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

Respiratory Research, Apr 2016

Background Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose–response, efficacy, and safety of once-daily VI (6.25 μg, 12.5 μg and 25 μg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS. Methods This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5–11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 μg twice daily. Children were randomised to receive placebo, VI 6.25 μg, VI 12.5 μg or VI 25 μg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV 1 ) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations. Results In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV 1 was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28–33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period. Conclusion VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed. Trial registration NCT01573767 (ClinicalTrials.gov).

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

Oliver et al. Respiratory Research Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy Amanda J. Oliver 0 Ronina A. Covar 2 Caroline H. Goldfrad 0 Ryan M. Klein 1 Søren E. Pedersen 6 Christine A. Sorkness 5 Susan A. Tomkins 0 César Villarán 4 Jonathan Grigg 3 0 GlaxoSmithKline , Stockley Park West, 1 − 3 Iron Bridge Road, Uxbridge, Middlesex UB11 1BT , UK 1 Southern California Clinical Trials , Newport Beach, CA , USA 2 Department of Pediatrics, National Jewish Health , Denver, CO , USA 3 Blizard Institute, Queen Mary University London , London , UK 4 Clinica Ricardo Palma, Javier Prado Este 1166 San Isidro , Lima , Perú 5 University of Wisconsin School of Medicine and Public Health , Madison, WI , USA 6 University of Southern Denmark, Pediatric Research Unit, Kolding Hospital , Kolding , Denmark Background: Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose-response, efficacy, and safety of once-daily VI (6.25 μg, 12.5 μg and 25 μg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS. Methods: This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5-11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 μg twice daily. Children were randomised to receive placebo, VI 6.25 μg, VI 12.5 μg or VI 25 μg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV1) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations. Results: In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV1 was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28-33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period. Conclusion: VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed. Trial registration: NCT01573767 (ClinicalTrials.gov). Asthma; Children; Dose response; Efficacy; Fluticasone propionate; Safety; Vilanterol Background Asthma is common in children and is a leading cause of childhood hospitalisation [ 1 ]. National and international guidelines advocate the use of inhaled long-acting beta-2 agonists (LABA) in combination with inhaled corticosteroids (ICS) as maintenance therapy for children ages 5–11 years who remain symptomatic despite medium doses of ICS [ 2, 3 ]. A network meta-analysis including over 12,000 patients across 35 studies found that combined ICS/LABA treatments were more effective than low-dose ICS in preventing asthma exacerbations among paediatric patients [4]. In addition, studies indicate that the addition of LABA to a low dose of ICS can provide benefits such as improved asthma control in some children compared with increasing the ICS dose [ 5 ] and a reduced impact on growth by 1.2 cm/year compared with double the dose of ICS [ 6 ]. Despite the availability of effective therapies, many children with asthma remain uncontrolled, with low adherence proposed as a potential contributing factor [ 7, 8 ]. In addition, studies in adult and adolescent patients using dry powder inhalers for treatment of asthma and chronic obstructive pulmonary disease have shown that adherence with a once-daily regimen is greater than with a twicedaily regimen [ 9, 10 ]. However, currently available ICS/ LABA combination therapies require a twice-daily regimen [ 11, 12 ]. Vilanterol (VI) is a potent, inhaled LABA which, in combination with the ICS fluticasone furoate (FF), has been approved for the treatment of asthma in adults and adolescents in the EU, and in adults in the US [ 13–15 ]. In preclinical in vitro studie (...truncated)


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Amanda Oliver, Ronina Covar, Caroline Goldfrad, Ryan Klein, Søren Pedersen, Christine Sorkness, Susan Tomkins, César Villarán, Jonathan Grigg. Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy, Respiratory Research, 2016, pp. 37, 17, DOI: 10.1186/s12931-016-0353-4