Units on a Scale | Standard Error 0.065 |
| Tio R2.5 | PAQLQ(S) Emotional Function Domain Score | Week 48 (N=124, 130, 130) | 6.420 Units on a Scale | Standard Error 0.065 |
| Tio R5 | PAQLQ(S) Emotional Function Domain Score | Week 24 (N=126, 131, 134) | 6.298 Units on a Scale | Standard Error 0.064 |
| Tio R5 | PAQLQ(S) Emotional Function Domain Score | Week 48 (N=124, 130, 130) | 6.491 Units on a Scale | Standard Error 0.065 |
Comparison: Week 24p-value: 0.025695% CI: [0.02, 0.312]Mixed Models Analysis
Comparison: Week 24p-value: 0.056195% CI: [-0.004, 0.286]Mixed Models Analysis
Comparison: Week 48p-value: 0.412795% CI: [-0.208, 0.085]Mixed Models Analysis
Comparison: Week 48p-value: 0.892295% CI: [-0.136, 0.156]Mixed Models Analysis
Secondary
PAQLQ(S) Symptom Domain Score
PAQLQ(S) symptom domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score was calculated as the mean of the items in the domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Weeks 24 and 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | PAQLQ(S) Symptom Domain Score | Week 24 (N=126, 131, 134) | 5.840 Units on a Scale | Standard Error 0.076 |
| Placebo Respimat | PAQLQ(S) Symptom Domain Score | Week 48 (N=124, 130, 130) | 6.195 Units on a Scale | Standard Error 0.076 |
| Tio R2.5 | PAQLQ(S) Symptom Domain Score | Week 48 (N=124, 130, 130) | 6.177 Units on a Scale | Standard Error 0.074 |
| Tio R2.5 | PAQLQ(S) Symptom Domain Score | Week 24 (N=126, 131, 134) | 6.015 Units on a Scale | Standard Error 0.074 |
| Tio R5 | PAQLQ(S) Symptom Domain Score | Week 24 (N=126, 131, 134) | 5.967 Units on a Scale | Standard Error 0.073 |
| Tio R5 | PAQLQ(S) Symptom Domain Score | Week 48 (N=124, 130, 130) | 6.199 Units on a Scale | Standard Error 0.074 |
Comparison: Week 24p-value: 0.039295% CI: [0.009, 0.341]Mixed Models Analysis
Comparison: Week 24p-value: 0.135195% CI: [-0.039, 0.292]Mixed Models Analysis
Comparison: Week 48p-value: 0.829195% CI: [-0.185, 0.149]Mixed Models Analysis
Comparison: Week 48p-value: 0.965595% CI: [-0.163, 0.171]Mixed Models Analysis
Secondary
PAQLQ(S) Total Score
Standardised Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S)) total score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). Total Score is calculated as mean of all 23 questions. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Weeks 24 and 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | PAQLQ(S) Total Score | Week 24 (N= 126, 131, 134) | 5.966 Units on a Scale | Standard Error 0.065 |
| Placebo Respimat | PAQLQ(S) Total Score | Week 48 (N=124, 130, 130) | 6.309 Units on a Scale | Standard Error 0.065 |
| Tio R2.5 | PAQLQ(S) Total Score | Week 24 (N= 126, 131, 134) | 6.142 Units on a Scale | Standard Error 0.063 |
| Tio R2.5 | PAQLQ(S) Total Score | Week 48 (N=124, 130, 130) | 6.288 Units on a Scale | Standard Error 0.063 |
| Tio R5 | PAQLQ(S) Total Score | Week 24 (N= 126, 131, 134) | 6.093 Units on a Scale | Standard Error 0.062 |
| Tio R5 | PAQLQ(S) Total Score | Week 48 (N=124, 130, 130) | 6.327 Units on a Scale | Standard Error 0.063 |
Comparison: Week 24p-value: 0.014495% CI: [0.035, 0.316]Mixed Models Analysis
Comparison: Week 24p-value: 0.074795% CI: [-0.013, 0.267]Mixed Models Analysis
Comparison: Week 48p-value: 0.765495% CI: [-0.163, 0.12]Mixed Models Analysis
Comparison: Week 48p-value: 0.808295% CI: [-0.124, 0.158]Mixed Models Analysis
Secondary
Peak Expiratory Flow (PEF) a.m. Change From Baseline
Change from baseline in the morning (a.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Peak Expiratory Flow (PEF) a.m. Change From Baseline | Week 24 (N=122, 130, 130) | 14.153 Litres per min (L/min) | Standard Error 4.556 |
| Placebo Respimat | Peak Expiratory Flow (PEF) a.m. Change From Baseline | Week 48 (N=119, 122, 125) | 20.824 Litres per min (L/min) | Standard Error 4.581 |
