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Comparison of the Pharmacokinetics of Salmeterol and Fluticasone Propionate 50/100 µg Delivered in Combination as a Dry Powder Via a Capsule-Based Inhaler and a Multi-Dose Inhaler

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Abstract

Background and Objectives

The Rotacaps®/Rotahaler® system is a single unit dose inhaler being developed to deliver inhaled salmeterol/fluticasone propionate combination (SFC) as an alternative treatment option to the metered dose inhaler and the multi-dose dry powder inhaler, Diskus®. The aim of this study was to compare the systemic exposure of SFC 50/100 µg following delivery via the Rotacaps®/Rotahaler® and the Diskus®.

Methods

This was an open-label, randomized, cross-over, repeat-dose (3.5 days of twice-daily dosing) study comparing salmeterol and fluticasone propionate systemic exposure following inhaled SFC 50/100 µg delivered via the Rotacaps®/Rotahaler® and Diskus®, in healthy subjects. Pharmacokinetic sampling was conducted over 12 h post-dose on the last day of each treatment. Pharmacokinetic samples were analysed using solid phase extraction followed by high performance liquid chromatography/tandem mass spectrometry. Co-primary endpoints were fluticasone propionate area under the concentration-time curve over the dosing interval (AUC0–τ ) and salmeterol maximum plasma concentration (C max) on the last day of treatment.

Results

Following SFC 50/100 µg Rotacaps®/Rotahaler®, fluticasone propionate and salmeterol systemic exposures were comparable with Diskus® in terms of both AUC0–τ [geometric mean ratio (GMR) with 90 % confidence interval (CI) of Rotahaler®/Diskus® for fluticasone propionate: 0.98 (0.91, 1.06) and salmeterol: 1.04 (0.99, 1.10)] and C max [GMR (90 % CI) for fluticasone propionate: 1.04 (0.94, 1.15) and salmeterol: 0.97 (0.87, 1.08)], meeting the pre-defined criteria for comparability (upper limit of the 90 % CI for the GMRs (Rotahaler®/Diskus®) ≤1.25]. SFC delivered from both inhalers was well tolerated.

Conclusions

SFC 50/100 µg Rotacaps®/Rotahaler® showed comparable fluticasone propionate and salmeterol systemic exposure to Diskus® for all pharmacokinetic endpoints with GMR and both upper and lower limits of 90 % CIs within conventional acceptance criteria for bioequivalence (0.8, 1.25), sufficient for considering progression of the Rotacaps®/Rotahaler® product for further clinical development.

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Acknowledgements

The authors would like to thank Clifford Baxter, GSK Medicines Research Unit, Randwick, Australia, for his role as principal investigator and for providing medical oversight during the conduct of this clinical trial. The Authors would like to acknowledge statistical programming support from Quantitative sciences-India, GSK for their support in statistical analysis of the pharmacokinetic and safety data. The authors would also like to acknowledge editorial support in the form of draft manuscript development, collating of author comments and copyediting which was provided by Kate Hollingworth of Continuous Improvement Ltd. This support was funded by GSK.

Disclosure statement

This study was funded by GSK (Protocol 200260; NCT01890863, NCT: 01540708). RM, KR, AG, MDL and RHC are employees of GSK, and CB was an employee of GSK at the time of study conduct. RM, MDL and RHC own GSK shares. There are no other conflicts of interest to declare.

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Authors and Affiliations

  1. GlaxoSmithKline, Research Triangle Park, NC, USA

    Rashmi Mehta & Margaret D Louey

  2. GlaxoSmithKline Medicines Research Unit, Prince of Wales Hospital, Randwick, Australia

    Kylie Riddell

  3. Quantitative Sciences India, GlaxoSmithKline, Bangalore, India

    Ashutosh Gupta

  4. GlaxoSmithKline, Stockley Park, Uxbridge, UK

    Robert H. Chan

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  1. Rashmi Mehta
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  2. Kylie Riddell
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  3. Ashutosh Gupta
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  4. Margaret D Louey
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  5. Robert H. Chan
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Corresponding author

Correspondence to Rashmi Mehta.

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Mehta, R., Riddell, K., Gupta, A. et al. Comparison of the Pharmacokinetics of Salmeterol and Fluticasone Propionate 50/100 µg Delivered in Combination as a Dry Powder Via a Capsule-Based Inhaler and a Multi-Dose Inhaler. Clin Drug Investig 35, 319–326 (2015). https://doi.org/10.1007/s40261-015-0282-x

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  • DOI: https://doi.org/10.1007/s40261-015-0282-x

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