Characterization of Lung Function Profile of Inhaled Tiotropium + Olodaterol Fixed Dose Combination Compared to Fluticasone Propionate + Salmeterol Fixed Dose Combination in COPD Patients

Study Overview
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Brief Summary
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The objective of the trial is to compare the lung function profile of once daily treatment with tiotropium+olodaterol FDC [2.5/ 5µg and 5/ 5µg] delivered by the RESPIMAT with the lung function profile of twice daily treatment with fluticasone propionate+salmeterol FDC [250/50µg and 500/50µg] delivered by the Accuhaler® after 6 weeks of treatment.

Official Title
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Randomized, Double-blind, Double-dummy, Active-controlled, 4 Period Complete Cross-over Study to Compare the Effect on Lung Function of 6 Weeks Once Daily Treatment With Orally Inhaled Tiotropium+Olodaterol Fixed Dose Combination Delivered by the Respimat® Inhaler vs. 6 Weeks Twice Daily Treatment With Fluticasone Propionate+Salmeterol Fixed Dose Combination Delivered by the Accuhaler® in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: fluticasone propionate
* Drug: salmeterol
* Drug: placebo
* Drug: placebo
* Drug: tiotropium
* Drug: olodaterol
* Drug: olodaterol
* Drug: placebo
* Drug: placebo
* Drug: tiotropium
* Drug: fluticasone propionate
* Drug: salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of chronic obstructive pulmonary disease Relatively stable airway obstruction with a post-bronchodilator 30% </= Forced Expiratory Volume in 1 second (FEV1)<80% of predicted normal and a post-bronchodilator FEV1/(Forced Vital Capacity)FVC <70% Male or female patients, 40 years of age or older Smoking history of more than 10 pack years Ability to perform technically acceptable pulmonary function tests and maintain records Ability to inhale medication in a competent manner from the RESPIMAT Inhaler, Accuhaler and from a metered dose inhaler (MDI) Exclusion criteria: Significant disease other than COPD COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or iv) or hospitalization in the last 3 months. Clinically relevant abnormal lab values History of asthma Diagnosis of thyrotoxicosis Diagnosis of paroxysmal tachycardia History of myocardial infarction Unstable or life-threatening cardiac arrhythmia Hospitalization for heart failure within the past year Known active tuberculosis malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years History of life-threatening pulmonary obstruction History of cystic fibrosis Clinically evident bronchiectasis History of significant alcohol or drug abuse History of thoracotomy with pulmonary resection oral or patch ß-adrenergics Oral corticosteroid medication within 6 weeks prior to Visit 1 Regular use daytime oxygen therapy for more than one hour per day Pulmonary rehabilitation program in the six weeks prior to the screening visit Investigational drug within one month or six half lives (whichever is greater) prior to screening visit Known hypersensitivity to ß-adrenergic drugs, BAC, EDTA Pregnant or nursing women

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: T+O FDC dosage 1<br>Low dose | Drug: olodaterol<br> <br> Drug: placebo<br>* placebo/dummy for blinding purposes<br>Drug: tiotropium<br>* tiotropium low dose<br>|
| Experimental: T+O FDC dosage 2<br>High dose | Drug: placebo<br>* placebo/dummy for blinding purposes<br>Drug: tiotropium<br>* tiotropium high dose<br>Drug: olodaterol<br> <br> |
| Active Comparator: ICS/LABA FDC Dosage 1<br>Low dose | Drug: fluticasone propionate<br>* low dose<br>Drug: salmeterol<br> <br> Drug: placebo<br>* placebo/dummy for blinding purposes<br>|
| Active Comparator: ICS/LABA FDC Dosage 2<br>High dose | Drug: placebo<br>* placebo/dummy for blinding purposes<br>Drug: fluticasone propionate<br>* low dose<br>Drug: salmeterol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC (0-12h) Change From Patient Baseline After 6 Weeks of Treatment | Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 12hours post-dose (AUC 0-12h) [L] after 6 weeks of treatment. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient. | Baseline and 6 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC (0-24h) Change From Patient Baseline After 6 Weeks of Treatment | Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 24 hours post-dose (AUC 0-24h) [L] after 6 weeks of treatment. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient. | Baseline and 6 weeks. | 
| Trough FEV1 Change From Patient Baseline After 6 Weeks of Treatment | Change from patient baseline in Trough Forced Expiratory Volume in one second (FEV1) after 6 weeks of treatment. Trough FEV1 was defined as the mean of the 23h and 23h 50min (minutes) post-dose FEV1 measurements. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient. | Baseline and 6 weeks. | 
| FEV1 AUC (12-24h) Change From Patient Baseline After 6 Weeks of Treatment | Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 12 to 24 hours post-dose (AUC 12-24h) [L] after 6 weeks of treatment. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient. | Baseline and 6 weeks. | 
| FEV1 Peak (0-3h) Change From Patient Baseline After 6 Weeks of Treatment | Change from patient baseline in Forced Expiratory Volume in one second (FEV1) peak (0-3 hours) after 6 weeks of treatment. FEV1 peak (0-3 hours) was defined as the maximum FEV1 value measured within the first three hours post dosing. Measured values presented are actually adjusted means. | Baseline and 6 weeks. |