| Tio R2.5 | Peak Expiratory Flow (PEF) a.m. Change From Baseline | Week 24 (N=122, 130, 130) | 22.660 Litres per min (L/min) | Standard Error 4.406 |
| Tio R2.5 | Peak Expiratory Flow (PEF) a.m. Change From Baseline | Week 48 (N=119, 122, 125) | 26.362 Litres per min (L/min) | Standard Error 4.44 |
| Tio R5 | Peak Expiratory Flow (PEF) a.m. Change From Baseline | Week 24 (N=122, 130, 130) | 21.646 Litres per min (L/min) | Standard Error 4.434 |
| Tio R5 | Peak Expiratory Flow (PEF) a.m. Change From Baseline | Week 48 (N=119, 122, 125) | 29.598 Litres per min (L/min) | Standard Error 4.466 |
Comparison: Week 24p-value: 0.114695% CI: [-2.063, 19.077]Mixed Models Analysis
Comparison: Week 24p-value: 0.162895% CI: [-3.034, 18.02]Mixed Models Analysis
Comparison: Week 48p-value: 0.308595% CI: [-5.127, 16.203]Mixed Models Analysis
Comparison: Week 48p-value: 0.105395% CI: [-1.847, 19.394]Mixed Models Analysis
Secondary
PEF p.m. Change From Baseline
Change from baseline in the evening (p.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | PEF p.m. Change From Baseline | Week 24 (N= 121, 130, 133) | 3.179 Litres per min (L/min) | Standard Error 4.597 |
| Placebo Respimat | PEF p.m. Change From Baseline | Week 48 (N=119, 123, 125) | 17.100 Litres per min (L/min) | Standard Error 4.622 |
| Tio R2.5 | PEF p.m. Change From Baseline | Week 24 (N= 121, 130, 133) | 15.539 Litres per min (L/min) | Standard Error 4.444 |
| Tio R2.5 | PEF p.m. Change From Baseline | Week 48 (N=119, 123, 125) | 15.219 Litres per min (L/min) | Standard Error 4.475 |
| Tio R5 | PEF p.m. Change From Baseline | Week 24 (N= 121, 130, 133) | 17.325 Litres per min (L/min) | Standard Error 4.464 |
| Tio R5 | PEF p.m. Change From Baseline | Week 48 (N=119, 123, 125) | 21.276 Litres per min (L/min) | Standard Error 4.504 |
Comparison: Week 24p-value: 0.023695% CI: [1.663, 23.056]Mixed Models Analysis
Comparison: Week 24p-value: 0.009395% CI: [3.497, 24.794]Mixed Models Analysis
Comparison: Week 48p-value: 0.732295% CI: [-12.667, 8.904]Mixed Models Analysis
Comparison: Week 48p-value: 0.446395% CI: [-6.578, 14.929]Mixed Models Analysis
Secondary
PEF Variability Change From Baseline
Change from baseline in the peak expiratory flow variability based on the weekly mean at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | PEF Variability Change From Baseline | Week 24 (N=121, 129, 128) | -1.204 Percentage of PEF | Standard Error 0.826 |
| Placebo Respimat | PEF Variability Change From Baseline | Week 48 (N=117, 120, 121) | -0.320 Percentage of PEF | Standard Error 0.835 |
| Tio R2.5 | PEF Variability Change From Baseline | Week 24 (N=121, 129, 128) | -0.942 Percentage of PEF | Standard Error 0.798 |
| Tio R2.5 | PEF Variability Change From Baseline | Week 48 (N=117, 120, 121) | -0.048 Percentage of PEF | Standard Error 0.814 |
| Tio R5 | PEF Variability Change From Baseline | Week 24 (N=121, 129, 128) | -1.038 Percentage of PEF | Standard Error 0.803 |
| Tio R5 | PEF Variability Change From Baseline | Week 48 (N=117, 120, 121) | -0.899 Percentage of PEF | Standard Error 0.818 |
Comparison: Week 24p-value: 0.800895% CI: [-1.775, 2.299]Mixed Models Analysis
Comparison: Week 24p-value: 0.873195% CI: [-1.875, 2.208]Mixed Models Analysis
Comparison: Week 48p-value: 0.797595% CI: [-1.803, 2.346]Mixed Models Analysis
Comparison: Week 48p-value: 0.584595% CI: [-2.656, 1.498]Mixed Models Analysis
Secondary
Responders in PAQLQ(S) at Weeks 24 and 48
Responders in PAQLQ(S) at weeks 24 and 48. 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). No statistical testing was performed for PAQLQ(S) total score responders. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control).
