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A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD.

ABSTRACT: 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 (FEV1) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0-24?h and patient-reported outcomes (transition dyspnoea index score and St George's 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 FEV1 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 FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

SUBMITTER: Rheault T

PROVIDER: S-EPMC5005182 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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A randomised, open-label study of umeclidinium <i>versus</i> glycopyrronium in patients with COPD.

Rheault Tara T Khindri Sanjeev S Vahdati-Bolouri Mitra M Church Alison A Fahy William A WA

ERJ open research 20160427 2

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 <i>via</i> Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced ...[more]

PMID: 27730198

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Project description:BackgroundDual bronchodilation combining a long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials.MethodsThe CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 μg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments.ResultsThe study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV1 (Δ = +101 mL) and a TDI (Δ = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies.ConclusionsIND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments.Trial registrationClinicalTrials.gov number: NCT01985334 .

Project description:BACKGROUND: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. METHODS: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??g once-daily, umeclidinium 62.5??g once-daily or salmeterol 50??g 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. RESULTS: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. CONCLUSIONS: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.

Project description:BACKGROUND:Umeclidinium bromide (UMEC) is an inhaled long-acting muscarinic antagonist in development for chronic obstructive pulmonary disease (COPD). METHODS:This was a multicentre, randomised, double-blind, placebo-controlled, three-way cross-over, incomplete block study to evaluate UMEC 15.6, 31.25, 62.5, and 125 ?g administered once daily (QD), and UMEC 15.6 ?g and 31.25 ?g administered twice daily (BID), over 7 days in patients with COPD. Tiotropium was included as an open-label treatment arm. The primary efficacy endpoint was trough forced expiratory volume in 1 second (FEV1) on Day 8. Secondary efficacy endpoints included weighted mean FEV1 over 0-24 hours after morning dosing on Day 7, and serial FEV1 at each time point over 24 hours after morning dosing on Day 7. Safety and pharmacokinetics were also examined. RESULTS:One hundred and sixty-three patients (mean age 59.5 years, 52% female) were randomised. Based on the population dose-response model of trough FEV1 data, the geometric mean potency (ED50) of UMEC was 37 ?g (95% confidence interval [CI]: 18, 57) with a predicted maximum intrinsic efficacy (Emax) at trough of 0.185 L (95% CI: 0.153, 0.218) after QD dosing. UMEC 125 ?g QD demonstrated the greatest improvements in measure of lung function compared with doses of 62.5 ?g and below. UMEC 125 ?g QD exhibited more consistent increases in FEV1 from baseline across serial time points over 24 hours compared with other UMEC doses and tiotropium. Increases in FEV1 over 0-12 hours were similar to those observed over 12-24 hours after the second dose of UMEC was administered. UMEC was rapidly absorbed following inhaled dosing and eliminated from plasma. Adverse events, generally mild, were highest with UMEC 125 ?g QD (18%) compared with placebo (8%), tiotropium (4%) and other UMEC doses (5-12%). CONCLUSIONS:UMEC is a potent QD bronchodilator with geometric mean ED50 of 37 ?g. A dose ordering over the range of UMEC 15.6-125 ?g QD doses was observed, with UMEC 125 ?g showing the greatest improvement in trough FEV1.

Project description:BACKGROUND:Glycopyrronium tosylate is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged???9 years (Qbrexza™ [glycopyrronium] cloth, 2.4%). OBJECTIVE:This 44-week open-label extension study assessed glycopyrronium tosylate safety and descriptive efficacy in patients completing one of two, phase III, double-blind, vehicle-controlled, 4-week trials (NCT02530281; NCT02530294). METHODS:Patients aged???9 years with primary axillary hyperhidrosis were randomized 2:1 (glycopyrronium tosylate: vehicle, once daily) in the double-blind trials. Completers could receive open-label glycopyrronium tosylate for up to an additional 44 weeks. Treatment-emergent adverse events and local skin reactions were assessed. Descriptive efficacy assessments were gravimetrically measured sweat production, Hyperhidrosis Disease Severity Scale responder rate (??2 grade improvement), and Dermatology Life Quality Index/children's Dermatology Life Quality Index. RESULTS:Of 651 patients completing the double-blind trials, 564 (86.6%) entered the open-label extension; 550 were analyzed. Most patients experiencing treatment-emergent adverse events had mild or moderate events (>?90%). Discontinuation because of treatment-emergent adverse events remained low and relatively stable, with a cumulative rate of 8.0% (44/550) over 44 weeks. Common treatment-emergent adverse events (>?5%) were dry mouth (16.9%), vision blurred (6.7%), application-site pain (6.4%), nasopharyngitis (5.8%), and mydriasis (5.3%). Most patients (67.5%) had no local skin reactions; those occurring were predominantly mild/moderate. Glycopyrronium tosylate efficacy was maintained throughout the trial; at week 44, the Hyperhidrosis Disease Severity Scale responder rate was 63.2%, and improvements from baseline (double blind) in sweat production were -?71.3% and 8.7?±?6.2/6.2?±?4.9 for Dermatology Life Quality Index/children's Dermatology Life Quality Index. CONCLUSIONS:Daily long-term application of glycopyrronium tosylate for up to 48 weeks (double blind plus open label) was generally well tolerated and efficacy was maintained. No new safety signals emerged. TRIAL REGISTRY:Clinicaltrials.gov NCT02553798.

Project description:BackgroundAddition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.Materials and methodsIn this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices). The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.ResultsA total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001). IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01). TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05). The incidence of adverse events was similar for the two treatment groups.ConclusionIn patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.

Dataset Information

A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD.

Publications

A randomised, open-label study of umeclidinium <i>versus</i> glycopyrronium in patients with COPD.

Similar Datasets

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