Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
This is a multi-centre, randomised, double-blinded, active-controlled, 2-way cross over trial to assess the effects of once daily administration of orally inhaled tiotropium + olodaterol FDC or tiotropium (both delivered by the RESPIMAT Inhaler) on pulmonary function (lung hyperinflation), exercise capacity (6-minute walk distance) and physical activities after 6 weeks of treatment in Japanese patients with Chronic Obstructive Pulmonary Disease.
Interventions
DRUGtiotropium
fixed dose combination
DRUGolodaterol
fixed dose combination
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients must sign an informed consent consistent with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, which includes medication washout and restrictions. * All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) and must meet the following spirometric criteria: Patients must have relatively stable airway obstruction with a post-bronchodilator Forced expiratory volume in one second (FEV1) \< 80% of predicted normal and post-bronchodilator FEV1/forced vital capacity (FVC) \< 70% at Visit 1. * Male or female patients, aged \>= 40 years. * Patients must be current or ex-smokers with a smoking history of more than 10 pack years. Patients who have never smoked cigarettes must be excluded. * Patients with score on the modified Medical Research Council (mMRC) \>= 1. * Patients who walk \< 400 meters of 6MWT and have a score on the modified Borg \>= 4 at the end of 6 minute walk test (6MWT) at Visit 2. * Patients must be able to perform technically acceptable pulmonary function tests (spirometry), to use the physical activity monitor and must be able to complete 6MWT during the study period as required in the protocol. * Patients must be able to inhale medication in a competent manner from the RESPIMAT Inhaler and from a metered dose inhaler.
Exclusion criteria
* Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may put the patient at risk because of participation in the study, influence the results of the study and cause concern regarding the patient's ability to participate in the study. * Patients with clinically relevant abnormal baseline haematology, blood chemistry,urinalysis or creatinine \> x2 upper limit of normal (ULN) will be excluded regardless of clinical condition (a repeat laboratory evaluation can be conducted if deemed necessary by the investigator). * Patients with a current documented diagnosis of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma. * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inspiratory Capacity at Rest Measured at 60 Minutes Post-dose | Day 43, 60 minutes post-dose after 6 weeks of each treatment | At day 43 inspiratory capacity at rest measured at 60 minutes post-dose, after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Step Per Day (Step/Day) | 2 weeks prior to Week 6 per treatment | At day 43 adjusted mean (SE) of average number of step per day \[step/day\] treatment comparisons in measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
| Average Daily Duration (Minutes) of ≥ 4 Metabolic Equivalents (METs) | 2 weeks prior to Week 6 per treatment | At day 43 adjusted mean (SE) of average daily duration \[minute\] of ≥ 4 METs treatment comparisons measured by the activity monitor in the 2 weeks prior to week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
| Average Daily Duration (Minutes) of ≥ 3 Metabolic Equivalents (METs) | 2 weeks prior to Week 6 per treatment | At day 43 adjusted mean (SE) of average daily duration \[minute\] of ≥ 3 METs treatment comparisons measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
| Average Daily Duration (Minutes) of ≥ 2 Metabolic Equivalents (METs) | 2 weeks prior to Week 6 per treatment | At day 43 adjusted mean (SE) of average daily duration \[minute\] of ≥ 2 METs treatment comparison measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
| 6-minute Walk Distance [Meter] | Day 43, 60 minutes post-dose after 6 weeks of each treatment | 6-minute walk distance \[Meter\] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
| 60 Minutes Post-dose Slow Vital Capacity (SVC) (in Litre) | Day 43, 60 minutes post-dose after 6 weeks of each treatment | At day 43 adjusted mean (SE) of 60 minute post-dose slow vital capacity \[Litre\] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
| 30 Minutes Post-dose Forced Expiratory Volume in One Second (FEV1) (in Litre) | Day 43, 30 minutes post-dose after 6 weeks of each treatment | At day 43 adjusted mean (SE) of 30 minute post-dose forced expiratory volume in one second (FEV1) \[Litre\] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
| 30 Minutes Post-dose Forced Vital Capacity (FVC) (in Litre) | Day 43, 30 minutes post-dose after 6 weeks of each treatment | At day 43 adjusted mean (SE) of 30 minute post-dose forced vital capacity (FVC) \[Litre\] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
| Average Daily Active Strength (Metabolic Equivalents*Minutes) of ≥ 3 METs | 2 weeks prior to Week 6 per treatment | At day 43 adjusted mean (SE) of average daily active strength \[METs x minute\] of \>=3 METs treatment comparisons measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. |
Countries
Japan
Participant flow
Recruitment details
This was a randomised, double-blind, active-controlled, 2-way crossover trial to assess the effects of once daily treatment of orally inhaled Tiotropium + Olodaterol FDC 5 μg/5 μg or Tiotropium 5 μg over 12 weeks of treatment in Japanese patients with Chronic obstructive pulmonary disease (COPD).
