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Alison Church - One of the best experts on this subject based on the ideXlab platform.
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A randomized, parallel-group study to evaluate the efficacy of Umeclidinium/vilanterol 62.5/25 μg on health-related quality of life in patients with COPD
International journal of chronic obstructive pulmonary disease, 2016Co-Authors: Thomas Siler, Alison Church, Alison Donald, Dianne O'dell, William A. FahyAbstract:Background The combination of the inhaled muscarinic antagonist Umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD). This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population.
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a randomized parallel group study to evaluate the efficacy of Umeclidinium vilanterol 62 5 25 μg on health related quality of life in patients with copd
International Journal of Chronic Obstructive Pulmonary Disease, 2016Co-Authors: Thomas Siler, Alison Church, Alison Donald, Dianne Odell, William A. FahyAbstract:Background The combination of the inhaled muscarinic antagonist Umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD). This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population.
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A randomised, open-label study of Umeclidinium versus glycopyrronium in patients with COPD
ERJ open research, 2016Co-Authors: Tara Renae Rheault, Alison Church, Sanjeev Khindri, Mitra Vahdati-bolouri, William A. FahyAbstract:This study compared the efficacy and safety of once-daily Umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to Umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV 1 ) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV 1 over 0–24 h and patient-reported outcomes (transition dyspnoea index score and St George9s Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: −50 mL) to glycopyrronium (trough FEV 1 at day 85 treatment difference: 24 mL, 95% confidence intervals: −5–54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for Umeclidinium (37%) and glycopyrronium (36%). Once-daily Umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV 1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.
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A randomized, blinded study to evaluate the efficacy and safety of Umeclidinium 62.5 μg compared with tiotropium 18 μg in patients with COPD.
International journal of chronic obstructive pulmonary disease, 2016Co-Authors: Gregory Feldman, François Maltais, Alison Church, Sanjeev Khindri, Mitra Vahdati-bolouri, William A. Fahy, Roopa TrivediAbstract:Background The long-acting muscarinic antagonists Umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD. This study investigated the efficacy and safety of UMEC versus TIO in COPD.
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magnitude of Umeclidinium vilanterol lung function effect depends on monotherapy responses results from two randomised controlled trials
Respiratory Medicine, 2016Co-Authors: James F. Donohue, Sally Kilbride, Dave Singh, Clara Munzu, Alison ChurchAbstract:Abstract Purpose Dual therapy with bronchodilators of different pharmacological classes may produce greater lung function improvements than either drug alone. However, the relationship between a patient's response to monotherapy and response to dual bronchodilator therapy is currently unknown. We aimed to investigate whether dual therapy with Umeclidinium/vilanterol provides additional benefit over Umeclidinium or vilanterol monotherapy in patients with chronic obstructive pulmonary disease (COPD) identified as responsive (increase from baseline in forced expiratory volume in 1s [FEV 1 ] of ≥12% and ≥200 mL, Day 1) or non-responsive to monotherapy. Methods In two randomised, double-blind, three-way complete-block, cross-over studies (DB2116132 n = 207; DB2116133 n = 182; intent-to-treat), all patients (moderate-to-very severe COPD) were randomised to 1 of 6 sequences and received once-daily Umeclidinium 62.5mcg, vilanterol 25mcg, and Umeclidinium/vilanterol 62.5/25mcg (one treatment/14-day period; 10–14-day washout). Key endpoints were 0–6 h weighted mean FEV 1 (Day 14) and trough FEV 1 (Day 15). Adverse events, vital signs and COPD exacerbations were assessed. Pooled data are presented. Results Umeclidinium/vilanterol significantly (p ≤ 0.001, unless stated otherwise) increased 0–6 h weighted mean FEV 1 versus Umeclidinium in Umeclidinium-responders (+114 mL), versus vilanterol in vilanterol-responders (+92 mL) and versus Umeclidinium (+70 mL) and vilanterol (+62 mL) in non-responders. Improvements in trough FEV 1 occurred with Umeclidinium/vilanterol versus Umeclidinium in Umeclidinium-responders (+77 mL), versus vilanterol in vilanterol-responders (+86 mL), and versus Umeclidinium (+42 mL [p = 0.020]) and vilanterol (+58 mL) in non-responders. All treatments were well tolerated. Conclusions Once-daily Umeclidinium/vilanterol significantly improved lung function in patients with COPD, with quantitatively greater improvements in patients identified as responders to Umeclidinium and vilanterol monotherapy than non-responders.
