Clinical Equivalence of a Salmeterol/Fluticasone Propionate Combination Product (50/500μg) Delivered via a Chlorofluorocarbon-Free Metered-Dose Inhaler with the Diskus™ in Patients with Moderate to Severe Asthma
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To demonstrate equivalent efficacy and comparable tolerability of two inhaled combined formulations of salmeterol/fluticasone propionate (SALM/FP) 50/500μg twice daily in asthma patients.
Design and Setting
Multicentre, double-blind, parallel-group study.
Patients aged 12 to 82 years with moderate to severe asthma who were symptomatic on existing inhaled corticosteroid therapy.
176 patients were randomised to SALM/FP 50/500μg twice daily via a novel hydrofluoroalkane (HEA) metered-dose inhaler (MDI; 25/250μg per actuation), and 161 received the same dosage of SALM/FP via a dry powder Diskus™ inhaler (50/500μg) for 12 weeks. A third group of patients (n = 172) received the same dosage of steroid, FP 500μg twice daily, alone via a chlorofluorocarbon (CFC) MDI (250μg per actuation). The primary efficacy parameter was change in morning peak expiratory flow (PEF) over weeks 1 to 12.
The SALM/FP MDI was clinically equivalent to the SALM/FP Diskus™ for the mean change in morning PEF over weeks 1 to 12 [adjusted mean increases 50 and 48 L/min, respectively; treatment difference −2 L/min; 95% confidence interval (CI):−11 to 7 L/min]. The SALM/FPMDI produced significantly greater improvements in morning PEF than the FPMDI (difference: −23 L/min; 95% CI: −32 to −14), with superiority for all secondary efficacy measures. All three treatments were well tolerated, with similar profiles and incidences of adverse events.
At a dosage of 50/500μg twice daily, the SALM/FP 25/250μg HFA MDI (two actuations twice daily) is clinically equivalent to the SALM/FP 50/500μg Diskus™ (one actuation twice daily). The availability of two formulations offers patients a choice of delivery systems when switching to combination therapy with SALM/FP.
The authors would like to thank all the investigators who participated in the study: Dr M. de Jonghe, Dr W. Demedts, Dr J. Martinot, Dr D. Rozen, Dr G. Vandermoten (Belgium); Dr H. Lill, Prof. I. Jannus-Prulijan, Dr P. Pullisaar (Estonia); Dr T. Karakorpi, Dr R. Kauppinen, Dr J. Kotaniemi, Dr P. Nieminen (Finland); Prof. M. Aubier, Prof D. Dusser, Dr E. Fournier, Prof. M. Fournier, Dr J-P. Grignet, Dr M. Grosclaude, Dr N. Grunchec, Dr M. Legendre, Dr J-P. Maffre, Dr J. Robert (France); Dr I. Herjavecz, Prof. P. Kraszko, Dr P. Magyar, Dr H. Zibotics (Hungary); Dr L. Clancy, Dr K. Ward (Ireland); Dr A. Grinberga, Prof. V. Sillins (Latvia); Dr R. Sakalauskas, Prof. B. Satkauskas (Lithuania);Prof. P. Carlos, Dr R. Neveda, Dr J. Roldao Vieira (Portugal); Prof. T. Cheng, Dr T. Khim (Singapore); Dr S. Bardagi, Dr T. Carrillo Diaz, Dr L. Fernadez de Corres, Dr J. Garcia, Dr N. Gonzalez, Dr C. Picado (Spain); Dr L. Lazer, Dr H. Matsol, Dr B. Olsson, Dr E. Ostling-Kulling, Dr M. Palmqvist, Dr M. Soderberg, Prof. G. Stalenheim, Dr J. Ziegler (Sweden); Dr C. Apap, Dr J. Creemers, Dr D. de Munck, Dr E. Dubois, Dr W. Evers, Dr A. Greefhorst, Dr C. Hensing, Dr H. Pasma, Dr W. Pieters, Dr W. Strankinga, Dr A. van Harreveld, Dr J. van Noord, Dr J. Westbroek (The Netherlands).
This study was sponsored by Glaxo Wellcome.
Seretide™, Diskus™ and Ventolin™ are trademarks of the Glaxo Wellcome group.
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