Once-daily fluticasone furoate alone or combined with vilanterol in persistent asthma

Abstract

The inhaled corticosteroid fluticasone furoate (FF) and the long-acting β₂ agonist vilanterol (VI) are in development as a combined once-daily therapy for asthma and chronic obstructive pulmonary disease. Our study objectives were to compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily fluticasone propionate (FP) in patients aged ≥12 years with moderate-to-severe persistent asthma. Patients (n=586) received FF/VI 200/25 μg or FF 200 μg once-daily (evening dosing), or FP 500 μg twice-daily for 24 weeks. Co-primary end-points were change from baseline in trough forced expiratory volume in 1 s (FEV₁) weighted mean (wm) 0-24 h serial FEV1. Secondary end-points included change from baseline in percentage of rescue-free 24-h periods, percentage of symptom-free 24-h periods and total Asthma Quality of Life Questionnaire (AQLQ). Safety assessments included adverse events, 24-h urinary cortisol excretion, vital signs and ECG. FF/VI significantly improved trough FEV1 and wmFEV₁ versus FF and FP. Significantly more rescue-free and symptom-free 24-h periods were reported with FF/VI versus FF. Treatment differences for AQLQ were not significant. Incidence of adverse events was similar across groups. No clinically significant differences were seen for 24-h urinary cortisol excretion, vital signs or ECG. FF/VI resulted in statistically greater improvements in lung function and symptomatic end-points versus FF, and was well tolerated in this asthma population.

Trial registration: ClinicalTrials.gov NCT01134042.

Figure 1–

Consort/patient flow diagram. FF: fluticasone furoate; FP: fluticasone propionate; ITT: intent-to-treat; VI: vilanterol. ^#: one patient was randomised to the FP 500 μg group in error, but did not receive study drug and was thus not included in the ITT population.

Figure 2–

Repeated measures analysis for the primary end-point of change from baseline in trough forced expiratory volume in 1 s over 24 weeks of treatment (intent-to-treat population). Data are presented as least squares mean (95% CI). FF: fluticasone furoate; VI: vilanterol; FP: fluticasone propionate.

Figure 3–

Adjusted mean change from baseline of individual serial forced expiratory volume in 1 s assessments following 24 weeks of treatment (intent-to-treat population). Data are presented as least squares mean (95% CI). FF: fluticasone furoate; VI: vilanterol; FP: fluticasone propionate.

Figure 4–

Cumulative incidence curves for withdrawals due to lack of efficacy over the 24-week treatment period (intent-to-treat population). FF: fluticasone furoate; VI: vilanterol; FP: fluticasone propionate.