Rashmi Mehta - One of the best experts on this subject based on the ideXlab platform.
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population pharmacokinetic analysis of fluticasone furoate Umeclidinium vilanterol via a single inhaler in patients with copd
The Journal of Clinical Pharmacology, 2018Co-Authors: Rashmi Mehta, Noushin Brealey, Eleni Pefani, Misba Beerahee, Helen Barnacle, Ruby Birk, Chang-qing Zhu, David A. LipsonAbstract:A population pharmacokinetic analysis was conducted from a subset of samples obtained from the Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy trial to characterize the pharmacokinetics of fluticasone furoate, Umeclidinium, and vilanterol in patients with symptomatic COPD following treatment with fluticason furoate-Umeclidinium-vilanterol combined in a single inhaler. This was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticason furoate-Umeclidinium-vilanterol, 100 μg/62.5 μg/25 μg; Ellipta inhaler) with twice-daily dual therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler). The analyses were conducted in a subset of 74 patients who received fluticason furoate-Umeclidinium-vilanterol and provided serial or sparse samples. Monte Carlo simulations and a model-based estimation approach both indicated that systemic drug concentrations of fluticasone furoate, Umeclidinium, and vilanterol after administration of fluticason furoate-Umeclidinium-vilanterol triple combination therapy from a single inhaler were within the ranges observed following administration of these drugs as monotherapy (fluticasone furoate, Umeclidinium, and vilanterol) or as dual-combination therapy (fluticasone furoate/vilanterol or Umeclidinium/vilanterol).
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Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium/Vilanterol via a Single Inhaler in Patients with COPD
Journal of clinical pharmacology, 2018Co-Authors: Rashmi Mehta, Noushin Brealey, Eleni Pefani, Misba Beerahee, Helen Barnacle, Ruby Birk, Chang-qing Zhu, David A. LipsonAbstract:A population pharmacokinetic analysis was conducted from a subset of samples obtained from the Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy trial to characterize the pharmacokinetics of fluticasone furoate, Umeclidinium, and vilanterol in patients with symptomatic COPD following treatment with fluticason furoate-Umeclidinium-vilanterol combined in a single inhaler. This was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticason furoate-Umeclidinium-vilanterol, 100 μg/62.5 μg/25 μg; Ellipta inhaler) with twice-daily dual therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler). The analyses were conducted in a subset of 74 patients who received fluticason furoate-Umeclidinium-vilanterol and provided serial or sparse samples. Monte Carlo simulations and a model-based estimation approach both indicated that systemic drug concentrations of fluticasone furoate, Umeclidinium, and vilanterol after administration of fluticason furoate-Umeclidinium-vilanterol triple combination therapy from a single inhaler were within the ranges observed following administration of these drugs as monotherapy (fluticasone furoate, Umeclidinium, and vilanterol) or as dual-combination therapy (fluticasone furoate/vilanterol or Umeclidinium/vilanterol).
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R&D, Bioanalytical Sciences and
2016Co-Authors: Rashmi Mehta, Dennis Kelleher, Andrew Preece, Glenn Crater, Stephen Hughes, Correspondence Rashmi MehtaAbstract:which permits unrestricted noncommercial use, provided the original work is properly cited. International Journal of COPD 2013:8 159–167 International Journal of COPD Effect of verapamil on systemic exposure and safety of Umeclidinium and vilanterol: a randomized and open-label stud
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RESEARCH ARTICLE Pharmacokinetics and Tolerability of Inhaled Umeclidinium and Vilanterol Alone and in Combination in Healthy Chinese Subjects: A Randomized, Open-Label, Crossover Trial
2016Co-Authors: Jingying Jia, Rashmi Mehta, Linda Luo, Kelly Dong, Jack Peng, Yan Ren, Annette GrossAbstract:Inhaled Umeclidinium (UMEC) and the combination of inhaled UMEC with vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary dis-ease in the US and EU. This was a randomized, open-label, three-period crossover, single-and repeat-dose study to assess the pharmacokinetics (PK), safety, and tolerability of in-haled UMEC/VI 62.5/25 μg (delivering 55/22 μg) and UMEC/VI 125/25 μg (delivering 113/ 22 μg) compared with their monotherapy components (UMEC 62.5 μg, UMEC 125 μg and
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Effect of severe renal impairment on Umeclidinium and Umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study
International journal of chronic obstructive pulmonary disease, 2014Co-Authors: Rashmi Mehta, Kelly Hardes, Andrew Preece, Lee Tombs, Noushin Brealey, Dennis KelleherAbstract:Background Umeclidinium and vilanterol, long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease, are primarily eliminated via the hepatic route; however, severe renal impairment may adversely affect some elimination pathways other than the kidney.
