Fluticasone/Formoterol Combination Therapy versus Budesonide/Formoterol for the Treatment of Asthma: A Randomized, Controlled, Non-Inferiority Trial of Efficacy and Safety

Abstract

Objectives. The inhaled corticosteroid fluticasone propionate (fluticasone) and the long-acting β₂ agonist formoterol fumarate (formoterol) have been combined in a single aerosol inhaler fluticasone/formoterol (flutiform^®). This study compared the efficacy and safety of fluticasone/formoterol with the combination product budesonide/formoterol (Symbicort^® Turbohaler^®). Methods. A randomized, double-blind, double-dummy, multicenter, Phase 3 study comprising a 7- (±3) day screening, 2–4-week run-in, and 12-week treatment periods. Patients aged ≥12 years with moderate to severe persistent asthma for ≥6 months before screening and forced expiratory volume in one second (FEV₁) 50–80% predicted and ≥15% reversibility following salbutamol inhalation were randomized to fluticasone/formoterol 250/10 μg twice daily (n = 140) or budesonide/formoterol 400/12 μg twice daily (n = 139). Results. Fluticasone/formoterol was comparable to budesonide/formoterol with respect to the primary endpoint, change in pre-dose FEV₁ from baseline to Week 12. The LS mean treatment difference was −0.044 L, with a lower 95% confidence interval (CI) greater than the pre-defined non-inferiority limit of −0.2 L (95% CI: −0.130, 0.043 L; p < 0.001). Non-inferiority was also demonstrated for the secondary endpoints mean change in FEV₁ from baseline (pre-dose) to 2 hours post-dose at Week 12, and discontinuations due to lack of efficacy. Similar results were obtained for both treatment groups for all other secondary endpoints. Fluticasone/formoterol had a good safety profile that was comparable with budesonide/formoterol. Conclusions. This study demonstrated comparable efficacy of fluticasone/formoterol to budesonide/formoterol in terms of the primary endpoint, change in pre-dose FEV₁ from baseline to Week 12. This was supported by comparable results for both treatments for all secondary endpoints.

• asthma
• combination therapy
• fluticasone
• flutiform^®
• formoterol
• pMDI
• Symbicort^®

Acknowledgments

The authors thank all of the study investigators and participants, the members of the study team from Mundipharma Research Limited, and colleagues at SkyePharma.

Declaration of Interest

Anna Bodzenta-Lukaszyk has received speaker fees from AstraZeneca, HAL Allergy, Novartis, Nycomed, and Torrex Chiesi.

Roland Buhl has received reimbursement for attending scientific conferences, and/or fees for speaking and/or consulting from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Nycomed, and Pfizer. The Pulmonary Department at Mainz University Hospital received financial compensation for services performed during participation in clinical trials organized by various pharmaceutical companies.

Beatrix Balint has received reimbursement for attending scientific conferences and/or fees for consulting from AstraZeneca, Boehringer Ingelheim, and Novartis.

Sanjeeva Dissanayake, Mark Lomax, and Kay Spooner are employed by Mundipharma Research Limited.

The study was funded by Mundipharma Research Limited.

Writing assistance was provided by Karen Paine (Mundipharma Research Limited), a member of the European Medical Writers Association (EMWA), in accordance with the CONSORT statement, and EMWA and Good Publication Practice guidelines.