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

FF/UMEC 62.5 mcg produced clinically meaningful improvements in FEV, 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.

A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids

“…With a sample size of 115 patients per treatment group, the study had 80% power to detect a statistically significant difference in trough FEV 1 at Week 24 at the 2-sided 5% level, assuming a true treatment difference of 130 mL and standard deviation (SD) of 350 mL [8,15]. Randomisation of 128 patients per treatment group was planned to allow 10% missing data.…”

“…The benefits of the LAMA umeclidinium (UMEC) on lung function are well established in chronic obstructive pulmonary disease (COPD) [13], and have also been described in patients with asthma and in those with features of both asthma and COPD [14,15]. For example, improvements in trough forced expiratory volume in 1 s (FEV 1 ) and pre-dose peak expiratory flow (PEF) have been reported for UMEC in combination with the ICS fluticasone furoate (FF) versus FF alone [14,15]. To characterise the effects of UMEC in asthma and its longevity, this 24-week superiority study was conducted to evaluate the efficacy, safety and tolerability of once-daily UMEC 31.25 mcg or 62.5 mcg versus placebo in patients with asthma receiving FF 100 mcg who had previously been receiving ICS with or without a long-acting bronchodilator.…”

“…To characterise the effects of UMEC in asthma and its longevity, this 24-week superiority study was conducted to evaluate the efficacy, safety and tolerability of once-daily UMEC 31.25 mcg or 62.5 mcg versus placebo in patients with asthma receiving FF 100 mcg who had previously been receiving ICS with or without a long-acting bronchodilator. UMEC 62.5 mcg was chosen as the upper dose based on findings from a previous study in which clinically meaningful improvements in lung function were reported versus FF alone [15]. The 31.25 mcg dose was selected for our study because the lowest UMEC dose used in the previous study (15.6 mcg) showed only modest improvements in lung function.…”

“…The 31.25 mcg dose was selected for our study because the lowest UMEC dose used in the previous study (15.6 mcg) showed only modest improvements in lung function. Patients were required to have fully reversible asthma, with a postbronchodilator FEV 1 /forced vital capacity (FVC) ≥0.7 [2], in order to exclude patients with fixed airway obstruction, in whom UMEC dose selection has previously been explored [15]. This study forms part of a clinical development programme for a closed triple ICS/LAMA/LABA therapy for asthma and will be used to help inform the choice of UMEC dose in the target population for FF/UMEC/VI.…”

“…This study forms part of a clinical development programme for a closed triple ICS/LAMA/LABA therapy for asthma and will be used to help inform the choice of UMEC dose in the target population for FF/UMEC/VI. While the main focus of the study was to assess efficacy of UMEC on pulmonary function as measured by clinic and home spirometry, the Evaluating Respiratory Symptoms (E-RS) questionnaire [16,17] was also included to evaluate its utility in patients with asthma with milder disease than have been assessed in previous studies [14,15]. The E-RS is a respiratory symptom score developed and validated for use as part of the EXAcerbations of COPD (EXACT) instrument, a patient-reported outcome (PRO) measure for COPD, and subsequently evaluated in patients with features of both asthma and COPD [18].…”