Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI) and FF over 12 weeks in patients with persistent asthma Poster #407 Bernstein DI(1), Bateman ED(2), Woodcock A(3), Toler WT(4), Forth R(5), Jacques

Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI)

and FF over 12 weeks in patients with persistent asthma

Bernstein DI(1), Bateman ED(2), Woodcock A(3), Toler WT(4), Forth R(5), Jacques L(6), Nunn C(6), O Byrne PM(7)

(1)College of Medicine, University of Cincinnati, Cincinnati, OH, USA; (2)Department of Medicine, University of Cape Town, Cape Town, South Africa; (3)Institute of Inflammation and Repair, University of Manchester, Manchester, UK; (4)Respiratory Medicines Development Center, GlaxoSmithKline, RTP, NC, USA; (5)Quantitative Sciences Division, GlaxoSmithKline, RTP, NC, USA; (6)Respiratory Medicines Development Centre, GlaxoSmithKline, London, UK; (7)Michael G DeGroote School of Medicine, Hamilton, ON, Canada

Treatment guidelines for persistent asthma in patients not controlled with inhaled corticosteroid (ICS) therapy alone recommend an ICS with a long-acting beta2 agonist (LABA),(1) leading to improved lung function and asthma symptom control compared with ICS monotherapy.(2)

FF is an ICS in development as a once-daily (OD) monotherapy and available as a combination therapy with the LABA VI (FF/VI) for the treatment of COPD in the USA and for COPD and asthma in the EU and a number of other countries.(3),(4)

FF/VI 200/25mcg OD significantly improves lung function and symptomatic endpoints compared with FF alone,(5) while numeric benefits have been reported for FF/VI 100/25mcg compared with FF 100mcg.(6)

To compare the efficacy and safety of OD FF/VI 100/25mcg with FF 100mcg in patients with moderate-to-severe, persistent bronchial asthma over 12 weeks.

To assess the relative efficacy of FF/VI 100/25mcg with FF/VI 200/25mcg in these patients (descriptive comparison only).

Phase III, multicenter, randomized, double-blind, parallel-group study.

Patient inclusion criteria: >12 years of age; FEV1 40 80% predicted; demonstrated >12% and >200mL reversibility to albuterol; receiving ICS for >12 weeks pre-study and stable with a mid-to-high dose ICS or mid-dose ICS/LABA for 4 weeks pre-study.

Following a 4-week run-in without LABA, patients symptomatic or using rescue on >4 of the last 7 days of run-in were randomized 1:1:1 (stratified by baseline forced expiratory volume in one second [FEV1], <65% versus >65%) to FF 100mcg, FF/VI 100/25mcg or FF/VI 200/25mcg administered in the evening via the ELLIPTA dry powder inhaler OD for 12 weeks.

Primary and secondary endpoints were analyzed using ANCOVA (covariates of baseline, region, sex, age and treatment) with a step-down statistical hierarchy for FF 100mcg versus FF/VI 100/25mcg.

Of 2019 patients screened, 1039 were randomized and received at least one dose of study medication (intent-to-treat [ITT] population; Table 1), with 90% of patients completing the study.

Table 1. Baseline demographics (ITT population)

Values are mean (SD) unless otherwise stated. (a)n=342; (b)n=344; (c)n=346

There were statistically significant improvements with FF/VI 100/25mcg versus FF 100mcg for the primary endpoint of weighted mean 0 24h FEV1 (Figs. 1 2) and the secondary and other endpoints, except for AQLQ score (Fig. 1).

There were numerical improvements for all efficacy endpoints with FF/VI 200/25mcg versus FF/VI 100/25mcg (Fig. 3).

Figure 1. Adjusted treatment differences and ratios for efficacy

endpoints: FF/VI 100/25mcg versus FF 100mcg (ITT population)

ACT = Asthma Control Test ; AQLQ = Asthma Quality of Life Questionnaire; CI = confidence interval; PEF = peak expiratory flow; wm = weighted mean

Figure 2. Adjusted mean change from baseline of individual

serial FEV1 assessments at Week 12 (ITT population)

Figure 3. Adjusted treatment differences and ratios for efficacy

endpoints: FF/VI 200/25mcg versus 100/25mcg (ITT population)

Incidence of AEs and serious AEs (SAEs) were similar across treatments; there were no post-treatment SAEs and no fatal AEs.

Table 2. Summary of AE incidence and most commonly

reported on-treatment AEs (ITT population)

(a)investigator s judgement of causality; (b)includes on-treatment and post-treatment AEs;

(c)2 pneumonia, 1 borderline mucinous ovarian tumour; (d)biliary colic, acute pancreatitis, thermal burn, occipital neuralgia; (e)abortion threatened

There were statistically significant improvements in lung function and symptoms with FF/VI 100/25mcg versus FF 100mcg after 12 weeks of treatment in patients with moderate-to-severe persistent bronchial asthma.

Numerical improvements were seen for FF/VI 200/25mcg versus FF/VI 100/25mcg across all endpoints with patients on FF/VI 200/25mcg being 55% more likely to be well controlled than those on FF/VI 100/25mcg.

No new safety concerns were identified for any of the study treatments.

(1) Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention 2012. http://www.ginasthma.com/Guidelines/guidelines-resources.html (accessed 3/20/2014).

(2) Ducharme FM, et al. Cochrane Database Syst Rev 2010;10:CD005533.

(3) Breo Ellipta Medication Guide. Food and Drug Administration. www.fda.gov/downloads/drugs/drugsafety/ucm352347.pdf (accessed 4/08/2014).

(4) EPAR Summary For The Public. European Medicines Agency. www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/ 002673/WC500157636.pdf (accessed 4/08/2014).

(5) O Byrne PM, et al. Eur Respir J 2014;43:773 82.

(6) Bleecker ER, et al. J Allergy Clin Immunol Pract 2014; ePub ahead of print (25 April 2014).

The presenting author, WT Toler, is an employee of and holds stock in GlaxoSmithKline.

This study was funded by GlaxoSmithKline (HZA116863, NCT01686633).

Editorial support (in the form of writing assistance, assembling tables and figures, collating author comments, grammatical editing and referencing) was provided by David Cutler, PhD at Gardiner-Caldwell Communications (Macclesfield, UK) and was funded by GlaxoSmithKline.

ELLIPTA is a trade mark of GlaxoSmithKline

Presented at the American Thoracic Society Annual Congress, San Diego, CA, USA, 16 21 May 2014