Efficacy and safety of fluticasone furoate/vilanterol compared with fluticasone propionate/salmeterol combination in adult and adolescent patients with persistent asthma: a randomized trial

Abstract

Background: The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on a medium dose of ICS.

Methods: In a randomized, double-blind, double-dummy, parallel group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment.

Results: Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (341 mL) and FP/SAL (377 mL); the adjusted mean treatment difference was not statistically significant (-37 mL; 95% CI, -88 to 15, P = 0.162). There were no differences between 0- to 4-h serial wmFEV1, trough FEV1, and asthma control and quality-of-life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs and no treatment-related serious adverse events.

Conclusions: The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified.

Trial registration: ClinicalTrials.gov NCT01147848.

Figure 1.

Consolidated Standards of Reporting Trials patient flow diagram. AE = adverse event; BD = twice daily; FF = fluticasone furoate; FP = fluticasone propionate; ITT = intention to treat; OD = once daily; SAL = salmeterol; VI = vilanterol. ^aMain reason was that patients did not meet inclusion/exclusion criteria (n = 613 [39%]). ^bMain reason was that patients did not meet continuation criteria (n = 103 [7%]).

Figure 2.

Adjusted means for 0- to 24-h serial weighted mean FEV₁ at week 24 (intention-to-treat population). LS = least squares. See Figure 1 legend for expansion of other abbreviations.

Figure 3.

Adjusted mean change from baseline in FEV₁ over time at week 24 for FF/VI dosed OD in the evening and FP/SAL dosed BD (intention-to-treat population). See Figure 1 and 2 legends for expansion of abbreviations.

Figure 4.

Adjusted ratios to baseline for 24-h urinary cortisol excretion at week 24 (urinary cortisol population). See Figure 1 and 2 legends for expansion of abbreviations.