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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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Abstract

Objective

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

Patients aged 12 to 82 years with moderate to severe asthma who were symptomatic on existing inhaled corticosteroid therapy.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgements

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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Authors and Affiliations

  1. Atrium Hospital, Heerlen, The Netherlands

    J. A. van Noord

  2. Tartu University Lung Clinic, Tartu, Estonia

    H. Lill

  3. Servicio de Alergia, Hospital de Gran Canaria Doctor Negrin, Las Palmas de Gran Canaria, Spain

    T. Carrillo Diaz

  4. Geerdinksweg, Hengelo, The Netherlands

    A. P. Greefhorst

  5. Respiratory Therapeutic Development, Glaxo Wellcome Research and Development, Uxbridge, England

    P. Davies

Authors
  1. J. A. van Noord
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  2. H. Lill
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  3. T. Carrillo Diaz
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  4. A. P. Greefhorst
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  5. P. Davies
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van Noord, J.A., Lill, H., Diaz, T.C. et al. 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. Clin. Drug Investig. 21, 243–255 (2001). https://doi.org/10.2165/00044011-200121040-00002

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