Single Dose Study of the Fluticasone/Salmeterol (500/50 μg) Administered With Elpenhaler® Versus Diskus®

Study Overview
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Brief Summary
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The aim of this study is to establish the therapeutic equivalence between the test (Fluticasone/Salmeterol administered with Elpenhaler®, Rolenium®) and the reference formulation (Seretide®, administered with Diskus®), both containing 500/50μg of the Fluticasone/Salmeterol combination. The study will be conducted in a randomized, double-blind, double-dummy, 2x2 crossover fashion.

Detailed Description
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In case of inhaled products, it is not possible to follow the classic scheme, based on similarity of plasma concentration-time behavior of parent drug in assessing bioequivalence. For this reason, a pharmacodynamic study was designed in order to assess the therapeutic equivalence of the new formulation of Fluticasone/Salmeterol with the innovative one. The test and reference Fluticasone/Salmeterol formulations will be compared in terms of their bronchodilator effects in lung function. Forced Expiratory Volume in 1 second (FEV1) will be the primary efficacy measure and will be measured in such a way that a similar time-dependent increase in pulmonary function can be demonstrated for both Fluticasone/Salmeterol formulations in patients with asthma. In terms of safety comparison, repeated measurements of adverse events, vital signs, heart rate, blood hematology and biochemistry as well as ECG changes will enable the establishment of the similar safety profile of the test and reference Fluticasone/Salmeterol combinations.

Official Title
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Phase III Therapeutic Evaluation Study Comparing the Efficacy and Safety of the Fluticasone/Salmeterol (500/50 μg) Combination Administered With Elpenhaler® (Rolenium®) Versus the Innovative One (Seretide Diskus®) in Patients With Asthma.

Conditions
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Asthma

Intervention / Treatment
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* Drug: Elpenhaler active - Diskus placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-65 years, diagnosis of asthma of 6 months, FEV1 ≥ 50% and ≤ 80% predicted, reversibility of at least 12%, stable asthma for at least 4 weeks, inhaled steroids (ICS) at a stable dose within the previous 30 days, PIF 30 - 90 lt/min and informed consent. Exclusion Criteria: history of other pulmonary disease, asthma exacerbation or respiratory infection within the previous 4 weeks, hospitalization for acute asthmatic symptoms requiring parenteral steroids or oral steroid dose increase, within the previous 30 days, heavy smokers, change of asthma medication within the previous 4 weeks, seasonal asthma alone, history of severe heart disease, pregnancy or lactation, use of a β-blocker, of a NSAID or an antiallergic/antihistaminic medication within 2 weeks prior to screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elpenhaler Active - Diskus Placebo<br>Patients on treatment with both devices, Elpenhaler and Diskus, first active substance, second placebo. | Drug: Elpenhaler active - Diskus placebo<br>* randomized, double-blind, double-dummy, 2-way crossover, single dose study, comparing the efficacy and safety of the Fluticasone/Salmeterol (500/50 μg) combination administered with Elpenhaler® (Rolenium®) versus the innovative one (Seretide Diskus®) in patients with asthma.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary variable will be the 12-hour average FEV1 [area under the FEV1 versus time curve divided by 12 (FEV1 AUC0-12/12)]. | To establish the therapeutic equivalence between the Fluticasone/Salmeterol combination administered with Elpenhaler® (Rolenium®) and the innovative one (Seretide Diskus®) in terms of their bronchodilator effect in lung function. | 0 (baseline), Visit 1 (3-7 days), Visit 2 (3-7 days), Telephone Contact Follow up (3-7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The FEV1 values over time for the 12-hour observation period | To compare the efficacy and safety profile of the two Fluticasone/Salmeterol formulations in patients with asthma. | 0 (baseline), Visit 1 (3-7 days), Visit 2 (3-7 days), Telephone Contact Follow up (3-7 days) | 
| Time to peak FEV1 | To compare the effiacy and safety profile of the two Fluticasone/Salmeterol formulations in patients with asthma | 0 (baseline), Visit 1 (3-7 days), Visit 2 (3-7 days), Telephone Contact Follow up (3-7 days) | 
| Time to peak FEV1 maximum value | same as FEV1 | same as FEV1 |