Lee Tombs - One of the best experts on this subject based on the ideXlab platform.
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Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.
Respiratory research, 2020Co-Authors: François Maltais, Lee Tombs, David A. Lipson, Leif Bjermer, Paul W Jones, Ian Naya, Chris Compton, Claus Vogelmeier, Isabelle Boucot, Edward KerwinAbstract:Background: Short-acting β2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. Methods: The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily Umeclidinium/vilanterol 62.5/25 μg, once-daily Umeclidinium 62.5 μg or twice-daily salmeterol 50 μg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. Results: At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with Umeclidinium/vilanterol versus Umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59–74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with Umeclidinium/vilanterol versus Umeclidinium were observed only in high SABA users (high: − 0.56 [p < 0.001]; low: − 0.10 [p = 0.132]). Similar findings were observed when comparing Umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with Umeclidinium/vilanterol versus Umeclidinium compared with baseline SABA use < 4 puffs/day. Conclusions: In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. Funding: GlaxoSmithKline (study number 201749 [NCT03034915]). (Less)
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efficacy of Umeclidinium vilanterol versus Umeclidinium and salmeterol monotherapies in symptomatic patients with copd not receiving inhaled corticosteroids the emax randomised trial
Respiratory Research, 2019Co-Authors: François Maltais, Lee Tombs, David A. Lipson, Leif Bjermer, Edward Kerwin, Paul W Jones, Michael L Watkins, Ian Naya, I Boucot, Chris ComptonAbstract:Prospective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease worsening/treatment failure in low exacerbation risk patients with chronic obstructive pulmonary disease (COPD) not receiving inhaled corticosteroids. The 24-week, double-blind, double-dummy, parallel-group Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised patients at low exacerbation risk not receiving inhaled corticosteroids, to Umeclidinium/vilanterol 62.5/25 μg once-daily, Umeclidinium 62.5 μg once-daily or salmeterol 50 μg twice-daily. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at Week 24. The study was also powered for the secondary endpoint of Transition Dyspnoea Index at Week 24. Other efficacy assessments included spirometry, symptoms, heath status and short-term disease worsening measured by the composite endpoint of clinically important deterioration using three definitions. Change from baseline in trough FEV1 at Week 24 was 66 mL (95% confidence interval [CI]: 43, 89) and 141 mL (95% CI: 118, 164) greater with Umeclidinium/vilanterol versus Umeclidinium and salmeterol, respectively (both p < 0.001). Umeclidinium/vilanterol demonstrated consistent improvements in Transition Dyspnoea Index versus both monotherapies at Week 24 (vs Umeclidinium: 0.37 [95% CI: 0.06, 0.68], p = 0.018; vs salmeterol: 0.45 [95% CI: 0.15, 0.76], p = 0.004) and all other symptom measures at all time points. Regardless of the clinically important deterioration definition considered, Umeclidinium/vilanterol significantly reduced the risk of a first clinically important deterioration compared with Umeclidinium (by 16–25% [p < 0.01]) and salmeterol (by 26–41% [p < 0.001]). Safety profiles were similar between treatments. Umeclidinium/vilanterol consistently provides early and sustained improvements in lung function and symptoms and reduces the risk of deterioration/treatment failure versus Umeclidinium or salmeterol in symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids. These findings suggest a potential for early use of dual bronchodilators to help optimise therapy in this patient group.
