The effect of umeclidinium on lung function and symptoms in patients with fixed airflow obstruction and reversibility to salbutamol: A randomised, 3-phase study

Abstract

Introduction: The long-acting muscarinic antagonist, umeclidinium (UMEC), combined with the inhaled corticosteroid, fluticasone furoate (FF), improves lung function in symptomatic patients with asthma. We assessed FF/UMEC in patients with a primary diagnosis of asthma or chronic obstructive pulmonary disease (COPD), but physiological characteristics of both (fixed airflow obstruction and reversibility to salbutamol).

Methods: This double-blind, parallel-arm, 3-phase study randomised 338 patients (1:1:1:1:2:2) to FF 100 mcg alone or combined with UMEC (15.6, 62.5, 125, or 250 mcg) or vilanterol 25 mcg (Phase A, 4 weeks). Primary endpoint: change from baseline in clinic trough forced expiratory volume in 1 s (FEV₁) (end of Phase A). Secondary endpoints: morning peak expiratory flow (PEF), rescue medication use and Evaluating Respiratory Symptoms in COPD (E-RS™: COPD) scores. Safety was assessed.

Results: In the intent-to-treat population, the increase in trough FEV₁ over FF was significant for FF/UMEC 62.5 (0.140 L [p = 0.019]) and 125 mcg (0.120 L [p = 0.039]), with similar changes for patients with a primary diagnosis of asthma or COPD. Changes from baseline in morning PEF and E-RS total score were greater for all FF/UMEC doses vs FF (p ≤ 0.05). Change from baseline in rescue medication use was statistically or clinically significant for all FF/UMEC doses vs FF. The incidence of on-treatment adverse events was 15%-32% (Phase A), with no dose-related effects.

Conclusions: FF/UMEC 62.5 mcg produced clinically meaningful improvements in FEV₁, morning PEF, E-RS total score and rescue medication use. FF/UMEC may benefit patients with features of both asthma and COPD. CLINICALTRIALS.GOV: NCT02164539; GSK: 200699.

Keywords: Asthma; Chronic obstructive pulmonary disease; Inhaled corticosteroids; Long-acting muscarinic antagonist; Umeclidinium.