SESSION TITLE: Late-Breaking Abstracts
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Tuesday, October 28, 2014 at 08:45 AM - 10:00 AM
PURPOSE: Umeclidinium (UMEC) is a long-acting muscarinic antagonist approved in the US and EU for maintenance treatment of chronic obstructive pulmonary disease (COPD). Fluticasone furoate/vilanterol (FF/VI; combination inhaled corticosteroid [ICS] + long-acting beta2 agonist [LABA]) is indicated for long-term, once-daily maintenance treatment of airflow obstruction in COPD. These two replicate studies evaluated efficacy and safety of UMEC added to FF/VI in patients with COPD.
METHODS: These were 12-week, randomized, double-blind, parallel-group studies (N=1238 [intent-to-treat population]). Eligible patients entered a 4-week run-in period on FF/VI (100/25 mcg; delivering 92 and 22 mcg, respectively) and were then randomized 1:1:1 to once-daily blinded UMEC 62.5 mcg (delivering 55 mcg), UMEC 125 mcg (delivering 113 mcg), or placebo (PBO) added to open-label FF/VI if they met randomization criteria. Primary endpoint was trough forced expiratory volume in one second (FEV1) on Day 85. Secondary endpoint was 0-6-hour post-dose weighted mean (WM) FEV1 on Day 84. Rescue use was also assessed. Safety endpoints included incidence of on-treatment adverse events (AEs) and AEs of special interest.
RESULTS: Compared with PBO+FF/VI, both doses of UMEC+FF/VI in both studies produced statistically significant and clinically meaningful improvements in trough FEV1 at Day 85 (range: 0.111-0.128 L, all p<0.001) and 0-6-hour WM FEV1 at Day 84 (range: 0.135-0.153 L, all p<0.001). Over Weeks 1-12, mean change from baseline in percentage rescue-free days was greater for UMEC 62.5+FF/VI (6.9-14.2%) and UMEC 125+FF/VI (5.9-8.7%) compared with PBO+FF/VI (2.3-3.8%). Reduction in puffs/day was significantly greater for UMEC 62.5+FF/VI compared with PBO+FF/VI (p≤0.003). Incidence of any on-treatment AEs were similar across all groups in both studies (30-39%). Fewer on-treatment cardiovascular AEs of special interest were reported with UMEC+FF/VI compared with PBO+FF/VI (≤1-2% vs 3%). Six deaths occurred (PBO+FF/VI [n=5]; UMEC 62.5+FF/VI [n=1]); none were considered related to study drug.
CONCLUSIONS: Once-daily UMEC (62.5 or 125 mcg) added to once-daily FF/VI resulted in improvements in lung function and rescue use compared with PBO+FF/VI in patients with COPD. Safety profiles were consistent across all treatment groups.
CLINICAL IMPLICATIONS: Triple combination therapy with UMEC+FF/VI is an effective treatment in patients with moderate-to-very-severe COPD. Studies were funded by GlaxoSmithKline (200109; NCT01957163; 200110; NCT02119286).
DISCLOSURE: Thomas Siler: Consultant fee, speaker bureau, advisory committee, etc.: "AZ - Speaker, advisory board BI - Speaker UCB - Speaker Novartis - Speaker", Grant monies (from industry related sources): "Boehringer-Ingelheim - research support Daiichi-Sankyo - research support Elevation - research support Forest Research Institute - research support GlaxoSmithKline - research support Novartis - research support Pearl Therapeutics - research support Sepracor - research support Sunovion - research support", Consultant fee, speaker bureau, advisory committee, etc.: Vapotherm - Consulting Edward Kerwin: Grant monies (from industry related sources): Multicenter clinical trials performed for over 70 pharmaceutical companies, including GlaxoSmithKline., Consultant fee, speaker bureau, advisory committee, etc.: I have served on advisory boards, speaker panels, or received travel reimbursement for Amphastar, Astra Zeneca, Forest, Ironwood, Merck, Mylan, Novartis, Pearl, Pfizer, Sanofi Aventis, Sunovion, Targacept, Teva and Theravance. Alison Donald: Employee: GlaxoSmithKline The following authors have nothing to disclose: Ana Sousa, Rehan Ali, Alison Church
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