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Efficacy of Umeclidinium/vilanterol versus Umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial
Respiratory research, 2019Co-Authors: François Maltais, Lee Tombs, David A. Lipson, Leif Bjermer, Edward Kerwin, Paul W Jones, Michael L Watkins, Ian Naya, Isabelle Boucot, Chris ComptonAbstract:Prospective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease worsening/treatment failure in low exacerbation risk patients with chronic obstructive pulmonary disease (COPD) not receiving inhaled corticosteroids. The 24-week, double-blind, double-dummy, parallel-group Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised patients at low exacerbation risk not receiving inhaled corticosteroids, to Umeclidinium/vilanterol 62.5/25 μg once-daily, Umeclidinium 62.5 μg once-daily or salmeterol 50 μg twice-daily. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at Week 24. The study was also powered for the secondary endpoint of Transition Dyspnoea Index at Week 24. Other efficacy assessments included spirometry, symptoms, heath status and short-term disease worsening measured by the composite endpoint of clinically important deterioration using three definitions. Change from baseline in trough FEV1 at Week 24 was 66 mL (95% confidence interval [CI]: 43, 89) and 141 mL (95% CI: 118, 164) greater with Umeclidinium/vilanterol versus Umeclidinium and salmeterol, respectively (both p
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Efficacy of Umeclidinium/Vilanterol in Elderly Patients with COPD: A Pooled Analysis of Randomized Controlled Trials
Drugs & Aging, 2018Co-Authors: Riju Ray, Lee Tombs, David A. Lipson, Chris Compton, Isabelle Boucot, Michael J. Asmus, Ian NayaAbstract:Objective The aim of this pooled analysis was to assess the efficacy and safety of Umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg dual bronchodilation versus placebo in elderly symptomatic patients with chronic obstructive pulmonary disease (COPD). Methods We conducted a post hoc pooled analysis of data from 10 randomized controlled trials (RCTs). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV_1), proportion of FEV_1 responders (≥ 100-mL increase from baseline), and safety were analyzed in patients aged
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Efficacy of Umeclidinium/Vilanterol in Elderly Patients with COPD: A Pooled Analysis of Randomized Controlled Trials.
Drugs & aging, 2018Co-Authors: Riju Ray, Lee Tombs, David A. Lipson, Chris Compton, Isabelle Boucot, Michael J. Asmus, Ian NayaAbstract:The aim of this pooled analysis was to assess the efficacy and safety of Umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg dual bronchodilation versus placebo in elderly symptomatic patients with chronic obstructive pulmonary disease (COPD). We conducted a post hoc pooled analysis of data from 10 randomized controlled trials (RCTs). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), proportion of FEV1 responders (≥ 100-mL increase from baseline), and safety were analyzed in patients aged
William A. Fahy - One of the best experts on this subject based on the ideXlab platform.
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Prevention of clinically important deteriorations in COPD with Umeclidinium/vilanterol
International journal of chronic obstructive pulmonary disease, 2016Co-Authors: Dave Singh, Lee Tombs, William A. Fahy, M. Reza Maleki-yazdi, Ahmar Iqbal, Ian NayaAbstract:Background Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis. We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD. The objective was to determine whether dual bronchodilation with Umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.
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prevention of clinically important deteriorations in copd with Umeclidinium vilanterol
International Journal of Chronic Obstructive Pulmonary Disease, 2016Co-Authors: Dave Singh, Lee Tombs, William A. Fahy, Ahmar Iqbal, Reza M Malekiyazdi, Ian NayaAbstract:Background Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis. We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD. The objective was to determine whether dual bronchodilation with Umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.
