Anti-inflammatory duration of action of fluticasone furoate/vilanterol trifenatate in asthma: a cross-over randomised controlled trial

Abstract

Background: Fluticasone furoate/Vilanterol trifenatate (FF/VI) is an inhaled corticosteroid/long-acting beta-agonist combination with a prolonged bronchodilator duration of action. We characterised the time-course of onset and offset of airway anti-inflammatory action of FF/VI, as assessed by fraction of exhaled nitric oxide (FeNO), and compared this to the bronchodilator duration of action.

Methods: A single-centre, randomised, double-blind, placebo-controlled, two-period, crossover study was undertaken in 28 steroid-naïve adults with asthma. Participants with an FEV1 ≥ 60% predicted, reversible airway disease, and FeNO > 40 ppb received FF/VI 100/25 mcg or placebo once daily for 14 days. FeNO and peak expiratory flow were measured twice-daily during treatment and during a 21-day washout period. FEV1 was measured for five days from treatment cessation. The primary outcome measure was FeNO change from baseline ratio for 21 days following treatment cessation.

Results: In the 27 subjects who completed the study, median (range) baseline FeNO was 87 ppb (42-212). FF/VI 100/25 mcg reduced FeNO by day 3, ratio FF/VI versus placebo 0.72 (95% confidence interval 0.61-0.86) with the maximum reduction occurring at day 14, 0.32 (0.27-0.37). Following cessation of treatment FeNO remained suppressed for 18 days, ratio on day 18 0.77 (0.59-1.00), whereas improvements in FEV1 and peak flow were maintained for 3 to 4 days post-treatment.

Conclusions: The anti-inflammatory duration of action of FF/VI is consistent with the high glucocorticoid receptor affinity and long lung retention of fluticasone furoate. The anti-inflammatory effect of FF/VI was of greater duration than its bronchodilator effect in adults with mild asthma. Funding GlaxoSmithKline (201499).

Trial registration: Prospectively registered on ClinicalTrials.gov registry number NCT02712047 .

Keywords: Asthma; Clinical trial; Nitric oxide.

Conflict of interest statement

Ethics approval and consent to participate

Prospective ethics approval was obtained from the Health and Disability Ethics Committees, New Zealand (Reference 16/STH/13).

Consent for publication

Not applicable.

Competing interests

GB, MW and TM have no conflicts of interest to declare. IB has conducted research funded by GSK, Astra-Zeneca and Fisher & Paykel. JF has received support to attend educational meetings from AstraZeneca, Boehringer-Ingelheim, GSK, and Novartis, has conducted research funded by GSK, Astra-Zeneca and Fisher & Paykel, and has received honoraria for speaking from AstraZeneca, Boehringer-Ingelheim and Novartis. RB has participated in advisory boards for AstraZeneca, GlaxoSmithKline and Novartis; received research grants from AstraZeneca, Cephalon, Fisher & Paykel, Genentech, GlaxoSmithKline, Novartis and Sanofi Aventis, and received payment for lectures or support to attend meetings from AstraZeneca and GlaxoSmithKline AB, RK, PB and PDY are GSK employees and hold GSK shares. KR and SJ are GSK employees.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Study schematic. SABA, short-acting beta-agonist; FF/VI, fluticasone furoate / vilanterol; FeNO, fraction of exhaled nitric oxide; PEF, peak expiratory flow, FEV1, forced expiratory volume in one second

Fig. 2

Time-course of anti-inflammatory activity of FF/VI. Mean exhaled nitric oxide (ppb), during treatment and after cessation of treatment, plotted over time, for placebo (grey line) and FF/VI (black line). Error bars denote the standard error

Fig. 3

Time-course of bronchodilator activity of FF/VI. a: FEV1 change from baseline. b: PEF. Mean (a) FEV1 (L) after cessation of treatment and (b) Peak expiratory flow (L/min), during treatment and after cessation of treatment, plotted over time, for placebo (grey line) and FF/VI (black line). Error bars denote the standard error