Time frame: Weeks 24 and 48.
Population: FAS, missing data for patients not withdrawn from the study were either categorised as no change or based on available data, withdrawn patients were imputed based upon discontinuation reason.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Respimat | Responders in PAQLQ(S) at Weeks 24 and 48 | Responders at Week 24 | 67 Patients |
| Placebo Respimat | Responders in PAQLQ(S) at Weeks 24 and 48 | No Change at Week 24 | 58 Patients |
| Placebo Respimat | Responders in PAQLQ(S) at Weeks 24 and 48 | Worsening at Week 24 | 6 Patients |
| Placebo Respimat | Responders in PAQLQ(S) at Weeks 24 and 48 | Responders at Week 48 | 89 Patients |
| Placebo Respimat | Responders in PAQLQ(S) at Weeks 24 and 48 | No Change at Week 48 | 39 Patients |
| Placebo Respimat | Responders in PAQLQ(S) at Weeks 24 and 48 | Worsening at Week 48 | 3 Patients |
| Tio R2.5 | Responders in PAQLQ(S) at Weeks 24 and 48 | Worsening at Week 48 | 6 Patients |
| Tio R2.5 | Responders in PAQLQ(S) at Weeks 24 and 48 | Responders at Week 24 | 82 Patients |
| Tio R2.5 | Responders in PAQLQ(S) at Weeks 24 and 48 | Responders at Week 48 | 96 Patients |
| Tio R2.5 | Responders in PAQLQ(S) at Weeks 24 and 48 | No Change at Week 48 | 33 Patients |
| Tio R2.5 | Responders in PAQLQ(S) at Weeks 24 and 48 | No Change at Week 24 | 47 Patients |
| Tio R2.5 | Responders in PAQLQ(S) at Weeks 24 and 48 | Worsening at Week 24 | 6 Patients |
| Tio R5 | Responders in PAQLQ(S) at Weeks 24 and 48 | No Change at Week 24 | 56 Patients |
| Tio R5 | Responders in PAQLQ(S) at Weeks 24 and 48 | Worsening at Week 24 | 6 Patients |
| Tio R5 | Responders in PAQLQ(S) at Weeks 24 and 48 | Worsening at Week 48 | 1 Patients |
| Tio R5 | Responders in PAQLQ(S) at Weeks 24 and 48 | Responders at Week 48 | 92 Patients |
| Tio R5 | Responders in PAQLQ(S) at Weeks 24 and 48 | Responders at Week 24 | 73 Patients |
| Tio R5 | Responders in PAQLQ(S) at Weeks 24 and 48 | No Change at Week 48 | 42 Patients |
Secondary
Trough FEV1 Change From Baseline
Change from Baseline in Trough (pre-dose) Forced Expiratory Volume (FEV) in 1 second (FEV1) measured at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: Full Analysis Set (FAS) was equal to treated set which included all randomised patients who received at least 1 documented dose of study medication. Missing data at a visit was imputed by available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Trough FEV1 Change From Baseline | Week 24 (N=126, 131, 134) | 0.156 Litres (L) | Standard Error 0.031 |
| Placebo Respimat | Trough FEV1 Change From Baseline | Week 48 (N=124, 130, 130) | 0.266 Litres (L) | Standard Error 0.032 |
| Tio R2.5 | Trough FEV1 Change From Baseline | Week 24 (N=126, 131, 134) | 0.272 Litres (L) | Standard Error 0.03 |
| Tio R2.5 | Trough FEV1 Change From Baseline | Week 48 (N=124, 130, 130) | 0.337 Litres (L) | Standard Error 0.03 |
| Tio R5 | Trough FEV1 Change From Baseline | Week 24 (N=126, 131, 134) | 0.274 Litres (L) | Standard Error 0.03 |