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Triple Therapy of Umeclidinium + Inhaled Corticosteroids/Long-Acting Beta_2 Agonists for Patients with COPD: Pooled Results of Randomized Placebo-Controlled Trials
Pulmonary Therapy, 2016Co-Authors: Thomas M. Siler, Lee Tombs, Edward Kerwin, William A. Fahy, Ian NayaAbstract:Introduction Data on triple therapy (long-acting muscarinic antagonist [LAMA] + inhaled corticosteroid/long-acting beta_2-agonist [ICS/LABA]) in symptomatic patients with chronic obstructive pulmonary disease (COPD) are limited. This post hoc analysis aimed to determine the efficacy of once-daily Umeclidinium (UMEC; 62.5 μg) or placebo (PBO) plus open-label fixed-dose ICS/LABA in symptomatic patients with COPD. Methods Data were pooled from four randomized, double-blind, parallel-group trials (ClincalTrials.gov identifiers: NCT01772134, NCT01772147, NCT01957163, NCT02119286). Inclusion criteria included COPD diagnosis, modified Medical Research Council dyspnea scale score ≥2 and forced expiratory volume in 1 s (FEV_1)
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A randomized, parallel-group study to evaluate the efficacy of Umeclidinium/vilanterol 62.5/25 μg on health-related quality of life in patients with COPD
International journal of chronic obstructive pulmonary disease, 2016Co-Authors: Thomas Siler, Alison Church, Alison Donald, Dianne O'dell, William A. FahyAbstract:Background The combination of the inhaled muscarinic antagonist Umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD). This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population.
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a randomized parallel group study to evaluate the efficacy of Umeclidinium vilanterol 62 5 25 μg on health related quality of life in patients with copd
International Journal of Chronic Obstructive Pulmonary Disease, 2016Co-Authors: Thomas Siler, Alison Church, Alison Donald, Dianne Odell, William A. FahyAbstract:Background The combination of the inhaled muscarinic antagonist Umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD). This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population.
James F. Donohue - One of the best experts on this subject based on the ideXlab platform.
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magnitude of Umeclidinium vilanterol lung function effect depends on monotherapy responses results from two randomised controlled trials
Respiratory Medicine, 2016Co-Authors: James F. Donohue, Sally Kilbride, Dave Singh, Clara Munzu, Alison ChurchAbstract:Abstract Purpose Dual therapy with bronchodilators of different pharmacological classes may produce greater lung function improvements than either drug alone. However, the relationship between a patient's response to monotherapy and response to dual bronchodilator therapy is currently unknown. We aimed to investigate whether dual therapy with Umeclidinium/vilanterol provides additional benefit over Umeclidinium or vilanterol monotherapy in patients with chronic obstructive pulmonary disease (COPD) identified as responsive (increase from baseline in forced expiratory volume in 1s [FEV 1 ] of ≥12% and ≥200 mL, Day 1) or non-responsive to monotherapy. Methods In two randomised, double-blind, three-way complete-block, cross-over studies (DB2116132 n = 207; DB2116133 n = 182; intent-to-treat), all patients (moderate-to-very severe COPD) were randomised to 1 of 6 sequences and received once-daily Umeclidinium 62.5mcg, vilanterol 25mcg, and Umeclidinium/vilanterol 62.5/25mcg (one treatment/14-day period; 10–14-day washout). Key endpoints were 0–6 h weighted mean FEV 1 (Day 14) and trough FEV 1 (Day 15). Adverse events, vital signs and COPD exacerbations were assessed. Pooled data are presented. Results Umeclidinium/vilanterol significantly (p ≤ 0.001, unless stated otherwise) increased 0–6 h weighted mean FEV 1 versus Umeclidinium in Umeclidinium-responders (+114 mL), versus vilanterol in vilanterol-responders (+92 mL) and versus Umeclidinium (+70 mL) and vilanterol (+62 mL) in non-responders. Improvements in trough FEV 1 occurred with Umeclidinium/vilanterol versus Umeclidinium in Umeclidinium-responders (+77 mL), versus vilanterol in vilanterol-responders (+86 mL), and versus Umeclidinium (+42 mL [p = 0.020]) and vilanterol (+58 mL) in non-responders. All treatments were well tolerated. Conclusions Once-daily Umeclidinium/vilanterol significantly improved lung function in patients with COPD, with quantitatively greater improvements in patients identified as responders to Umeclidinium and vilanterol monotherapy than non-responders.
