A randomized, blinded study to evaluate the efficacy and safety of umeclidinium 62.5 μg compared with tiotropium 18 μg in patients with COPD

Abstract

Background

The long-acting muscarinic antagonists umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD. This study investigated the efficacy and safety of UMEC versus TIO in COPD.

Methods

This was a 12-week, multicenter, randomized, blinded, double-dummy, parallel-group, non-inferiority study. Patients were randomized 1:1 to UMEC 62.5 μg plus placebo or TIO 18 μg plus placebo. The primary end point was trough forced expiratory volume in 1 second (FEV₁) at day 85 (non-inferiority margin −50 mL; per-protocol [PP] population). Other end points included weighted mean FEV₁ over 0–24 and 12–24 hours post-dose. Patient-reported outcomes comprised Transition Dyspnea Index score, St George’s Respiratory Questionnaire total score, and COPD Assessment Test score. Adverse events were also assessed.

Results

In total, 1,017 patients were randomized to treatment. In the PP population, 489 and 487 patients received UMEC and TIO, respectively. In the PP population, change from baseline in trough FEV₁ was greater with UMEC versus TIO at day 85, meeting non-inferiority and superiority margins (difference: 59 mL; 95% confidence interval [CI]: 29–88; P<0.001). Similar results were observed in the intent-to-treat analysis of trough FEV₁ at day 85 (53 mL, 95% CI: 25–81; P<0.001). Improvements in weighted mean FEV₁ over 0–24 hours post-dose at day 84 were similar with UMEC and TIO but significantly greater with UMEC versus TIO over 12–24 hours post-dose (70 mL; P=0.015). Clinically meaningful improvements in Transition Dyspnea Index and St George’s Respiratory Questionnaire were observed with both treatments at all time points. No differences were observed between UMEC and TIO in patient-reported outcomes. Overall incidences of adverse events were similar for UMEC and TIO.

Conclusion

UMEC 62.5 μg demonstrated superior efficacy to TIO 18 μg on the primary end point of trough FEV₁ at day 85. Safety profiles were similar for both treatments.

Keywords:

• tiotropium
• umeclidinium
• COPD
• non-inferiority
• long-acting muscarinic antagonist

Acknowledgments

This study was funded and conducted by GSK (GSK study number: 201316; Clinicaltrials.gov identifier: NCT2207829). Palvi Shah (GSK Clinical Statistics, Stockley Park, UK) provided substantial contributions to the study data analysis, data interpretation, and preparation of the manuscript. Medical writing assistance was provided by Stuart Wakelin and Matthew Robinson of Fishawack Indicia Ltd (UK), funded by GSK.

Disclosure

GF has no conflicts of interest in this work. FM holds a CIHR/GSK research chair on COPD and has received fees for speaking at conferences sponsored by Boehringer Ingelheim (BI), Novartis, and Grifols, and has served on advisory boards for GSK and BI. He has also received research grants from GSK, BI, AstraZeneca, Nycomed, and Novartis, and has received an unrestricted research grant from BI and GSK. SK, MVB, AC, and WAF are employees of GSK and hold stocks/shares in GSK. RT was an employee of GSK and holder of stock/shares in GSK at the time of the study but is now employed by Pearl Therapeutics. The authors report no other conflicts of interest in this work.