Safety, tolerability, pharmacokinetics, and pharmacodynamics of vilanterol, a novel inhaled long‐acting β‐agonist, in children aged 5–11 years with persistent asthma: A randomized trial

Abstract

This multi-center, randomized, double-blind, placebo-controlled, two-way crossover study was designed to characterize the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of single and once-daily repeat doses of vilanterol 25 µg in children aged 5–11 years. Twenty-eight children with persistent asthma received a single inhaled dose of vilanterol 25 µg or placebo via the ELLIPTA™ dry powder inhaler (DPI) on Day 1, followed 7 days later by once-daily treatment for 7 days. Nine (33%) subjects reported adverse events (AEs) with vilanterol 25 µg and 6 (23%) with placebo. No serious or drug-related AEs were reported; 3 subjects experienced upper respiratory tract infection (URTI) with vilanterol 25 µg versus none with placebo. Similar pharmacokinetic profiles of vilanterol 25 µg were observed irrespective of age or gender. No clinically relevant changes in heart rate, Fridericia's correction (QTcF), maximum glucose or minimum potassium parameters were observed during treatment with vilanterol 25 µg compared with placebo treatment. Vilanterol was well-tolerated and no long-acting ß2-agonist (LABA)-mediated AEs were observed. The pharmacokinetic profile of vilanterol 25 µg suggests exposure is similar regardless of age or gender in a pediatric population aged 5–11 years.

Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy

“…At the two lower doses of VI, the majority of PK samples were below quantifiable levels. The mean plasma concentration of VI 10−15 min post-dose was dose-ordered and systemic exposure observed for VI 25 μg was similar to that observed in a Phase IIa study of FF/VI 100/25 μg in children [ 18 ]. As only one post-dose blood sample was collected, conclusions on maximum plasma concentration (C max ) and time to maximum plasma concentration (t max ) cannot be drawn from this study.…”

“…At 10−15 min post-dose, the proportion of samples below the LLQ was 48, 30 and 20 % for the VI 6.25, VI 12.5 and VI 25 groups, respectively. The concentration-time data for the current study were combined with data from previous studies conducted in children with asthma receiving either VI 25 μg alone [ 18 ] or in combination with FF [ 17 ]. The mean plasma concentrations of VI 10−15 min post-dose were dose ordered and as expected for the doses administered (17.27 pg/mL, 40.04 pg/mL and 90.47 pg/mL, after treatment with VI 6.25 μg, VI 12.5 μg and VI 25 μg, respectively).…”

“…As only one post-dose blood sample was collected, conclusions on maximum plasma concentration (C max ) and time to maximum plasma concentration (t max ) cannot be drawn from this study. However, studies in adults suggest that VI 25 μg is rapidly absorbed and eliminated from the systemic circulation [ 28 , 29 ] and in children VI 25 μg has been shown to reach a C max shortly after dosing (t max of 12 min) [ 18 ].…”

Pharmacology and Therapeutics of Bronchodilators Revisited

“…In effect, the systemic exposure to formoterol for children versus adults is almost doubled and that for adolescents is about 30% higher compared with adults; both correlate inversely with age and body size (Chawes et al, 2014). Nevertheless, the lack of relationship between once-a-day vilanterol exposure and age or sex in pediatric asthma subjects aged 5-11 years inadequately controlled on an ICS has been documented, suggesting that a single dose may be suitable for this population; however, the study did not show any significant increase in trough FEV 1 from baseline with any of the vilanterol doses examined (Oliver et al, 2014) and there are very few studies investigating the use of vilanterol in pediatric patients (Dwan et al, 2016).…”

The combination of fluticasone furoate and vilanterol trifenatate in the management of asthma: clinical trial evidence and experience

“…Doses greater than or equal to 12.5 μg of inhaled VI daily appeared to be needed to achieve a bronchodilator effect in patients with asthma [Lotvall et al 2012]. The pharmacokinetics of VI 25 μg daily was consistent in children aged 5–11 years regardless of age or sex [Oliver et al 2014b]. No significant safety issues were uncovered with inhaled VI in these trials.…”