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Inhaled Umeclidinium in COPD Patients: A Review and Meta-Analysis
Drugs, 2016Co-Authors: Roy A. Pleasants, Tiansheng Wang, Jinming Gao, Huilin Tang, James F. DonohueAbstract:A number of new agents for the management of chronic obstructive pulmonary disease (COPD) are at different stages of development, including several inhaled long-acting antimuscarinics (LAMA). Long-acting bronchodilators are considered to be central to the management of COPD due to the evidence supporting their efficacy and safety. Umeclidinium, a LAMA, has recently been approved for the maintenance treatment of moderate to very severe COPD in a number of countries. This comprehensive review and pooled meta-analysis provides detailed information about the efficacy and safety of this agent. The pharmacokinetics and pharmacodynamics of Umeclidinium observed in phase I and II studies support its once-daily administration. Umeclidinium is rapidly cleared from blood, and renal or hepatic impairment do not lead to significant changes in drug disposition. A pooled analysis of phase III and comparative studies of Umeclidinium in patients with moderate to very severe COPD showed significant improvement in lung function measures, including trough forced expiratory volume in 1 s (FEV1), as well as in acute exacerbations of COPD, dyspnea, and quality of life. Adverse effects, including known anticholinergic effects, were uncommon with Umeclidinium. Limited data suggest the efficacy of Umeclidinium is similar to that of tiotropium. Umeclidinium is administered as a dry powder inhaler, provides adequate lung delivery in patients with moderate to very severe airflow obstruction, and appears to be easily used by patients. Umeclidinium provides a safe and effective option as an inhaled LAMA for the management of COPD.
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Magnitude of Umeclidinium/vilanterol lung function effect depends on monotherapy responses: Results from two randomised controlled trials
Respiratory medicine, 2016Co-Authors: James F. Donohue, Sally Kilbride, Dave Singh, Clara Munzu, Alison ChurchAbstract:Abstract Purpose Dual therapy with bronchodilators of different pharmacological classes may produce greater lung function improvements than either drug alone. However, the relationship between a patient's response to monotherapy and response to dual bronchodilator therapy is currently unknown. We aimed to investigate whether dual therapy with Umeclidinium/vilanterol provides additional benefit over Umeclidinium or vilanterol monotherapy in patients with chronic obstructive pulmonary disease (COPD) identified as responsive (increase from baseline in forced expiratory volume in 1s [FEV 1 ] of ≥12% and ≥200 mL, Day 1) or non-responsive to monotherapy. Methods In two randomised, double-blind, three-way complete-block, cross-over studies (DB2116132 n = 207; DB2116133 n = 182; intent-to-treat), all patients (moderate-to-very severe COPD) were randomised to 1 of 6 sequences and received once-daily Umeclidinium 62.5mcg, vilanterol 25mcg, and Umeclidinium/vilanterol 62.5/25mcg (one treatment/14-day period; 10–14-day washout). Key endpoints were 0–6 h weighted mean FEV 1 (Day 14) and trough FEV 1 (Day 15). Adverse events, vital signs and COPD exacerbations were assessed. Pooled data are presented. Results Umeclidinium/vilanterol significantly (p ≤ 0.001, unless stated otherwise) increased 0–6 h weighted mean FEV 1 versus Umeclidinium in Umeclidinium-responders (+114 mL), versus vilanterol in vilanterol-responders (+92 mL) and versus Umeclidinium (+70 mL) and vilanterol (+62 mL) in non-responders. Improvements in trough FEV 1 occurred with Umeclidinium/vilanterol versus Umeclidinium in Umeclidinium-responders (+77 mL), versus vilanterol in vilanterol-responders (+86 mL), and versus Umeclidinium (+42 mL [p = 0.020]) and vilanterol (+58 mL) in non-responders. All treatments were well tolerated. Conclusions Once-daily Umeclidinium/vilanterol significantly improved lung function in patients with COPD, with quantitatively greater improvements in patients identified as responders to Umeclidinium and vilanterol monotherapy than non-responders.
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Available online at www.sciencedirect.com
2016Co-Authors: James F. Donohue, Available From JamesAbstract:Umeclidinium
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Safety and tolerability of once-daily Umeclidinium/vilanterol 125/25 mcg and Umeclidinium 125 mcg in patients with chronic obstructive pulmonary disease: results from a 52-week, randomized, double-blind, placebo-controlled study
Respiratory research, 2014Co-Authors: James F. Donohue, Jean Brooks, Dianne O'dell, Dennis E. Niewoehner, Alison ChurchAbstract:Background The long-acting muscarinic antagonist (LAMA) Umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU. They are not indicated for the treatment of asthma.