The effect of umeclidinium on lung function and symptoms in patients with fixed airflow obstruction and reversibility to salbutamol: A randomised, 3-phase study. (October 2017)

• Record Type: Journal Article
• Authors: Lee, Laurie; Kerwin, Edward; Collison, Kathryn; Nelsen, Linda; Wu, Wei; Yang, Shuying; Pascoe, Steven
• Is Part Of: Respiratory medicine. Volume 131(2017)
• Page Start: 148
• Page End: 157
• Publication Date: 2017-10
• Subjects: Asthma -- Chronic obstructive pulmonary disease -- Inhaled corticosteroids -- Long-acting muscarinic antagonist -- Umeclidinium; AE adverse event -- AESI AEs of special interest -- ANCOVA analysis of covariance -- CI confidence interval -- COPD chronic obstructive pulmonary disease -- ECG electrocardiogram -- E-RS™: COPD Evaluating Respiratory Symptoms in COPD -- FEV1 forced expiratory volume in 1 s -- FF fluticasone furoate -- FP/SAL fluticasone propionate/salmeterol -- FVC forced vital capacity -- ICS inhaled corticosteroids -- ITT intent-to-treat -- LABA long-acting β-antagonist -- LAMA long-acting muscarinic receptor antagonist -- LS least squares -- MCID minimal clinically important difference -- PEF peak expiratory flow -- SAEs serious AEs -- SGRQ St George's Respiratory Questionnaire -- UMEC umeclidinium -- VI vilanterol; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2017.08.013
• Languages: English
• ISSNs: 0954-6111

Abstract

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. Highlights: FF/UMEC 100/62.5 and 100/125 mcg improved lung function in patients with features of both asthma and COPD. Improved morning peak expiratory flow, E-RS total score, SGRQ scores and rescue medication use supported dose selection. Adverse events were 15%–32% in Phase A, with no dose-related effects. FF/UMEC 100/62.5 mcg may benefit patients with fixed airflow obstruction and reversibility to salbutamol.