Abstract
Combinations of drugs with distinct and complementary mechanisms of action may offer improved efficacy in the treatment of chronic obstructive pulmonary disease (COPD). In two 12-week, double-blind, parallel-group studies, patients with COPD were randomized 1:1:1 to once-daily umeclidinium (UMEC; 62.5 μg and 125 μg) or placebo (PBO), added to twice-daily fluticasone propionate/salmeterol (FP/SAL; 250/50 μg). In both studies, the primary efficacy measure was trough forced expiratory volume in 1 second (FEV1) at Day 85. Secondary endpoints were weighted-mean (WM) FEV1 over 0–6 hours post-dose (Day 84) and rescue albuterol use. Health-related quality of life outcomes (St. George's Respiratory Questionnaire [SGRQ] and COPD assessment test [CAT]) were also examined. Safety was assessed throughout. Both UMEC+FP/SAL doses provided statistically significant improvements in trough FEV1 (Day 85: 0.127–0.148 L) versus PBO+FP/SAL. Similarly, both UMEC+FP/SAL doses provided statistically-significant improvements in 0–6 hours post-dose WM FEV1 versus PBO+FP/SAL (Day 84: 0.144–0.165 L). Rescue use over Weeks 1–12 decreased with UMEC+FP/SAL in both studies versus PBO+FP/SAL (Study 1, 0.3 puffs/day [both doses]; Study 2, 0.5 puffs/day [UMEC 125+FP/SAL]). Decreases from baseline in CAT score were generally larger for both doses of UMEC+FP/SAL versus PBO+FP/SAL (except for Day 84 Study 2). In Study 1, no differences in SGRQ score were observed between UMEC+FP/SAL and PBO+FP/SAL; however, in Study 2, statistically significant improvements were observed with UMEC 62.5+FP/SAL (Day 28) and UMEC 125+FP/SAL (Days 28 and 84) versus PBO+FP/SAL. The incidence of on-treatment adverse events across all treatment groups was 37–41% in Study 1 and 36–38% in Study 2. Overall, these data indicate that the combination of UMEC+FP/SAL can provide additional benefits over FP/SAL alone in patients with COPD.
Highlights
Inhaled anti-inflammatory agents and bronchodilators such as corticosteroids, muscarinic antagonists and β2-agonists are central to the pharmacological management of chronic obstructive pulmonary disease (COPD) [1,2]
Patient demographics and characteristics were well balanced between treatment groups and between studies, except the proportion of females in Study 2 was lower for UMEC 62.5 μg + Fluticasone propionate plus salmeterol (FP/SAL) compared with the other treatment groups (Table 1) and there were more current smokers in Study 1 (50−57%) than in Study 2 (36−39%)
Outcomes Lung function In both studies, treatment with either dose of UMEC (62.5 μg or 125 μg) + FP/SAL resulted in statistically significant and clinically-meaningful mean improvements of 0.127–0.148 L in trough forced expiratory volume in 1 second (FEV1) at Day 85 compared with PBO + FP/SAL
Summary
Inhaled anti-inflammatory agents and bronchodilators such as corticosteroids, muscarinic antagonists and β2-agonists are central to the pharmacological management of chronic obstructive pulmonary disease (COPD) [1,2]. Clinical studies have shown the use of an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination together with a longacting muscarinic antagonist (LAMA) is well tolerated in patients with COPD and associated with improvements in lung function, symptoms, and health status compared with individual ICS/LABA or LAMA therapy [3,4,5]. These findings are reflected in the current version of Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, which recommend the combined use of an ICS/LABA product with a LAMA as a secondary treatment option for symptomatic patients with severe airflow obstruction and at high risk of exacerbations [2]. To fully characterize the efficacy and safety profile of UMEC, two doses of UMEC (62.5 and 125 μg) were investigated in subsequent studies
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