P124 A randomised, parallel-group study to evaluate the effect of umeclidinium added to inhaled corticosteroid/long-acting beta-agonist combination therapy in subjects with chronic obstructive pulmonary disease

• Published in: Thorax Vol. 70; no. Suppl 3; p. A137
• Main Authors: Sousa, AR, Riley, JH, Church, A, Zhu, CQ, Punekar, YS, Fahy, WA
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.12.2015
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thoraxjnl-2015-207770.261

RationaleTo evaluate efficacy and safety of adding umeclidinium (UMEC), a long-acting muscarinic antagonist (LAMA), to inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) for 12-weeks.MethodsMulticentre, randomised, double-blind, parallel-group study. Inclusion criteria included diagnosis of COPD, modified Medical Research Council Dyspnoea Scale score ≥2 (i.e. patients symptomatic on ICS/LABA), post-salbutamol forced expiratory volume in one second (FEV1) ≤70% predicted and FEV1/forced vital capacity ratio of 1 at Day 85; other endpoints included 0−6 h weighted mean FEV1, rescue medication use, COPD assessment test (CAT) score, and transition dyspnoea index (TDI) score. Adverse events (AEs) were also investigated.ResultsIn the UMEC+ICS/LABA and PBO+ICS/LABA groups, 119 and 117 patients were randomised, respectively, receiving fluticasone/salmeterol (40%), budesonide/formoterol (43%), and other ICS/LABA, including generics (17%). Compared with PBO+ICS/LABA, UMEC+ICS/LABA resulted in statistically significant improvements in change from baseline trough FEV1 at Day 85 and 0−6 h weighted mean FEV1 at Day 84 (Table 1). UMEC+ICS/LABA resulted in a statistically significant reduction in change from baseline mean puffs/day of rescue salbutamol over Weeks 1–12 versus PBO+ICS/LABA, but not for percentage of rescue-free days. Change from baseline in CAT score at Day 84 was statistically significantly different for UMEC+ICS/LABA versus PBO+ICS/LABA, but TDI score was not significantly different for UMEC+ICS/LABA versus PBO+ICS/LABA; the study was not powered for these endpoints. Incidence of AEs was similar with UMEC+ICS/LABA and PBO+ICS/LABA; n = 45 (38%) and n = 49 (42%), respectively. The most common AEs were nasopharyngitis (13–15%) and headache (3–7%).Abstract P124 Table 1Endpoint resultsUMEC + ICS/LABA(N=119)PBO + ICS/LABA(N=117)Treatment Diff. vs PBO(95% CI)Trough FEV1 at Day 85LS mean change from baseline, L (SE)n = 1090.090 (0.0183)n = 110-0.033 (0.0184)0.123a (0.071, 0.174)0–6 hours weighted mean FEV1 at Day 84LS mean change from baseline, L (SE)n = 1070.184 (0.0176)n = 1100.035 (0.0175)0.148a (0.099, 0.197) Rescue use (mean puffs/day)*LS mean change from baseline (SE)n = 119-0.53 (0.105)n = 116-0.15 (0.106)-0.38b (-0.67, -0.10)Rescue use (% rescue-free days)*,**Median (range) n = 11976.8(0, 100)n = 11662.9(0, 100)0c (0.0, 3.4)CAT score at Day 84LS mean change from baseline (SE)n = 110-0.37 (0.457)n = 1100.94 (0.457)-1.31b (-2.59, -0.04)TDI score at Day 84LS mean (SE)n = 1051.07 (0.197)n = 1090.67 (0.195)0.40 (-0.15, 0.95)ap<0.001; bp<0.05; cp = 0.640, non-parametric analysis; *use over 1–12 weeks; **non-parametric analysis of % rescue-free days was a post hoc analysis and replaced the pre-specified analysis (percentage rescue-free day datadid not satisfy normality assumptions for MMRM analysis); improvements in CAT scores are shown by negative changes.ConclusionsUMEC+ICS/LABA improved lung function and reduced rescue medication use (mean puffs/day) and CAT score in patients with COPD versus PBO+ICS/LABA. No additional safety concerns were identified with UMEC+ICS/LABA.Funded by GlaxoSmithKline (NCT02257372).COI StatementARS, JR, AC, WAF, CQZ and YSP are employees of GSK and hold stocks/shares in GSK.