A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD

Abstract

This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV₁) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV₁ over 0-24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: -50 mL) to glycopyrronium (trough FEV₁ at day 85 treatment difference: 24 mL, 95% confidence intervals: -5-54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37%) and glycopyrronium (36%). Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV₁ at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

FIGURE 1

Consolidated Standards of Reporting Trials (CONSORT) diagram of patients enrolled in the study. ^#: Two pre-screen/screen failures were erroneously randomised, one to each study arm. They were subsequently excluded from the intent-to-treat (ITT) population, as they did not receive a dose of study medication. A further patient was excluded from the ITT population due to a protocol deviation. UMEC: umeclidinium; GLYCO: glycopyrronium; 24H: subset of patients who completed 24-h spirometry on day 1 and day 84; COPD: chronic obstructive pulmonary disease.

FIGURE 2

Change from baseline in trough forced expiratory volume in 1 s (FEV₁) (per-protocol population). No inferences can be made from the above comparisons at days 2, 28, 56 and 84 as this was a lung-function endpoint and the superiority criterion at day 85 was not reached. Data are presented as least squares mean±95% CI. UMEC: umeclidinium; GLYCO: glycopyrronium.

FIGURE 3

The proportion of patients with a ≥100 mL increase in trough forced expiratory volume in 1 s (FEV₁) from baseline (intent-to-treat population, post hoc analysis). No inferences can be made from the above comparisons as this was a lung-function endpoint and the superiority criterion was not reached. GLYCO: glycopyrronium; UMEC: umeclidinium.