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Respir Res. 2018 Jul 13;19(1):133. doi: 10.1186/s12931-018-0836-6.

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

Author information

1
Medical Research Institute of New Zealand, Private Bag 7902, Newtown, Wellington, 6242, New Zealand.
2
Respiratory Clinical Development, GlaxoSmithKline Research and Development, Stockley Park, Uxbridge, UK.
3
Medicines Development Centre, GlaxoSmithKline Research and Development, Stevenage, UK.
4
GlaxoSmithKline Research and Development, 82 Hughes Ave, Ermington, NSW, 2115, Australia.
5
Quantitative sciences, GlaxoSmithKline, Bangalore, India.
6
Medical Research Institute of New Zealand, Private Bag 7902, Newtown, Wellington, 6242, New Zealand. james.fingleton@mrinz.ac.nz.

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

PMID:
30001712
PMCID:
PMC6044077
DOI:
10.1186/s12931-018-0836-6
[Indexed for MEDLINE]
Free PMC Article

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