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
- 97 Downloads
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.
KeywordsFluticasone Propionate Salmeterol Peak Expiratory Flow Beclomethasone Dipropionate Morning Peak Expiratory Flow
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.
- 7.British Thoracic Society. The British guidelines on asthma management 1995 review and position statement. Thorax 1997; 52 Suppl. 1: S1–21Google Scholar
- 8.National Institutes of Health, National Heart Lung and Blood Institute. Guidelines for the diagnosis and management of asthma. Expert panel report 2. July 1997. NIH publication no.: 97-4051Google Scholar
- 9.Global Initiative for Asthma (GINA). Pocket guide for asthma management and prevention. National Institutes of Health, National Heart, Lung and Blood Institute. November 1998. NIH publication no.: 96-3659BGoogle Scholar
- 10.Malton A, Sumby BS, Smith IJ. A comparison of in-vitro drug delivery from two multi-dose powder inhalation devices. Eur J Clin Res 1995; 7: 177–93Google Scholar
- 11.Malton A, Sumby BS, Dandiker Y. A comparison of in-vitro drug delivery from salbutamol Diskus and terbutaline Turbuhaler inhalers. J Pharm Med 1996; 6: 35–48Google Scholar
- 12.Johal B, Gibson GJ, Small T, et al. Use of inhalation profiles from patients with severe obstructive lung disease using the Diskus inhaler and Turbuhaler inhaler to evaluate device performance ex vivo. Eur Respir J 1997; 10: 258sGoogle Scholar
- 13.Conway J, Smith S, Schreiber J, et al. Comparison of peak pressure drops through powder inhalers drug inspiration at maximum flow rate. Am J Respir Crit Care Med 1996; 153: A59Google Scholar
- 14.Luyt D, Vermeiden J, Johnson L, et al. A comparison of the ease of handling of the Diskus/Accuhaler inhaler and the Turbuhaler inhaler in children aged 6–12 years with asthma. J Aerosol Med 1995; 8: 105Google Scholar
- 22.Montreal protocol on substances that deplete the ozone layer. ILM 1987 Sept 16; 1541Google Scholar
- 23.Committee for Proprietary Medicinal Products. The note for guidance on replacement CFCs in metered dose inhalation products. 1993. European Union CPMP guidelines III/5462/93 Rev 1Google Scholar
- 25.Quanjer PH, Tammeling GJ, Cotes JE, et al. Lung volumes and forced ventilatory flows. Eur Respir J 1993; 6 Suppl. 16: 5–40Google Scholar