| Tio R5 | Trough FEV1 Change From Baseline | Week 48 (N=124, 130, 130) | 0.365 Litres (L) | Standard Error 0.031 |
Comparison: Week 24p-value: 0.001295% CI: [0.046, 0.186]Mixed Models Analysis
Comparison: Week 24p-value: 0.00195% CI: [0.048, 0.188]Mixed Models Analysis
Comparison: Week 48p-value: 0.047795% CI: [0.001, 0.142]Mixed Models Analysis
Comparison: Week 48p-value: 0.005995% CI: [0.029, 0.17]Mixed Models Analysis
Secondary
Trough FVC Change From Baseline
Change from baseline in Trough (pre-dose) FVC measured at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Trough FVC Change From Baseline | Week 24 (N=126, 131, 134) | 0.154 Litres (L) | Standard Error 0.035 |
| Placebo Respimat | Trough FVC Change From Baseline | Week 48 (N=124, 130, 130) | 0.280 Litres (L) | Standard Error 0.035 |
| Tio R2.5 | Trough FVC Change From Baseline | Week 24 (N=126, 131, 134) | 0.246 Litres (L) | Standard Error 0.034 |
| Tio R2.5 | Trough FVC Change From Baseline | Week 48 (N=124, 130, 130) | 0.341 Litres (L) | Standard Error 0.034 |
| Tio R5 | Trough FVC Change From Baseline | Week 24 (N=126, 131, 134) | 0.206 Litres (L) | Standard Error 0.034 |
| Tio R5 | Trough FVC Change From Baseline | Week 48 (N=124, 130, 130) | 0.333 Litres (L) | Standard Error 0.034 |
Comparison: Week 24p-value: 0.022895% CI: [0.013, 0.171]Mixed Models Analysis
Comparison: Week 24p-value: 0.19895% CI: [-0.027, 0.131]Mixed Models Analysis
Comparison: Week 48p-value: 0.125695% CI: [-0.017, 0.141]Mixed Models Analysis
Comparison: Week 48p-value: 0.18895% CI: [-0.026, 0.133]Mixed Models Analysis
Secondary
Use of PRN (Pro re Nata) Rescue Medication Per Day
Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used per day (24 hour period) based on the weekly mean at weeks 24 and 48. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Use of PRN (Pro re Nata) Rescue Medication Per Day | Week 24 (N=122, 130, 133) | -0.437 Number of puffs of rescue medication | Standard Error 0.079 |
| Placebo Respimat | Use of PRN (Pro re Nata) Rescue Medication Per Day | Week 48 (N=120, 123, 127) | -0.484 Number of puffs of rescue medication | Standard Error 0.079 |
| Tio R2.5 | Use of PRN (Pro re Nata) Rescue Medication Per Day | Week 24 (N=122, 130, 133) | -0.603 Number of puffs of rescue medication | Standard Error 0.077 |
| Tio R2.5 | Use of PRN (Pro re Nata) Rescue Medication Per Day | Week 48 (N=120, 123, 127) | 0.638 Number of puffs of rescue medication | Standard Error 0.078 |
| Tio R5 | Use of PRN (Pro re Nata) Rescue Medication Per Day | Week 24 (N=122, 130, 133) | 0.646 Number of puffs of rescue medication | Standard Error 0.077 |
| Tio R5 | Use of PRN (Pro re Nata) Rescue Medication Per Day | Week 48 (N=120, 123, 127) | 0.685 Number of puffs of rescue medication | Standard Error 0.078 |
Comparison: Week 24p-value: 0.134995% CI: [-0.382, 0.051]Mixed Models Analysis
Comparison: Week 24p-value: 0.058895% CI: [-0.425, 0.008]Mixed Models Analysis
Comparison: Week 48p-value: 0.167595% CI: [-0.372, 0.065]Mixed Models Analysis