Pre-assignment details
All patients were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were violated.
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 |
| Period 1 | Other than listed above | 1 | 2 |
| Period 1 | Unexpected worsening of disease | 2 | 0 |
| Period 2 | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Total |
|---|---|
| Age, Continuous | 72.8 Years STANDARD_DEVIATION 7.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 184 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 182 | 0 / 180 |
| other Total, other adverse events | 11 / 182 | 18 / 180 |
| serious Total, serious adverse events | 7 / 182 | 7 / 180 |
Outcome results
Primary
Inspiratory Capacity at Rest Measured at 60 Minutes Post-dose
At day 43 inspiratory capacity at rest measured at 60 minutes post-dose, after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Inspiratory Capacity at Rest Measured at 60 Minutes Post-dose | 1.875 Litre (L) | Standard Error 0.019 |
| Tiotropium + Olodaterol 5/5 μg | Inspiratory Capacity at Rest Measured at 60 Minutes Post-dose | 1.990 Litre (L) | Standard Error 0.019 |
p-value: <0.00195% CI: [0.077, 0.153]Mixed Models Analysis
Secondary
30 Minutes Post-dose Forced Expiratory Volume in One Second (FEV1) (in Litre)
At day 43 adjusted mean (SE) of 30 minute post-dose forced expiratory volume in one second (FEV1) \[Litre\] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 30 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | 30 Minutes Post-dose Forced Expiratory Volume in One Second (FEV1) (in Litre) | 1.169 Litre (L) | Standard Error 0.011 |
| Tiotropium + Olodaterol 5/5 μg | 30 Minutes Post-dose Forced Expiratory Volume in One Second (FEV1) (in Litre) | 1.275 Litre (L) | Standard Error 0.011 |
p-value: <0.000195% CI: [0.088, 0.123]Mixed Models Analysis
Secondary
30 Minutes Post-dose Forced Vital Capacity (FVC) (in Litre)
At day 43 adjusted mean (SE) of 30 minute post-dose forced vital capacity (FVC) \[Litre\] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 30 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | 30 Minutes Post-dose Forced Vital Capacity (FVC) (in Litre) | 2.857 Litre (L) | Standard Error 0.021 |
| Tiotropium + Olodaterol 5/5 μg | 30 Minutes Post-dose Forced Vital Capacity (FVC) (in Litre) | 3.020 Litre (L) | Standard Error 0.021 |
p-value: <0.000195% CI: [0.13, 0.197]Mixed Models Analysis
Secondary
60 Minutes Post-dose Slow Vital Capacity (SVC) (in Litre)
At day 43 adjusted mean (SE) of 60 minute post-dose slow vital capacity \[Litre\] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | 60 Minutes Post-dose Slow Vital Capacity (SVC) (in Litre) | 2.962 Litre (L) | Standard Error 0.021 |
| Tiotropium + Olodaterol 5/5 μg | 60 Minutes Post-dose Slow Vital Capacity (SVC) (in Litre) | 3.096 Litre (L) | Standard Error 0.021 |
p-value: <0.000195% CI: [0.091, 0.176]Mixed Models Analysis
Secondary
6-minute Walk Distance [Meter]
6-minute walk distance \[Meter\] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | 6-minute Walk Distance [Meter] | 307.356 Meter (m) | Standard Error 5.17 |
| Tiotropium + Olodaterol 5/5 μg | 6-minute Walk Distance [Meter] | 311.524 Meter (m) | Standard Error 5.17 |
p-value: 0.429195% CI: [-6.211, 14.548]Mixed Models Analysis
Secondary
Average Daily Active Strength (Metabolic Equivalents*Minutes) of ≥ 3 METs
