Comparing the Efficacy of Tiotropium + Olodaterol Fixed Dose Combination (FDC) Over Tiotropium in Improvement of Lung Hyperinflation, Exercise Capacity and Physical Activity in Japanese COPD Patients

Study Overview
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Brief Summary
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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.

Official Title
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A Randomised, Double-blinded, Active-controlled 2-way Cross Over Trial to Assess the Effects of 6 Weeks Treatment of Once Daily Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination Delivered by RESPIMAT Inhaler Compared With Tiotropium Delivered by RESPIMAT Inhaler on Lung Hyperinflation, Exercise Capacity and Physical Activity in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: tiotropium
* Drug: olodaterol
* Drug: tiotropium


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tiotropium + olodaterol<br>inhalation two puffs from the RESPIMAT inhaler, once a day, in the morning | Drug: tiotropium<br>* fixed dose combination<br>Drug: olodaterol<br>* fixed dose combination<br>|
| Active Comparator: tiotropium<br>inhalation two puffs from the RESPIMAT inhaler, once a day, in the morning | Drug: tiotropium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 43, 60 minutes post-dose after 6 weeks of each treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 43, 60 minutes post-dose after 6 weeks of each treatment | 
| 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. | 2 weeks prior to Week 6 per treatment | 
| 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. | 2 weeks prior to Week 6 per treatment | 
| 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. | 2 weeks prior to Week 6 per treatment | 
| 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. | 2 weeks prior to Week 6 per treatment | 
| 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. | 2 weeks prior to Week 6 per treatment | 
| 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. | Day 43, 60 minutes post-dose after 6 weeks of each treatment | 
| 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. | Day 43, 30 minutes post-dose after 6 weeks of each treatment | 
| 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. | Day 43, 30 minutes post-dose after 6 weeks of each treatment |