TY - JOUR
T1 - Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy
T2 - An 8-week, randomised, placebo-controlled trial
AU - Busse, William W.
AU - Bleecker, Eugene R.
AU - Bateman, Eric D.
AU - Lötvall, Jan
AU - Forth, Richard
AU - Davis, Angela M.
AU - Jacques, Loretta
AU - Haumann, Brett
AU - Woodcock, Ashley
N1 - Funding Information:
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.
PY - 2012/1
Y1 - 2012/1
N2 - 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 mg have a favourable therapeutic index. The absence of an efficacy dose response suggests that 200 mg is an appropriate dose in patients with moderate persistent asthma. ClinicalTrials.gov identifier: NCT00603746.
AB - 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 mg have a favourable therapeutic index. The absence of an efficacy dose response suggests that 200 mg is an appropriate dose in patients with moderate persistent asthma. ClinicalTrials.gov identifier: NCT00603746.
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U2 - 10.1136/thoraxjnl-2011-200308
DO - 10.1136/thoraxjnl-2011-200308
M3 - Article
AN - SCOPUS:84855187266
SN - 0040-6376
VL - 67
SP - 35
EP - 41
JO - Thorax
JF - Thorax
IS - 1
ER -