Efficacy and Safety of Once-Daily Inhaled Umeclidinium in Asian Patients with COPD: Results from a Randomized, Placebo-Controlled Study

Nanshan Zhong; Jinping Zheng; Sang Haak Lee; David A Lipson; Xin Du; Shunquan Wu

doi:10.2147/COPD.S215011

Efficacy and Safety of Once-Daily Inhaled Umeclidinium in Asian Patients with COPD: Results from a Randomized, Placebo-Controlled Study

Int J Chron Obstruct Pulmon Dis. 2020 Apr 17:15:809-819. doi: 10.2147/COPD.S215011. eCollection 2020.

Authors

Nanshan Zhong¹, Jinping Zheng¹, Sang Haak Lee², David A Lipson³, Xin Du⁴, Shunquan Wu⁴

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Centre of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
² Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea.
³ GSK, Collegeville, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴ GSK, Shanghai, People's Republic of China.

Abstract

Purpose: Previous studies demonstrating efficacy and safety of once-daily umeclidinium (UMEC) in patients with chronic obstructive pulmonary disease (COPD) have included few Asian patients. This study evaluated efficacy and safety of UMEC 62.5 mcg versus placebo in Asian patients with COPD.

Patients and methods: A Phase III, randomized, double-blind, parallel-group study. Patients (aged ≥40 years with COPD, pre-, and post-albuterol forced expiratory volume in 1 s [FEV₁]/forced vital capacity ratio <0.70 and low risk of exacerbations) were randomized 2:1 to once-daily UMEC 62.5 mcg or placebo via the ELLIPTA inhaler for 24 weeks. Primary endpoint was change from baseline (CFB) in trough FEV₁ on Day 169. Secondary endpoints were weighted mean FEV₁ over 0-6 hrs post-dose on Day 1 and CFB in Transition Dyspnea Index (TDI) focal score on Day 168.

Results: A total of 306 patients were included in the modified intent-to-treat population (UMEC: 205; placebo: 101). UMEC versus placebo provided a statistically significant improvement in least squares (LS) mean trough FEV₁ between baseline and Day 169 (154 mL [95% confidence interval (CI): 113, 194]; p<0.001). A clinically meaningful difference of 125 mL in favor of UMEC (95% CI: 103, 147; p<0.001) was also seen in LS weighted mean FEV₁ 0-6 hrs post-dose on Day 1. A LS mean treatment difference in TDI focal score of 0.9 units in favor of UMEC was seen on Day 168 (95% CI: 0.3, 1.5; p=0.004). Incidence of on-treatment adverse events (AEs) was lower in the placebo (55%) versus UMEC arm (60%); non-fatal serious AEs, drug-related AEs, and AEs leading to withdrawal were similar with UMEC and placebo.

Conclusion: Once-daily UMEC 62.5 mcg resulted in statistically significant and clinically meaningful improvements in lung function and dyspnea, compared with placebo, in Asian patients with COPD, with no new safety concerns observed.

Keywords: Asia; Transition Dyspnea Index; chronic obstructive pulmonary disease; forced expiratory volume in 1 second; umeclidinium.

Publication types

Randomized Controlled Trial

MeSH terms

Administration, Inhalation
Benzyl Alcohols / therapeutic use
Bronchodilator Agents / therapeutic use
Chlorobenzenes / therapeutic use
Double-Blind Method
Forced Expiratory Volume
Humans
Muscarinic Antagonists / therapeutic use
Pulmonary Disease, Chronic Obstructive* / diagnosis
Pulmonary Disease, Chronic Obstructive* / drug therapy
Quinuclidines / therapeutic use
Treatment Outcome

Substances

Benzyl Alcohols
Bronchodilator Agents
Chlorobenzenes
GSK573719
Muscarinic Antagonists
Quinuclidines