At day 43 adjusted mean (SE) of average daily active strength \[METs x minute\] of \>=3 METs treatment comparisons measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: 2 weeks prior to Week 6 per treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Average Daily Active Strength (Metabolic Equivalents*Minutes) of ≥ 3 METs | 148.647 Metabolic equivalents * minutes | Standard Error 3.723 |
| Tiotropium + Olodaterol 5/5 μg | Average Daily Active Strength (Metabolic Equivalents*Minutes) of ≥ 3 METs | 151.067 Metabolic equivalents * minutes | Standard Error 3.737 |
p-value: 0.495595% CI: [-4.572, 9.411]Mixed Models Analysis
Secondary
Average Daily Duration (Minutes) of ≥ 2 Metabolic Equivalents (METs)
At day 43 adjusted mean (SE) of average daily duration \[minute\] of ≥ 2 METs treatment comparison measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: 2 weeks prior to Week 6 per treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Average Daily Duration (Minutes) of ≥ 2 Metabolic Equivalents (METs) | 171.935 minute | Standard Error 2.506 |
| Tiotropium + Olodaterol 5/5 μg | Average Daily Duration (Minutes) of ≥ 2 Metabolic Equivalents (METs) | 174.192 minute | Standard Error 2.517 |
p-value: 0.394995% CI: [-2.966, 7.481]Mixed Models Analysis
Secondary
Average Daily Duration (Minutes) of ≥ 3 Metabolic Equivalents (METs)
At day 43 adjusted mean (SE) of average daily duration \[minute\] of ≥ 3 METs treatment comparisons measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: 2 weeks prior to Week 6 per treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Average Daily Duration (Minutes) of ≥ 3 Metabolic Equivalents (METs) | 44.662 minute | Standard Error 0.979 |
| Tiotropium + Olodaterol 5/5 μg | Average Daily Duration (Minutes) of ≥ 3 Metabolic Equivalents (METs) | 45.601 minute | Standard Error 0.979 |
p-value: 0.352495% CI: [-1.048, 2.926]Mixed Models Analysis
Secondary
Average Daily Duration (Minutes) of ≥ 4 Metabolic Equivalents (METs)
At day 43 adjusted mean (SE) of average daily duration \[minute\] of ≥ 4 METs treatment comparisons measured by the activity monitor in the 2 weeks prior to week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: 2 weeks prior to Week 6 per treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Average Daily Duration (Minutes) of ≥ 4 Metabolic Equivalents (METs) | 10.206 minute | Standard Error 0.497 |
| Tiotropium + Olodaterol 5/5 μg | Average Daily Duration (Minutes) of ≥ 4 Metabolic Equivalents (METs) | 9.914 minute | Standard Error 0.499 |
p-value: 0.533895% CI: [-1.217, 0.633]Mixed Models Analysis
Secondary
Average Number of Step Per Day (Step/Day)
At day 43 adjusted mean (SE) of average number of step per day \[step/day\] treatment comparisons in measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: 2 weeks prior to Week 6 per treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Average Number of Step Per Day (Step/Day) | 3550.400 step/day | Standard Error 93.123 |
| Tiotropium + Olodaterol 5/5 μg | Average Number of Step Per Day (Step/Day) | 3559.901 step/day | Standard Error 93.46 |
p-value: 0.909895% CI: [-155.692, 174.694]Mixed Models Analysis
Post Hoc
Inspiratory Capacity [Litre] Test Comparisons of 6-Minute Walk Treatment (6MWT) in-Completer at Treatment Period
At day 43 adjusted mean (standard error) of inspiratory capacity \[Litre\] test comparisons after 6 weeks of each treatment for 6MWT in-completer at treatment period. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Inspiratory Capacity [Litre] Test Comparisons of 6-Minute Walk Treatment (6MWT) in-Completer at Treatment Period | 1.738 Litre (L) | Standard Error 0.024 |
