Efficacy and safety of once-daily inhaled umeclidinium/vilanterol in Asian patients with COPD: results from a randomized, placebo-controlled study

Abstract

Background: Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU. We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.

Patients and methods: In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo. The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1. Additional end points and safety were also assessed.

Results: Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001). Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016). On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001). Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001). The incidence of adverse events was similar across groups.

Conclusion: In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo. Symptomatic and quality of life measures also improved. The safety profile of UMEC/VI was consistent with previous studies.

Keywords: Asian; chronic obstructive pulmonary disease; umeclidinium; vilanterol.

Figure 1

Patient disposition. Abbreviations: AEs, adverse events; ECG, electrocardiogram; UMEC, umeclidinium; VI, vilanterol.

Figure 2

LS mean change from baseline in trough FEV₁ up to day 169 (ITT population). Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; ITT, intent-to-treat; LS, least squares; UMEC, umeclidinium; VI, vilanterol.

Figure 3

LS mean change from baseline in serial FEV₁ on day 1 (ITT population). Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; ITT, intent-to-treat; LS, least squares; UMEC, umeclidinium; VI, vilanterol.

Figure 4

LS mean TDI focal score (ITT population). Abbreviations: CI, confidence interval; ITT, intent-to-treat; LS, least squares; TDI, Transition Dyspnea Index; UMEC, umeclidinium; VI, vilanterol.