Efficacy and safety profile of fluticasone/formoterol combination therapy compared to its individual components administered concurrently in asthma: a randomised controlled trial

Abstract

Background:

The potent inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting β₂-agonist with a rapid onset of action, formoterol fumarate (formoterol), have now been combined in a single aerosol inhaler, fluticasone/formoterol (flutiform). This study investigated the efficacy and safety of fluticasone/formoterol combination therapy compared with its individual components administered concurrently via two separate inhalers.

Methods:

Patients ≥12 years (N = 210) with mild to moderate–severe persistent, reversible asthma were evenly randomised to 12 weeks of treatment (b.i.d.) with fluticasone/formoterol combination therapy (100/10 μg b.i.d. or 250/10 μg b.i.d.) or fluticasone plus formoterol (Flixotide Evohaler, pMDI, Flovent [HFA]; Foradil, DPI, Foradil Aerolizer) administered concurrently (fluticasone + formoterol; 100 μg + 12 μg b.i.d. or 250 μg + 12 μg b.i.d.) in an open-label, parallel-group, multicentre study. The primary objective of this study was to show non-inferiority of fluticasone/formoterol compared with fluticasone + formoterol based on mean post-dose FEV₁.

Results:

The mean FEV₁ 30–60 minutes post-dose on Day 84 was approximately 2.6 L in both the fluticasone/formoterol combination and the fluticasone + formoterol treatment groups (per protocol sets; treatment difference least squares (LS) mean: −0.03 L; 95% CI: −0.148, 0.081). The lower limit of the 95% CI (−0.148 L) was above the non-inferiority threshold of ≥−0.2 L. Analyses of other pulmonary function tests, patient reported outcomes, rescue medication use, asthma exacerbations and quality of life questionnaires were also comparable. The safety profiles of the two study groups were similar overall.

Conclusions:

Fluticasone/formoterol combination therapy had comparable efficacy to its individual components administered concurrently, when measured by post-dose FEV₁ in patients aged ≥12 years with mild to moderate–severe asthma. The safety and tolerability profile of fluticasone/formoterol combination therapy was similar to that of its individual components administered concurrently. Although this was an open-label study, the results remain compelling: the primary efficacy measure was a physical endpoint and study statisticians were blinded to treatment allocations until analysis was completed.

Trial registration:

EudraCT: 2007-001634-13; US NCT number: NCT00563056.

Keywords::

• Asthma
• Combination therapy
• Fluticasone propionate
• Formoterol fumarate
• ICS/LABA

Transparency

Declaration of funding

This study was sponsored by Mundipharma Research Ltd.

Declaration of financial/other relationships

A.B.-L. has received speaker fees from HAL Allergy, Novartis, Nycomed and Torrex Chiesi. J.N. is involved in carrying out contract research for Mundipharma Research Ltd, Novartis, GlaxoSmithKline, Boehringer Ingelheim and Chiesi. W.S.-B. received funding from Mundipharma Research Ltd for this study and has no other competing interests. K.M. and T.M. are employees of Mundipharma Research Limited.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

Writing assistance, supported by Mundipharma Research Ltd, was provided by Dr Sara Sleigh. The authors would like to thank all of the investigators and study participants, members of the study team at Mundipharma Research Ltd and Mundipharma Research GmbH and Co. KG, and colleagues at Skyepharma.

Previous presentation: Posters of this study were presented in 2011 at the European Respiratory Society (ERS) Conference held 24.09.11–28.09.11 in Amsterdam and the Primary Care Respiratory Society (PCRS) Conference held 07.10.11–08.10.11 in Telford. In 2012, posters were presented at the 16e Congrès de Pneumologie de Langue Française held 27.01.12–29.01.12 in Lyon and the Deutschen Gesellschaft für Pneumology (DGP) Congress Conference held 29.03.12–01.04.12 in Nuremberg.

Notes

*Flutiform is a registered trade mark of Jagotec AG and is used under licence.

†Flixotide and Evohaler are registered trade marks of Glaxo Group Limited.

‡Foradil is a registered trade mark of Astellas Pharma Inc.

*Flutiform is a registered trade mark of Jagotec AG and is used under licence.

†Flixotide and Evohaler are registered trade marks of Glaxo Group Limited.

‡Foradil is a registered trade mark of Astellas Pharma Inc.

*Aerochamber and Aerochamber Plus are registered trade marks of Trudell Medical International.