Rationale To 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.

Methods Multicentre, 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.

Results In 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%).

Conclusions UMEC+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 Statement ARS, JR, AC, WAF, CQZ and YSP are employees of GSK and hold stocks/shares in GSK.