24-h duration of the novel LABA vilanterol trifenatate in asthma patients treated with inhaled corticosteroids

Abstract

Current guidelines recommend adding a long-acting inhaled b 2 -agonist (LABA) to inhaled corticosteroids (ICS) in patients with uncontrolled asthma. This study evaluated the novel, once-daily LABA vilanterol trifenatate (VI) in asthma patients who remained symptomatic despite existing ICS therapy.The study involved a randomised, double-blind, placebo-controlled trial of VI (3, 6.25, 12.5, 25 and 50 mg), administered once daily in the evening by dry powder inhaler for 28 days, in asthma patients aged o12 yrs symptomatic on current ICS therapy. The primary end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV1); secondary end-points were weighted mean FEV1, peak expiratory flow (PEF), symptom-/rescue-free 24-h periods, and safety.A significant relationship was observed between VI dose and improvements in trough FEV1 (p50.037). Statistically significant increases in mean trough FEV1, relative to placebo, were documented for VI 12.5-50 mg (121-162 mL; pf0.016). Dose-related effects of VI were observed on weighted mean (0-24 h) FEV1, morning/evening PEF, and symptom-/rescue-free 24-h periods. All doses of VI were well tolerated with low incidences of recognised LABA-related adverse events (tremor 0-2%; palpitations 0-2%; glucose effects 0-1%; potassium effects 0-,1%).Once-daily VI 12.5-50 mg resulted in prolonged bronchodilation of at least 24 h with good tolerability in asthma patients receiving ICS. Based on the overall efficacy and adverse event profile from this study, the optimum dose of VI appears to be 25 mg.

Metabolism and Disposition of Vilanterol, a Long-Actingβ2-Adrenoceptor Agonist for Inhalation Use in Humans

“…Vilanterol, GW642444, or 4-[(1R)-2- [(6-{2-[(2,6-dichlorophenyl) methoxy]ethoxy}hexyl)amino]-1-hydroxyethyl]-2-(hydroxyl methyl) phenol, is a novel long-acting b 2 -agonist (LABA) with inherent 24-hour activity for once-daily clinical treatment of chronic obstructive pulmonary disease (COPD) and asthma in combination with the inhaled novel corticosteroid fluticasone furoate, also active for 24 hours (Hanania et al, 2012;Lotvall et al, 2012). This publication describes in vitro and clinical studies conducted to determine the metabolism and disposition of vilanterol in humans.…”

Fluticasone Furoate/Vilanterol: a Review of Its Use in Patients with Asthma

“…The LABA vilanterol is highly selective for b 2 -adrenoreceptors and has 24-h activity [13,14]. Activation of b 2 -adrenergic receptors by LABAs such as vilanterol leads to relaxation of bronchial smooth muscle cells, causing bronchodilation [15].…”

“…Results from dose-ranging trials showed that fluticasone furoate 100 or 200 lg and vilanterol 25 lg provided an optimal balance between therapeutic effect [improvement over baseline in pre-dose evening (trough) FEV 1 ] and tolerability in patients with various levels of asthma severity [14,[17][18][19][20]. Furthermore, fluticasone furoate 200 lg once daily was non-inferior to a 100 lg twice daily dosage on day 28 in improving trough FEV 1 [21] and there was no significant difference between vilanterol 12.5 lg once daily and 6.25 lg twice daily groups in 0-24 h weighted mean (wm) FEV 1 on day 7 [18], suggesting that both drugs are suitable for once-daily administration.…”

Efficacy and safety of long-acting beta-2-agonists

“…Ви лантерол быстро абсорбировался в плазму (медиана Т max через 10 мин), системное воздействие (в диа пазоне доз 2-100 мкг) усиливалось с увеличением дозы [35,36]. У больных с неконтролируемой БА при приеме вилантерола в дозе 12,5-50,0 мкг (оптималь ная доза 25 мкг) 1 раз в день в комбинации с иГКС в течение 28 дней отмечены длительная бронходила тация (в течение ≥ 24 ч) и хорошая переносимость (тремор 0-2 %, тахикардия 0-2 %) [37]. В исследова нии с участием взрослых пациентов с персистирую щей БА сравнивались 2 режима приема препарата (6,2 мкг 2 раза в сутки и 12,5 мкг 1 раз в сутки).…”