| Primary | Forced Expiratory Volume (FEV1) Peak (0-3h) Response | The FEV1 peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FEV1 measured within the first 3 hours post dosing and the FEV1 baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | The Full analysis set (FAS) is defined as patients randomised, treated, with baseline data and at least one on-treatment efficacy measurement after 4 weeks on treatment within a period. This patient set is therefore FAS reduced to patients with non-missing FEV1 data. | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 | Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. |
| | Units | Counts |
|---|
| Participants | - OG00074
- OG00173
- OG00274
- OG003
|
| | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG0000.489± 0.047
- OG0010.556± 0.047
- OG0020.546± 0.047
- OG003
|
|
| | 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 model repeated measures (MMRM) | This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect. | 0.0043 | First step of closed testing procedure, where the active treatments are compared to placebo. If this statisical test significant at the 0.05 alpha level then proceed to comparison of the next lower dose to placebo. | Mean Difference (Final Values) | 0.113 | Standard Error of the Mean | 0.039 | | 95 | 0.036 | 0.190 | | | | No | Superiority or Other | |
|
| Secondary | Trough FEV1 Response | The trough FEV1 is defined as the pre-dose FEV1 measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing FEV1 data. | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 | |
|
| Secondary | FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response | FEV1 (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing FEV1 data. | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 |
|
| Secondary | FEV1 Individual Measurements Response at Each Time-point | Individual FEV1 measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing FEV1 data. | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 |
|
| Secondary | Forced Vital Capacity (FVC) Peak (0-3h) Response | The FVC peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FVC measured within the first 3 hours post dosing and the FVC baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing FVC data. | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 |
|
| Secondary | FVC Trough Response | The trough FVC response is defined as the pre-dose FVC measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing FVC data. | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 | |
|
| Secondary | FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response | FVC (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing FVC data. | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 |
|
| Secondary | FVC Individual Measurements at Each Time-point | Individual FVC measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing FVC data. | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 |
|
| Secondary | Forced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point | FEF 25-75% is the mean forced expiratory flow between 25% and 75% of the FVC determined at the end of the 4-week treatment period. This is often referred to as the maximum midexpiratory flow. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing FEF data | Posted | | Least Squares Mean | Standard Error | Litre | | Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | |
|
| Secondary | Mean Morning Peak Expiratory Flow (PEF) Response | Mean morning PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing morning PEF data | Posted | | Least Squares Mean | Standard Error | Litre/min | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 | |
|
| Secondary | Mean Evening PEF Response | Mean evening PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing evening PEF data | Posted | | Least Squares Mean | Standard Error | Litre/min | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 | Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. |
|
| Secondary | Change From Baseline in the Number of Puffs of Rescue Medication Per Day | Mean number of inhalations (puffs) of unscheduled rescue salbutamol therapy during whole day. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing data for rescue medication | Posted | | Least Squares Mean | Standard Error | Puffs/day | | Baseline and 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 | |
|
| Secondary | Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ) | ACQ is a questionnaire consisting of a seven point Likert scale ranging from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The scale describes the frequency and severity of asthma symptoms. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing ACQ data | Posted | | Least Squares Mean | Standard Error | Units on a scale | | 4 weeks | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 |
|
| Secondary | Change From Baseline in Mean Number of Nighttime Awakenings | Mean number of nighttime awakenings due to asthma symptoms as assessed by patients eDiary incorporated in the AM3® device. Analysis adjusted for treatment, period, patient and baseline using a mixed model. | FAS with non-missing data for nighttime awakenings | Posted | | Least Squares Mean | Standard Error | Night awakenings per week | | Baseline and last week of treatment (week 4) | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG001 | Tio R1.25 | Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG002 | Tio R2.5 | Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. | | OG003 | Tio R5 |
|