Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial
- William W Busse1,
- Eugene R Bleecker2,
- Eric D Bateman3,
- Jan Lötvall4,
- Richard Forth5,
- Angela M Davis5,
- Loretta Jacques6,
- Brett Haumann6,
- Ashley Woodcock7
- 1Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA
- 2Center for Genomics and Personalized Medicine, Wake Forest University Health Sciences Winston-Salem, North Carolina, USA
- 3Department of Medicine, University of Cape Town, Cape Town, South Africa
- 4Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden
- 5Respiratory Medicines Development Center, GlaxoSmithKline, RTP, North Carolina, USA
- 6Respiratory Medicines Development Centre, GlaxoSmithKline, London, UK
- 7School of Translational Medicine, University of Manchester, Manchester, UK
- Correspondence to Professor William W Busse, Department of Medicine, University of Wisconsin, K4/910 CSC, 600 Highland Avenue, Madison, WI 53792, USA;
Contributors All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. WWB, ERB, EBD, JL, RF, BH, AW participated in concept approval, reviewed data and edited the manuscript. AMD was the clinical investigation leader, contributed to running the study and edited the manuscript. RF conducted statistical analysis of the data and edited the manuscript.
- Received 6 April 2011
- Accepted 6 July 2011
- Published Online First 9 August 2011
Background Fluticasone furoate (FF) is a novel inhaled corticosteroid with 24 h activity. FF is being developed as a once-daily treatment in combination with the long-acting β2 agonist vilanterol trifenatate for asthma and chronic obstructive pulmonary disease.
Objectives To determine the optimal dose(s) of FF for treating patients with asthma.
Methods An 8-week multicentre, randomised, double-blind study. 627 patients with persistent moderate-to-severe asthma, symptomatic on medium-dose inhaled corticosteroid therapy, were randomised to placebo, FF 200, 400, 600 or 800 μg (once daily in the evening using a novel dry powder inhaler), or fluticasone propionate 500 μg twice daily (via Diskus™/Accuhaler™). The primary efficacy measure was mean change from baseline in pre-dose evening forced expiratory volume in one second (FEV1). Other endpoints included morning and evening peak expiratory flow, and rescue/symptom-free 24 h periods.
Results Each dose was significantly superior to placebo for the primary endpoint (p<0.001) with efficacy at least similar to that reported with fluticasone propionate. There was no dose–response relationship across the FF doses studied. Peak expiratory flow improved in all groups (p<0.001 vs placebo), and there were significant treatment effects on rescue/symptom-free 24 h periods with all active treatments. FF was generally well tolerated. The incidence of oral candidiasis was higher with FF 800 μg than placebo; pharmacokinetic and 24 h urinary cortisol analyses confirmed a higher systemic exposure of FF at this highest dose level.
Conclusions FF doses <800 μg have a favourable therapeutic index. The absence of an efficacy dose response suggests that 200 μg is an appropriate dose in patients with moderate persistent asthma.
ClinicalTrials.gov identifier NCT00603746.
- evening dosing
- fluticasone furoate
- fluticasone propionate
- inhaled corticosteroids
- once-daily dosing
- asthma epidemiology
- asthma genetics
- asthma pharmacology
- drug reactions
- asthma guidelines
- asthma in primary care
- COPD mechanisms
- COPD epidemiology
- inhaler devices
- COPD pathology
- eosinophil biology
- exhaled airway markers
- allergic lung disease
Funding This study was funded by GlaxoSmithKline (study number FFA109684). Editorial support in the form of development of the draft outline, development of the manuscript first draft, editorial suggestions to draft versions of this paper, assembling tables and figures, collating author comments, copyediting, fact checking, referencing and graphic services was provided by Geoff Weller at Gardiner-Caldwell Communications and was funded by GlaxoSmithKline. The colour print publication fee was paid by GlaxoSmithKline.
Competing interests WWB has served as a consultant to AstraZeneca, Boehringer Ingelheim, Novartis and TEVA; served on advisory boards for Altair, Amgen, Centocor, GlaxoSmithKline, Johnson & Johnson, Merck Sharpe and Dohme and Pfizer; received lecture fees from Merck Sharpe and Dohme; and received research funding from AstraZeneca, Ception, GlaxoSmithKline, MedImmune and Novartis. ERB has served as a consultant to GlaxoSmithKline; and has performed clinical trials for GlaxoSmithKline, which have been administered by his employer Wake Forest University Health Sciences. EDB has served as a consultant to and received lecture fees from GlaxoSmithKline; and his institution has received remuneration for participation in clinical trials sponsored by GlaxoSmithKline. JL has served as a consultant to and received lecture fees from AstraZeneca, GlaxoSmithKline, Merck Sharpe and Dohme, Novartis and UCB Pharma; has been partly covered by some of these companies to attend previous scientific meetings including the ERS and the AAAAI; and has participated in clinical research studies sponsored by AstraZeneca, GlaxoSmithKline, Merck Sharpe and Dohme, and Novartis. RF, AMD, LJ and BH are employees of and hold stock in GlaxoSmithKline. AW has served as consultant to Almirall, AstraZeneca, Chiesi, GlaxoSmithKline, Merck Sharpe and Dohme, Novartis and Schering Plough; and has received research grants and travel expenses for attendance at ATS and ERS meetings from GlaxoSmithKline.
Ethics approval IRB ethics committee for each centre.
Provenance and peer review Not commissioned; externally peer reviewed.