Demonstration of therapeutic equivalence between Salmeterol/fluticasone Easyhaler and Seretide Diskus

Background: Easyhaler dry powder inhaler containing salmeterol and fluticasone propionate was developed for treatment of asthma and COPD by Orion Corporation Orion Pharma. Aim: Therapeutic equivalence between at least one Easyhaler test product and reference Seretide Diskus was to be demonstrated. Methods: A randomised, open, single dose, 4-period crossover, pharmacokinetic study was carried out in healthy volunteers. Three Easyhaler test products and reference were compared. The dose was 2 inhalations of 50/500 μg/inhalation strength. Pharmacokinetic variables C max , AUC t and AUC 30min (salmeterol only) were calculated. Ratio estimates (Easyhaler/Diskus) of geometric means were tested for non-inferiority (NI) in total systemic exposure (safety surrogate) and bioequivalence (BE) in lung deposition (efficacy surrogate). Hochberg correction was used to adjust significance level due to multiple comparisons. Results: 65 subjects (18-48 years) were randomised and 61 completed the study. For fluticasone propionate Easyhaler test product B showed BE with reference (96.7% CIs for ratios of C max and AUC t within 0.80-1.25). For salmeterol, all the test products were NI in total systemic exposure compared to reference (the upper one-sided 95% CIs for ratios of C max and AUC t max and AUC 30min within 0.80-1.25). Conclusions: Salmeterol/fluticasone Easyhaler test product B was shown to be non-inferior in total systemic exposure and bioequivalent in lung deposition with Seretide Diskus, and therefore, the products can and be considered therapeutically equivalent.