Olodaterol Bridging Study in Asthma

Study Overview
=================
Brief Summary
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The aim of the study is to establish the olodaterol dose in the ethanolic fixed dose combination (FDC) with BI 54903 which is equivalent in bronchodilator effect and systemic exposure to the 5 µg olodaterol reference dose in the aqueous inhalation solution (AIS).

Official Title
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Single Dose Comparison of 3 Doses of Olodaterol in Double Fixed Dose Combination With BI54903 vs. 3 Doses of Olodaterol Mono in Free Combination

Conditions
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Asthma

Intervention / Treatment
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* Device: Respimat
* Device: Respimat
* Device: Respimat
* Device: Respimat
* Device: Respimat
* Device: Respimat
* Device: Respimat
* Drug: Olodaterol
* Drug: Olodaterol
* Drug: Olodaterol
* Drug: Olodaterol
* Drug: Olodaterol
* Drug: Olodaterol
* Drug: Olodaterol
* Drug: Olodaterol & BI54903
* Drug: Olodaterol & BI54903
* Drug: Olodaterol & BI54903
* Drug: Olodaterol & BI54903
* Drug: Olodaterol & BI54903
* Drug: Olodaterol & BI54903
* Drug: Olodaterol & BI54903
* Drug: BI54903
* Drug: BI54903
* Drug: BI54903
* Drug: BI54903
* Drug: BI54903
* Drug: BI54903
* Drug: BI54903


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Informed Consent Form consistent guidelines and local legislation prior Male or female patients aged at least 18 to 75 years. Diagnosis of asthma according to the 2009 Global Initiative for Asthma (GINA) Guidelines. Maintenance treatment with a low or medium dose of inhaled corticosteroids (ICS) with or without Long-acting beta-adrenergic (LABA), stable dose of inhaled corticosteroids (alone or in a fixed combination with a LABA) for at least for 6 weeks prior to screening. Asthma control questionaire (ACQ)-6 mean score of < 1.5. a. Pre-bronchodilator clinic measured FEV1 =50% and =90% of predicted normal b. FEV1 reversibility: Improvement in FEV1 =12% above baseline and an absolute change of at least 200 ml within 15-30 minutes after administration of 400 µg salbutamol. Never-smokers or ex-smokers with a smoking history of less than 10 pack-years and smoking cessation at least one year prior to screening. Be able to use the inhalers correctly in the opinion of the investigator. Be able to perform all trial related procedures. Exclusion criteria: Significant disease other than asthma. Recent history (i.e. six months or less) of myocardial infarction. Hospitalisation for cardiac failure during the past year. Unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year. Lung diseases other than asthma (e.g. Chronic obstructive pulmonary disease). Active tuberculosis. Malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Thoracotomy with pulmonary resection. Alcohol or drug abuse within the past two years. Pulmonary rehabilitation program Hypersensitivity to LABA drugs, ciclesonide, salmeterol or any other components of the study medication delivery systems. Pregnant or nursing woman. Women of childbearing potential not using a highly effective method of birth control.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
=================
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 |
| --- | --- |
| Placebo Comparator: Placebo + BI 54903<br>patient to receive 2 puffs of respimat A and 2 puffs of respimat B | Device: Respimat<br>* aqueous and ethanolic solution<br>Drug: Olodaterol<br>* aqueous solution<br>Drug: Olodaterol & BI54903<br>* ethanolic solution<br>Drug: BI54903<br>* ethanolic solution<br>|
| Experimental: Olodaterol low dose + BI54903<br>patient to receive 2 puffs of respimat A and 2 puffs of respimat B | Device: Respimat<br>* aqueous and ethanolic solution<br>Drug: Olodaterol<br>* aqueous solution<br>Drug: Olodaterol & BI54903<br>* ethanolic solution<br>Drug: BI54903<br>* ethanolic solution<br>|
| Active Comparator: Olodaterol medium dose + BI54903<br>patient to receive 2 puffs of each device | Device: Respimat<br>* aqueous and ethanolic solution<br>Drug: Olodaterol<br>* aqueous solution<br>Drug: Olodaterol & BI54903<br>* ethanolic solution<br>Drug: BI54903<br>* ethanolic solution<br>|
| Experimental: Olodaterol high dose + BI54903<br>patient to receive 2 puffs of each device | Device: Respimat<br>* aqueous and ethanolic solution<br>Drug: Olodaterol<br>* aqueous solution<br>Drug: Olodaterol & BI54903<br>* ethanolic solution<br>Drug: BI54903<br>* ethanolic solution<br>|
| Experimental: Olodaterol l dose + BI54903<br>patient to receive 2 puffs of each device | Device: Respimat<br>* aqueous and ethanolic solution<br>Drug: Olodaterol<br>* aqueous solution<br>Drug: Olodaterol & BI54903<br>* ethanolic solution<br>Drug: BI54903<br>* ethanolic solution<br>|
| Experimental: Olodaterol m dose + BI54903<br>patient to receive 2 puffs of each device | Device: Respimat<br>* aqueous and ethanolic solution<br>Drug: Olodaterol<br>* aqueous solution<br>Drug: Olodaterol & BI54903<br>* ethanolic solution<br>Drug: BI54903<br>* ethanolic solution<br>|
| Experimental: Olodaterol h dose + BI54903<br>patient to receive 2 puffs of each device | Device: Respimat<br>* aqueous and ethanolic solution<br>Drug: Olodaterol<br>* aqueous solution<br>Drug: Olodaterol & BI54903<br>* ethanolic solution<br>Drug: BI54903<br>* ethanolic solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 (AUC0-12h) FEV1 = Forced expiratory volume in one second, AUC = area under the curve |  | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 (AUC0-24h) |  | 24 hours | 
| FEV1 (AUC12-24h) |  | 12 hours | 
| Peak FEV1 |  | 12 hours |