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Efficacy and safety of umeclidinium/vilanterol (UMEC/VI) once daily (OD) vs fluticasone/salmeterol (FSC) combination twice daily (BD) in patients with moderate-to-severe COPD and infrequent COPD exacerbations James F. Donohue, MD, FCCP Department of Medicine, University of North Carolina, North Carolina, USA Presentation No: 73A Disclosures Jim Donohue has the following statement of interest: served as consultant to Almirall, AstraZeneca, Boehringer Ingelheim, Elevation Pharmaceuticals, Forest Laboratories, GSK, Mylan, Novartis, Pearl Pharmaceuticals, Pfizer and Sunovion served as a member of Drug Safety Monitoring Boards for the NIH, Novartis, Otsuka, Pearl and Teva Off-label discussion declaration I will not be discussing off-label uses of the treatments presented here Primary objective To compare the efficacy and safety of once-daily UMEC/VI 62.5/25mcg with twice-daily FSC 250/50mcg over 12 weeks in patients with moderate-to-severe COPD with a history of infrequent COPD exacerbations Two studies were conducted DB2114930 (NCT01817764) DB2114951 (NCT01879410) COPD: chronic obstructive pulmonary disease; FSC: fluticasone propionate/salmeterol; UMEC: umeclidinium; VI: vilanterol Study design * delivered doses 55/22mcg via ELLIPTA dry powder inhaler ** via DISKUS inhaler Week 4 Day 1 Pre-screen Screen Week 8 Week 12 Day 84 primary endpoint Day 85 secondary endpoint Follow-up Run-in FSC 250/50mcg twice daily** 7 14 days 12-week treatment period 7 2 days UMEC/VI 62.5/25mcg once daily* Key inclusion and exclusion criteria Inclusion males or females 40 years old with moderate-to-severe COPD post-salbutamol FEV1 30% and 70% predicted normal dyspnea score 2 (mMRC Dyspnea Scale) Exclusion documented history of 1 COPD exacerbation requiring oral corticosteroids, antibiotics and/or hospitalization in the year prior to screening FEV1: forced expiratory volume in 1s; mMRC: modified Medical Research Council an=353 for UMEC/VI and FSC groups; bn=349 (UMEC/VI) and 348 (FSC); cmean (standard deviation); dn=696; en=704; fn=704 in DB2114930; gmedian (range) Key baseline demographics and disease characteristics (ITT) DB2114930 (N=706)a DB2114951 (N=697)b Age, yearsc 62.8 (8.97) 63.6 (8.55) Males, n (%) 497 (70) 528 (76) Current smoker, n (%) 304 (43) 363 (52) Pre-salbutamol FEV1, Lc 1.322 (0.4312) 1.335 (0.4530)d Post-salbutamol FEV1, Lc 1.451 (0.4440)e 1.488 (0.4603) GOLD stage (% predicted FEV1)f Stage II Stage III 347 (49) 357 (51) 346 (50) 351 (50) Reversible to salbutamol, n (%) 189 (27)e 239 (34)d mMRC dyspnea scale scoreg 2.0 (2 4) 2.0 (2 4) ITT: intent-to-treat UMEC/VI demonstrated greater improvements in 024h wmFEV1 than FSC on day 84 (primary endpoint) aLS mean change (SE) from baseline on day 84; btreatment difference (95% confidence interval) LS: least-squares; SE: standard error; wm: weighted mean 0.0 0.1 0.2 0.3 0.4 UMEC/VI 62.5/25mcg FSC 250/50mcg 0.074 (0.038, 0.110) b p 0.001 0.165 (0.0130) n=315 DB2114930 DB2114951 Change from baseline in 0 24h wmFEV 1 (L) a 0.091 (0.0131) n=310 0.213 (0.0137) n=322 0.112 (0.0139) n=311 0.101 (0.063, 0.139) b p 0.001 UMEC/VI demonstrated greater improvements in trough FEV1 than FSC on day 85 (secondary endpoint) aLS mean change (SE) from baseline on day 85; btreatment difference (95% confidence interval) 0.0 0.1 0.2 0.3 UMEC/VI 62.5/25mcg FSC 250/50mcg 0.082 (0.045, 0.119) b p 0.001 0.154 (0.0133) n=317 DB2114930 DB2114951 Change from baseline in trough FEV 1 (L) a 0.072 (0.0134) n=312 0.185 (0.0138) n=323 0.087 (0.0140) n=311 0.098 (0.059, 0.137) b p 0.001 UMEC/VI demonstrated greater improvements in serial FEV1 than FSC on day 84 Statistically significant improvements with UMEC/VI versus FSC were seen at each time point on day 84 in both studies except at 18h* in DB2114930 (p=0.107) CI: confidence interval 0.00 0.05 0.10 0.15 0.20 0.25 0.30 UMEC/VI 62.5/25mcg FSC 250/50mcg 0 6 12 18 24 DB2114930 * Time (hours) LS mean (95% CI) change from baseline (L) 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 UM