Comparative Efficacy of Generic Salmeterol Xinafoate/Fluticasone Propionate MDI Fixed Dose Combination and Seretide ® MDI in Asthmatic Patients: An Open Label, Randomized, Phase III Study.

ABSTRACT

The addition of an inhaled long-acting β2-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients. The long-acting β2-agonist (LABA) Salmeterol xinafoate (Salmeterol) and inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) are being made available as a combination product Seretide® pMDI (Salmeterol/ Fluticasone) in a single aerosol inhaler. This randomized, open label, non-inferior, multicentric, 12-week, phase III study compared the efficacy and safety of generic Salmeterol/Fluticasone with commercially available product Seretide®. Materials and methods:Patients aged > 12 years inclusive of either sex (N = 372) with persistent asthma as defined by NHLBI for > 6 months prior to screening were included in the study. After a screening phase (1 week), eligible patients were enrolled in the trial with 2 weeks run in period. Eligible patients were randomized to receive either of the two treatment groups [HFA-Propelled pMDI Salmeterol/Fluticasone (25/250mcg) or HFA-Propelled Seretide® (25/250mcg) pMDI] in a ratio of 11 for the 12- week treatment period. The primary objective was to demonstrate non-inferiority of Salmeterol/Fluticasone versus Seretide®, measured by mean pre-dose forced expiratory volume in the first second (FEV1), at week 12. Results: This study provides evidence for the primary efficacy endpoint that Salmeterol/Fluticasone was statistically as well as clinically non-inferior to Seretide® in the treatment of patients with persistent asthma. This was supported by secondary endpoints which demonstrate that Salmeterol/Fluticasone appeared to be comparable to Seretide® in terms of efficacy for the secondary efficacy endpoints (morning PEFR, evening PEFR, diurnal variability of PEFR, daytime and night-time asthma symptoms score, average need for short acting-β2-agonists, proportion of patients that required rescue medication, patients with nocturnal asthma, patients without asthma symptoms of score 0 and average number of days without asthma symptoms of score 0). Salmeterol/Fluticasone was safe and well tolerated; and safety profile is comparable to comparator Seretide®. Conclusion: The results of study demonstrate that generic and innovator HFA formulations of Salmeterol/Fluticasone are clinically interchangeable. Overall, the study indicates that HFA-Propelled Salmeterol/ Fluticasone (25/250mcg) pMDI was safe, well tolerated and non-inferior in efficacy compared to HFA-Propelled Seretide® (25/250mcg) pMDI.