| Tiotropium + Olodaterol 5/5 μg | Inspiratory Capacity [Litre] Test Comparisons of 6-Minute Walk Treatment (6MWT) in-Completer at Treatment Period | 1.820 Litre (L) | Standard Error 0.024 |
p-value: <0.000195% CI: [0.056, 0.108]Mixed Models Analysis
Post Hoc
Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Baseline Period
At day 43 adjusted mean (standard error) of inspiratory capacity \[Litre\] test comparisons after 6 weeks of each treatment for 6MWT completer at baseline period. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Baseline Period | 1.925 Litre (L) | Standard Error 0.021 |
| Tiotropium + Olodaterol 5/5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Baseline Period | 2.053 Litre (L) | Standard Error 0.021 |
p-value: <0.000195% CI: [0.1, 0.156]Mixed Models Analysis
Post Hoc
Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Treatment Period
At day 43 adjusted mean (standard error) of inspiratory capacity \[Litre\] test comparisons after 6 weeks of each treatment for 6MWT completer at treatment period. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Treatment Period | 1.940 Litre (L) | Standard Error 0.022 |
| Tiotropium + Olodaterol 5/5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Treatment Period | 2.072 Litre (L) | Standard Error 0.022 |
p-value: <0.000195% CI: [0.103, 0.162]Mixed Models Analysis
Post Hoc
Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) in-Completer at Baseline Period
At day 43 adjusted mean (standard error) of inspiratory capacity \[Litre\] test comparisons after 6 weeks of each test for 6MWT in-completer at baseline period. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) in-Completer at Baseline Period | 1.744 Litre (L) | Standard Error 0.026 |
| Tiotropium + Olodaterol 5/5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) in-Completer at Baseline Period | 1.830 Litre (L) | Standard Error 0.026 |
p-value: <0.000195% CI: [0.058, 0.114]Mixed Models Analysis
Post Hoc
Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I/II
At day 43 adjusted mean (standard error) of inspiratory capacity \[Litre\] treatment comparisons after 6 weeks of each treatment for subgroup of GOLD stage I/II. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I/II | 2.023 Litre (L) | Standard Error 0.023 |
| Tiotropium + Olodaterol 5/5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I/II | 2.106 Litre (L) | Standard Error 0.023 |
p-value: <0.000195% CI: [0.059, 0.108]Mixed Models Analysis
Post Hoc
Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage III/IV
At day 43 adjusted mean (standard error) of inspiratory capacity \[Litre\] treatment comparisons after 6 weeks of each treatment for subgroup of GOLD stage III/IV. Adjusted mean was entered instead of mean in statistical analysis.
Time frame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Population: Full analysis set (FAS): FAS includes participants who had baseline measurement and at least 1 post-baseline measurement for the primary endpoint or a secondary endpoint. The FAS was used for the efficacy analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium 5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage III/IV | 1.697 Litre (L) | Standard Error 0.026 |
| Tiotropium + Olodaterol 5/5 μg | Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage III/IV | 1.849 Litre (L) | Standard Error 0.026 |
p-value: <0.000195% CI: [0.114, 0.189]Mixed Models Analysis