A randomized, parallel-group study to evaluate the efficacy of umeclidinium/vilanterol 62.5/25 μg on health-related quality of life in patients with COPD

Abstract

Background

The combination of the inhaled muscarinic antagonist umeclidinium (UMEC) with the long-acting β₂-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD). This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population.

Methods

This was a 12-week multicenter, randomized, double-blind, parallel-group, placebo-controlled study. Eligible patients were randomized 1:1 to receive once-daily UMEC/VI 62.5/25 μg (via ELLIPTA^® dry powder inhaler) or PBO for 12 weeks. The primary endpoint was St George’s Respiratory Questionnaire (SGRQ) total score at day 84. Secondary efficacy endpoints included rescue albuterol use (puffs/day) over weeks 1–12 and trough forced expiratory volume in 1 second on day 84. Adverse events were also assessed.

Results

A total of 496 patients were included in the intent-to-treat population in the UMEC/VI (n=248) and PBO (n=248) treatment groups. UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in SGRQ total score at day 84 versus PBO (difference between treatments in SGRQ total score change from baseline: −4.03 [95% confidence interval {CI}: −6.28, −1.79]; P<0.001). UMEC/VI 62.5/25 μg resulted in a statistically significant reduction in rescue albuterol use versus PBO (−0.7 puffs/day [95% CI: −1.1, −0.4]; P<0.001). UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in trough forced expiratory volume in 1 second on day 84 versus PBO (122 mL [95% CI: 71, 172]; P<0.001). The incidence of adverse events was similar between treatments (32% and 30% of patients in the UMEC/VI 62.5/25 μg and PBO groups, respectively).

Conclusion

The results of this study demonstrate that treatment with UMEC/VI 62.5/25 μg provides clinically important improvements in SGRQ and rescue medication use versus PBO in patients with moderate-to-very-severe COPD.

Keywords:

• COPD
• umeclidinium
• vilanterol
• health-related quality of life
• SGRQ
• long-acting bronchodilator

Supplementary materials

Statistical analysis

The sample size calculation used an estimate of residual standard deviation (SD) of 12.63 units, which was the value observed in a previous study evaluating umeclidinium/vilanterol (UMEC/VI) 62.5/25 μg and placebo (PBO).¹ With >211 patients per treatment arm, there was >99% power to detect a difference of 100 mL between treatments in trough forced expiratory volume in 1 second with an estimate of residual SD of 220 mL. The study was designed to have 93% power to detect a difference of one puff/day between UMEC/VI and PBO for mean rescue medication use, at the two-sided 5% significance level, using an estimate of residual SD of 3.01 puffs/day over weeks 1–12. These estimates of SD were based on mixed-effect model repeated measures and analysis of covariance analyses from a previous study evaluating UMEC/VI.¹ Data for subjects who withdrew prematurely from the study were not explicitly imputed. Hence, to account for an estimated 15% withdrawal rate, 248 patients were planned to be randomized to each of the treatment groups (496 in total).

Table S1 Excluded medications prior to visit 1

Reference

• DonohueJFMaleki-YazdiMRKilbrideSMehtaRKalbergCChurchAEfficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPDRespir Med2013107101538154623830094
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Acknowledgments

This study (GSK study number: 201211; Clinicaltrials. gov identifier: NCT2152605) was funded by GSK. 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 Joanne Ashworth and Matthew Robinson of Fishawack Indicia Ltd (UK), funding by GSK.

Disclosure

TMS is part of a speaker bureau for AstraZeneca and Boehringer Ingelheim, and has received research support from AstraZeneca, Boehringer Ingelheim, Forest Research Institute, GSK, Novartis, Pearl Therapeutics, Theravance and Sunovion. ACD, AC, and WAF are employees of GSK and hold stocks/shares in GSK. DO 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.