Kerwin,Edward M, Kalberg,Chris J, Galkin,Dmitry V, Zhu,Chang-Qing, Church,Alison, Riley,John H, Fahy,William A, Kerwin,Edward M, Kalberg,Chris J, Galkin,Dmitry V, Zhu,Chang-Qing, Church,Alison, Riley,John H, and Fahy,William A
Edward M Kerwin,1 Chris J Kalberg,2 Dmitry V Galkin,2 Chang-Qing Zhu,3 Alison Church,2 John H Riley,4 William A Fahy4 1Clinical Research Institute of Southern Oregon, Medford, OR, 2Respiratory Department, GlaxoSmithKline, Research Triangle Park, NC, USA; 3Clinical Statistics, GlaxoSmithKline, Stockley Park, Uxbridge, Middlesex, 4Respiratory Department, GlaxoSmithKline, Stockley Park, Uxbridge, Middlesex, UK Introduction: Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO). Methods: In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%–70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks. Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0–3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). Safety evaluations included adverse events (AEs). Results: Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45–131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27–72]; P<0.001). Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: -0.1 puffs/d [95% CI: -0.2–0.0]; P≤0.0