| 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 12. Measured values presented are actually adjusted means. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Mean | Standard Error | litres | | Baseline and 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
| | | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG0000.438± 0.045
- OG0010.550± 0.046
- OG0020.528± 0.045
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | Mixed Models Analysis | | 0.0457 | Stepwise testing of the null hypothesis was used to test the efficacy of Tio R5 and then Tio R2.5, each over placebo. | Mean Difference (Final Values) | 0.111 | Standard Error of the Mean | 0.055 | 2-Sided | 95 | 0.002 | 0.220 | | | Difference calculated as Tio R2.5 minus placebo | No | Superiority or Other | | | |
|
| Secondary | Trough FEV1 Change From Baseline | Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 12. Measured values presented are actually adjusted means. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Mean | Standard Error | litres | | Baseline and 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
| |
| Secondary | FVC peak0-3 Change From Baseline | Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak0-3h) after 12 weeks of treatment. The measured values presented are actually adjusted means. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Mean | Standard Error | Litres | | Baseline and 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
|
| 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 12 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. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Mean | Standard Error | Litres | | Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
|
| 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 AUC0-3h) after 12 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. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Mean | Standard Error | litres | | Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
|
| Secondary | Control of Asthma as Assessed by ACQ6 Score. | Change from baseline in Asthma Control Questionnaire (ACQ) 6 score measured at week 12 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. ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ6. The measured values presented are actually adjusted means. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Mean | Standard Error | units on a scale | | Baseline and 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | |
|
| Secondary | ACQ6 Score Responders | Responder rates based on the ACQ6 score after 12 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. ACQ6 is calculated as the mean of the responses to the first 6 questions of the ACQ6. No statistical testing was performed on ACQ6 responders. | Full Analysis Set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Number | | percentage of participants | | 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | |
|
| Secondary | Control of Asthma as Assessed by ACQ Total Score | Change from baseline in Asthma Control Questionnaire (ACQ) total score measured at week 12. 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 is calculated as the mean of the responses to all 7 questions. The measured values presented are actually adjusted means. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Mean | Standard Error | units on a scale | | Baseline and 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | |
|
| Secondary | ACQ Total Score Responders | Responder rates based on the ACQ total score after 12 weeks of treatment. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≤-0.5), no change (-0.5 \ | Full Analysis Set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. 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. | Posted | | Number | | percentage of participants | | 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 |
|
| 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 12. The measured values presented are actually adjusted means. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. Missing data was imputed by the available data from the patient. Completely missing data were handled by the statistical model. | Posted | | Mean | Standard Error | Number of puffs of rescue medication | | Baseline and 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
|
| 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 12. Measured values presented are actually adjusted means. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. Missing data was imputed by the available data from the patient. Completely missing data were handled by the statistical model. | Posted | | Mean | Standard Error | Number of puffs of rescue medication | | Baseline and 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
|
| 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 12. Measured values presented are actually adjusted means | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. Missing data was imputed by the available data from the patient. Completely missing data were handled by the statistical model. | Posted | | Mean | Standard Error | Number of puffs of rescue medication | | Baseline and 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
|
| Secondary | Time to First Severe Asthma Exacerbation During the 12-week Treatment Period. | Time in days to first severe asthma exacerbation during the 12 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 an initiation of treatment with systemic corticosteroids for at least 3 days or, in case of ongoing and pre-existing systemic corticosteroid therapy, requiring at least doubling of previous daily doses of systemic corticosteroids for at least 3 days. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. | Posted | | Number | | participants | | 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 |
|
| Secondary | Analysis of Time to First Asthma Exacerbation During the 12 Week Treatment Period. | Time in days to first asthma exacerbation during the 12 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. | Full Analysis Set (FAS) was the same as the treated set which included all randomised patients who were dispensed and received at least one documented dose of trial medication. | Posted | | Number | | participants | | 12 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
| |
| Secondary | Clinically Relevant Abnormalities for Physical Examination, ECG, Vital Signs and Laboratory Tests | Clinically relevant abnormalities for physical examination, ECG, vital signs and laboratory tests. New abnormal findings or worsening of baseline conditions were reported as adverse events. | Treated set which included all randomised patients who were dispensed and received, at least one documented dose of trial medication. | Posted | | Number | | percentage of participants | | From first drug administration until 30 days after last drug intake, up to 142 days | | | | ID | Title | Description |
|---|
| OG000 | Placebo Respimat | Inhalation of placebo solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG001 | Tio R2.5 | Inhalation of 2.5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. | | OG002 | Tio R5 | Inhalation of 5mcg tiotropium bromide solution once daily for 12 weeks delivered by the Respimat Inhaler, as add on therapy on top of usual care. |
| |