A Study to Test the Combination of Tiotropium and Olodaterol Using the Respimat® Inhaler in People With Chronic Obstructive Pulmonary Disease (COPD) Who Have Different Abilities to Inhale

Study Overview
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Brief Summary
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To demonstrate the efficacy of inhaled tiotropium + olodaterol via Respimat® on lung function in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) with optimal and sub-optimal Peak Inspiratory Flow Rate (PIFR). Disease severity (moderate to severe) is based on the Global Initiative for Chronic Lung Disease (GOLD) guidelines (GOLD 2 - 3)

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel Group Study to Compare the Efficacy of Inhaled Tiotropium + Olodaterol, Fixed Dose Combination (5 mcg/5mcg) vs. Placebo Delivered by Respimat Inhaler in Patients With Moderate to Severe COPD, Stratified by Peak Inspiratory Flow Rate [TRONARTO].

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium + olodaterol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent in accordance with International Council on Harmonisation Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. Male or female patients, 40 years of age or older. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) >30% and <80% of predicted normal (European Coal and Steel Community (ECSC), [R94-1408]); and a postbronchodilator FEV1/ Functional Residual Capacity (FVC) <70%, at the screening visit. Patients must be current or ex-smokers with a smoking history of more than 10 pack years Patients should meet the peak inspiratory flow rate criteria (optimal or sub-optimal) at the time of randomization depending on which strata is available for inclusion in the study. Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. Patients are expected to be able to perform, according to investigator's judgment, all trial related procedures including: Technically acceptable pulmonary function tests (spirometry) Use of In-Check DIAL G16 device to measure peak inspiratory flow rate. Inhale medication in a competent manner (in the opinion of the investigator) from the Respimat® device Perform technically acceptable body plethysmography measurements. This is applicable only to patients who will consent to the optional trial procedure at the selected sites. Exclusion Criteria: Patients with a significant disease other than chronic obstructive pulmonary disease; a significant disease defined as a disease which, in the opinion of the investigator, and referring to the warnings to be observed as quoted in the locally applicable SmPC or prescribing information, could (i) put the patient at risk because of participation in the trial, (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial. Patients who have had a chronic obstructive pulmonary disease exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to screening visit or during the screening period. Patients who experienced two or more moderate chronic obstructive pulmonary disease exacerbations (exacerbation that required treatment with antibiotics and/or oral corticosteroids), or one or more exacerbation leading to hospitalization within a year prior to visit 1. Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma. Patients taking inhaled corticosteroids (including combinations, e.g. inhaled corticosteroids / Long-Acting β2-agonist) in the 6 months prior to screening visit. Patients being treated with oral corticosteroid medication due to reasons other than chronic obstructive pulmonary disease exacerbation within 6 weeks prior to the screening visit. Patients who have completed a pulmonary rehabilitation program in the 6 weeks prior to screening visit or patients who are currently in a pulmonary rehabilitation program. Further 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Arm<br>Tiotropium + Olodaterol Fixed Dose Combination (FDC) via Respimat | Drug: Tiotropium + olodaterol<br>* Oral Inhalation<br>|
| Placebo Comparator: Placebo Arm<br>Matching placebo via Respimat | Drug: Placebo<br>* Oral Inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment. | FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters. Mean is adjusted mean. A hierarchical testing procedure was used to test the primary endpoint. Each of the tests were considered confirmatory only if all previous tests were successful. | At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) After 4 Weeks of Treatment | Change from baseline in trough Forced Expiratory Volume in one second (FEV1) after 4 weeks of treatment. | At baseline and at week 4. |