PMID- 27028749 OWN - NLM STAT- MEDLINE DCOM- 20170501 LR - 20220310 IS - 1179-6901 (Electronic) IS - 1174-5886 (Print) IS - 1174-5886 (Linking) VI - 16 IP - 2 DP - 2016 Jun TI - Dual Bronchodilator Therapy with Umeclidinium/Vilanterol Versus Tiotropium plus Indacaterol in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial. PG - 217-27 LID - 10.1007/s40268-016-0131-2 [doi] AB - INTRODUCTION: The fixed-dose, long-acting bronchodilator combination of umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a combination of a long-acting muscarinic antagonist and long-acting beta2-agonist in patients with chronic obstructive pulmonary disease (COPD). METHODS: This 12-week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg + indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD. The primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85 (predefined non-inferiority margin -50 mL), and the secondary endpoint was the 0- to 6-h weighted mean (WM) FEV1 on day 84. Other efficacy endpoints [including rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the St. George's Respiratory Questionnaire (SGRQ) score] and safety endpoints [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed. RESULTS: Trough FEV1 improvements were comparable between treatment groups [least squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171 mL; treatment difference 1 mL; 95 % confidence interval (CI) -29 to 30 mL], demonstrating non-inferiority between UMEC/VI and TIO + IND. The treatments produced similar improvements in the trough FEV1 at other study visits and the 0- to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL; treatment difference -23 mL; 95 % CI -54 to 8 mL). The results for patient-reported measures (rescue medication use, TDI focal score, and SGRQ score) were comparable; both treatments produced clinically meaningful improvements in TDI and SGRQ scores. The incidence of AEs and COPD exacerbations, and changes in vital signs were similar for the two treatments. CONCLUSION: UMEC/VI and TIO + IND, given once daily, provided similar improvements in lung function and patient-reported outcomes over 12 weeks in patients with COPD, with comparable tolerability and safety profiles. TRIAL NUMBERS: ClinicalTrials.gov study ID NCT02257385; GSK study no. 116961. FAU - Kalberg, Chris AU - Kalberg C AD - GSK, PO Box 13398, Research Triangle Park, NC, 27709-3398, USA. chris.j.kalberg@gsk.com. FAU - O'Dell, Dianne AU - O'Dell D AD - GSK, PO Box 13398, Research Triangle Park, NC, 27709-3398, USA. FAU - Galkin, Dmitry AU - Galkin D AD - GSK, PO Box 13398, Research Triangle Park, NC, 27709-3398, USA. FAU - Newlands, Amy AU - Newlands A AD - Respiratory Medicines Development Centre, GSK, Stockley Park, Middlesex, UK. FAU - Fahy, William A AU - Fahy WA AD - Respiratory Medicines Development Centre, GSK, Stockley Park, Middlesex, UK. LA - eng SI - ClinicalTrials.gov/NCT02257385 PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PL - New Zealand TA - Drugs R D JT - Drugs in R&D JID - 100883647 RN - 0 (Benzyl Alcohols) RN - 0 (Bronchodilator Agents) RN - 0 (Chlorobenzenes) RN - 0 (Drug Combinations) RN - 0 (GSK573719) RN - 0 (Indans) RN - 0 (Muscarinic Antagonists) RN - 0 (Quinolones) RN - 0 (Quinuclidines) RN - 028LZY775B (vilanterol) RN - 8OR09251MQ (indacaterol) RN - XX112XZP0J (Tiotropium Bromide) SB - IM MH - Administration, Inhalation MH - Adult MH - Aged MH - Aged, 80 and over MH - Benzyl Alcohols/administration & dosage/*therapeutic use MH - Bronchodilator Agents/administration & dosage/*therapeutic use MH - Chlorobenzenes/administration & dosage/*therapeutic use MH - Double-Blind Method MH - Drug Combinations MH - Female MH - Forced Expiratory Volume/drug effects MH - Humans MH - Indans/administration & dosage/*therapeutic use MH - Male MH - Middle Aged MH - Muscarinic Antagonists/administration & dosage/*therapeutic use MH - Pulmonary Disease, Chronic Obstructive/*drug therapy MH - Quinolones/administration & dosage/*therapeutic use MH - Quinuclidines/administration & dosage/*therapeutic use MH - Tiotropium Bromide/administration & dosage/*therapeutic use MH - Treatment Outcome PMC - PMC4875926 EDAT- 2016/03/31 06:00 MHDA- 2017/05/02 06:00 PMCR- 2016/03/30 CRDT- 2016/03/31 06:00 PHST- 2016/03/31 06:00 [entrez] PHST- 2016/03/31 06:00 [pubmed] PHST- 2017/05/02 06:00 [medline] PHST- 2016/03/30 00:00 [pmc-release] AID - 10.1007/s40268-016-0131-2 [pii] AID - 131 [pii] AID - 10.1007/s40268-016-0131-2 [doi] PST - ppublish SO - Drugs R D. 2016 Jun;16(2):217-27. doi: 10.1007/s40268-016-0131-2.