Efficacy and safety of umeclidinium added to fluticasone furoate/vilanterol in chronic obstructive pulmonary disease: Results of two randomized studies

• Published in: Respiratory medicine Vol. 109; no. 9; pp. 1155 - 1163
• Main Authors: Siler, Thomas M., Kerwin, Edward, Sousa, Ana R., Donald, Alison, Ali, Rehan, Church, Alison
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2015; Elsevier Limited
• Subjects: Adrenergic beta-2 Receptor Agonists - adverse effects; Adrenergic beta-2 Receptor Agonists - therapeutic use; Aged; Androstadienes - adverse effects; Androstadienes - therapeutic use; Benzyl Alcohols - adverse effects; Benzyl Alcohols - therapeutic use; Bronchodilation; Chlorobenzenes - adverse effects; Chlorobenzenes - therapeutic use; Chronic obstructive pulmonary disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug dosages; Drug Therapy, Combination; Female; Forced Expiratory Volume - drug effects; Glucocorticoids - adverse effects; Glucocorticoids - therapeutic use; Humans; Inhaled corticosteroid; Long-acting beta2 agonist; Long-acting muscarinic antagonist; Male; Middle Aged; Mortality; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - adverse effects; Muscarinic Antagonists - therapeutic use; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary/Respiratory; Quality of Life; Quinuclidines - administration & dosage; Quinuclidines - adverse effects; Quinuclidines - therapeutic use; Respiratory diseases; Studies; Vital Capacity - drug effects; FF; GOLD; LS; ITT; PRO; QoL; UMEC; ASE; WM; LABA; HRQoL; PBO; Bronchodilation; AE; Long-acting muscarinic antagonist; MedDRA; CI; Inhaled corticosteroid; LAMA; FVC; VI; SGRQ; SAE; CAT; RI; ICS; FEV1; Long-acting beta2 agonist; COPD; umeclidinium; forced vital capacity; run-in; vilanterol; patient-reported outcome; placebo; fluticasone furoate; St George's Respiratory Questionnaire; adverse event; health-related quality of life; FEV 1; weighted mean; least squares; quality of life; Global Initiative for Chronic Obstructive Lung Disease; intent-to-treat; Medical Dictionary for Regulatory Activities; serious adverse event; COPD Assessment Test; all subjects enrolled; Long-acting beta 2 agonist; forced expiratory volume in one second; confidence interval; chronic obstructive pulmonary disease; Long-acting beta agonist
• ISSN: 0954-6111; 1532-3064; 1532-3064
• DOI: 10.1016/j.rmed.2015.06.006

The aim of these studies (NCT01957163; NCT02119286) was to evaluate the efficacy and safety of umeclidinium (UMEC 62.5 μg and 125 μg) added to fluticasone furoate/vilanterol (FF/VI, 100/25 μg) in chronic obstructive pulmonary disease (COPD). These were 12-week, double-blind, placebo-controlled, parallel-group, multicenter studies. Eligible patients were randomized 1:1:1 to treatment with once-daily blinded UMEC 62.5 μg (delivering 55 μg), UMEC 125 μg (delivering 113 μg) or placebo (PBO) added to open-label FF/VI (delivering 92/22 μg; N = 1238 [intent-to-treat population]). The primary endpoint was trough forced expiratory volume in one second (FEV1) on Day 85; the secondary endpoint was 0–6 h post-dose weighted mean (WM) FEV1 at Day 84. Health-related quality of life was reported using St George's respiratory questionnaire (SGRQ). Adverse events (AEs) were also assessed. In both studies, trough FEV1 was significantly improved with UMEC + FF/VI (62.5 μg and 125 μg) versus PBO + FF/VI (range: 0.111–0.128 L, all p < 0.001 [Day 85]), as was 0–6 h post-dose WM FEV1 (range: 0.135–0.153 L, all p < 0.001 [Day 84]). SGRQ results were inconsistent, with statistically significant improvements with UMEC + FF/VI versus PBO + FF/VI in one study only and with UMEC 62.5 μg only (difference in SGRQ total score from baseline between treatments: −2.16, p < 0.05). Across all treatment groups, the overall incidences of AEs were similar (30–39%), as were cardiovascular AEs of special interest (<1–3%) and pneumonia AEs (0–1%). Overall, the addition of UMEC to FF/VI therapy resulted in significant improvements in lung function compared with PBO + FF/VI in patients with COPD, with similar safety profiles, though SGRQ results were inconsistent. The results from these two studies demonstrate that the addition of umeclidinium (62.5 μg and 125 μg) to FF/VI (100/25 μg) provides statistically significant and clinically meaningful improvements in lung function compared with placebo + FF/VI in patients with COPD. Statistically significant improvements in quality of life with UMEC + FF/VI versus placebo + FF/VI were reported in one study only. Safety profiles were consistent across all treatment groups in both studies. These studies support the use of triple therapy in COPD, providing physicians with an alternative treatment option. •Umeclidinium (UMEC) is a long-acting muscarinic antagonist indicated for the treatment of COPD.•Fluticasone furoate/vilanterol (FF/VI) is a corticosteroid/long acting beta agonist for COPD.•These data show that triple therapy with UMEC + FF/VI significantly improves lung function vs FF/VI.•Safety profiles were consistent across all treatment groups in both studies.