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

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.

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.

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.

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.