@article{34234f6a5674482e95f7673117a500cf,
title = "Comparison of vilanterol, a novel long-acting beta2 agonist, with placebo and a salmeterol reference arm in asthma uncontrolled by inhaled corticosteroids",
abstract = "Background: Current maintenance therapies for asthma require twice-daily dosing. Vilanterol (VI) is a novel long-acting beta2 agonist, under development in combination with fluticasone furoate, a new inhaled corticosteroid (ICS). Findings from a previous 4-week study suggested that VI has inherent 24-hour activity and is therefore suitable for once-daily dosing. The study described here was a double-blind, double-dummy, randomised, placebo-controlled trial, the aim of which was to assess the efficacy of once-daily VI compared with placebo in patients with persistent asthma. The primary endpoint was change from baseline in 24-hour weighted mean forced expiratory volume in 1 second after 12 weeks of treatment vs. placebo. An active control arm received salmeterol (SAL) twice daily. All patients were maintained on a stable background dose of ICS. Results: Patients (n = 347) received VI, placebo or SAL (1:1:1). For the primary endpoint, substantial improvements in lung function were seen with VI (359 ml), SAL (283 ml) and placebo (289 ml). There were no statistically significant treatment differences between either the VI (70 ml, P = 0.244) or SAL (-6 ml, P = 0.926) groups and placebo. Both active treatments were well tolerated, with similarly low rates of treatment-related adverse events compared with placebo. No treatment-related serious adverse events occurred. Conclusions: This study failed to show a treatment difference between VI and placebo for the primary endpoint, in the presence of a placebo response of unforeseen magnitude. Because the placebo response was so large, it is not possible to draw meaningful conclusions from the data. The reason for this magnitude of effect is unclear but it may reflect increased compliance with the anti-inflammatory therapy regimen during the treatment period. Trial registration. NCT01181895 at ClinicalTrials.gov.",
keywords = "Asthma, Bronchodilators, Long-acting beta agonist, Lung function, Placebo response, Randomised trial, Salmeterol, Vilanterol",
author = "Jan L{\"o}tvall and Bateman, {Eric D.} and Busse, {William W.} and O'Byrne, {Paul M.} and Ashley Woodcock and Toler, {William T.} and Loretta Jacques and Caroline Goldfrad and Bleecker, {Eugene R.}",
note = "Funding Information: This study was funded by GlaxoSmithKline (study number B2C112060; ClinicalTrials.gov number NCT01181895). The sponsor did not place any restriction on authors about the statements made in the final paper. The study was approved by local ethics review committees, and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from each patient prior to the performance of any study-specific procedures. All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors thank all patients and investigators involved in the study. We wish to acknowledge Jessica Lim (Quantitative Sciences Division, GlaxoSmithKline) for her contribution to the statistical analysis. Editorial support (in the form of development of a draft outline in consultation with the authors, development of a manuscript first draft in consultation with the authors, editorial suggestions to draft versions of this paper, assembling tables and figures, collating author comments, copyediting, fact checking, referencing and graphic services) was provided by Ian Grieve at Gardiner-Caldwell Communications and was funded by GlaxoSmithKline. Journal fees were paid for by GlaxoSmithKline. Funding Information: JL has served as a consultant to and received lecture fees from AstraZeneca, GlaxoSmithKline, Merck Sharpe and Dohme, Novartis and UCB Pharma; has been partly covered by some of these companies to attend previous scientific meetings including the ERS and the AAAAI; has provided expert testimony for Barr Pharmaceuticals; and has participated in clinical research studies sponsored by AstraZeneca, GlaxoSmithKline, Merck Sharpe and Dohme, and Novartis. EDB has served as a consultant to AlkAbello, Almirall, Cephalon, Hoffman la Roche, ICON and MS Consulting Group; been on advisory boards for Almirall, AstraZeneca, Boehringer Ingelheim, Elevation Pharma, Forest, GlaxoSmithKline, Merck, Napp, Novartis and Nycomed; and received lecture fees from AlkAbello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer and Takeda; and his institution has received remuneration for participation in clinical trials sponsored by Actelion, Aeras, Almirall, AstraZeneca, Boehringer Ingelheim, Forest, GlaxoSmithKline, Hoffman La Roche, Merck, Novartis, Takeda and TEVA. WWB has served as a consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, MedImmune, Novartis and TEVA; served on advisory boards for Altair, Amgen, Centocor, GlaxoSmithKline, Johnson & Johnson, Merck Sharpe and Dohme, and Pfizer; received lecture fees from Merck Sharpe and Dohme; and received research funding from AstraZeneca, Ception, GlaxoSmithKline, MedImmune and Novartis. PMO{\textquoteright}B has served as a consultant to AstraZeneca, Almirall, Boehringer Ingelheim, GlaxoSmithKline and Merck; has served on advisory boards for AIM, Altair, Boehringer Ingelheim, GlaxoSmithKline, MedImmune and Merck; has received lecture fees from Chiesi; and has received research funding from Amgen, AstraZeneca, Asmacure, Genentech and Ono. AW has served as a consultant to Almirall, Chiesi, Cytos and GlaxoSmithKline; and has received lecture fees and research grants from GlaxoSmithKline. ERB has served as a consultant to AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Johnson and Johnson, and Merck; and has performed clinical trials for AstraZeneca, Boehringer Ingelheim, Cephalon, Forest, Genentech, GlaxoSmithKline, KalaBios, MedImmune, Novartis, and Sanofi-Aventis which have been administered by his employer Wake Forest University School of Medicine. LJ, WTT and CG are employees of and hold stock in GlaxoSmithKline.",
year = "2014",
month = jun,
day = "13",
doi = "10.1186/1477-5751-13-9",
language = "English (US)",
volume = "13",
journal = "Journal of Negative Results in BioMedicine",
issn = "1477-5751",
publisher = "BioMed Central",
number = "1",
}