Comparison: Week 48p-value: 0.070995% CI: [-0.419, 0.017]Mixed Models Analysis
Secondary
Use of PRN Rescue Medication During Daytime
Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during daytime based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Use of PRN Rescue Medication During Daytime | Week 24 (N=121, 130, 133) | -0.234 Number of puffs of rescue medication | Standard Error 0.055 |
| Placebo Respimat | Use of PRN Rescue Medication During Daytime | Week 48 (N=119, 123, 125) | -0.247 Number of puffs of rescue medication | Standard Error 0.055 |
| Tio R2.5 | Use of PRN Rescue Medication During Daytime | Week 24 (N=121, 130, 133) | -0.350 Number of puffs of rescue medication | Standard Error 0.053 |
| Tio R2.5 | Use of PRN Rescue Medication During Daytime | Week 48 (N=119, 123, 125) | -0.372 Number of puffs of rescue medication | Standard Error 0.053 |
| Tio R5 | Use of PRN Rescue Medication During Daytime | Week 24 (N=121, 130, 133) | -0.375 Number of puffs of rescue medication | Standard Error 0.053 |
| Tio R5 | Use of PRN Rescue Medication During Daytime | Week 48 (N=119, 123, 125) | -0.378 Number of puffs of rescue medication | Standard Error 0.053 |
Comparison: Week 24p-value: 0.074995% CI: [-0.245, 0.012]Mixed Models Analysis
Comparison: Week 24p-value: 0.030595% CI: [-0.269, -0.013]Mixed Models Analysis
Comparison: Week 48p-value: 0.058195% CI: [-0.255, 0.004]Mixed Models Analysis
Comparison: Week 48p-value: 0.046495% CI: [-0.26, -0.002]Mixed Models Analysis
Secondary
Use of PRN Rescue Medication During Nighttime
Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during nighttime based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Time frame: Baseline and Week 24, Baseline and Week 48.
Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Respimat | Use of PRN Rescue Medication During Nighttime | Week 24 (N=122, 130, 130) | -0.178 Number of puffs of rescue medication | Standard Error 0.051 |
| Placebo Respimat | Use of PRN Rescue Medication During Nighttime | Week 48 (N=119, 122, 125) | -0.198 Number of puffs of rescue medication | Standard Error 0.052 |
| Tio R2.5 | Use of PRN Rescue Medication During Nighttime | Week 24 (N=122, 130, 130) | -0.274 Number of puffs of rescue medication | Standard Error 0.05 |
| Tio R2.5 | Use of PRN Rescue Medication During Nighttime | Week 48 (N=119, 122, 125) | -0.298 Number of puffs of rescue medication | Standard Error 0.05 |
| Tio R5 | Use of PRN Rescue Medication During Nighttime | Week 24 (N=122, 130, 130) | -0.304 Number of puffs of rescue medication | Standard Error 0.05 |
| Tio R5 | Use of PRN Rescue Medication During Nighttime | Week 48 (N=119, 122, 125) | -0.301 Number of puffs of rescue medication | Standard Error 0.05 |
Comparison: Week 24p-value: 0.118295% CI: [-0.217, 0.025]Mixed Models Analysis
Comparison: Week 24p-value: 0.040495% CI: [-0.246, -0.006]Mixed Models Analysis
Comparison: Week 48p-value: 0.110595% CI: [-0.221, 0.023]Mixed Models Analysis
Comparison: Week 48p-value: 0.098395% CI: [-0.224, 0.019]Mixed Models Analysis