Fast onset of action of glycopyrronium compared with tiotropium in patients with moderate to severe COPD — A randomised, multicentre, crossover trial

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• 作者：Henrik Watz^a ; ^{h.watz@pulmoresearch.de} ; Claudia Mailä ; nder^b ; ^{claudia.mailaender@novartis.com} ; Christoph May^b ; ^{christoph.may@novartis.com} ; Monika Baier^b ; ^{monika.baier@novartis.com} ; Anne-Marie Kirsten^a ; ^{a.kirsten@pulmoresearch.de}
• 关键词：Chronic obstructive pulmonary disease ; Glycopyrronium ; Tiotropium ; Airway resistance ; Fast onset ; Body plethysmography
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：42
• 期：Complete
• 页码：13-20
• 全文大小：853 K
• 卷排序：42

文摘

Long-acting bronchodilators, including anticholinergics glycopyrronium and tiotropium, are central to symptomatic management of chronic obstructive pulmonary disease (COPD). In patients with moderate to severe COPD, glycopyrronium has demonstrated comparable efficacy to open-label and single-blinded tiotropium, but with faster onset of bronchodilation. The FAST study assessed the efficacy of glycopyrronium compared with tiotropium in serial spirometry and body plethysmography assessments to further characterize the earlier onset of action associated with glycopyrronium.MethodsIn this German multicentre, randomised, double-blinded, double-dummy, cross-over study, patients with moderate-to-severe COPD received single-dose of glycopyrronium 44 μg and tiotropium 18 μg via the Breezhaler® and Handihaler® devices, respectively. Primary objective was to demonstrate superiority of glycopyrronium over tiotropium in terms of improvement in forced expiratory volume in 1 s as assessed by the area under the curve from 0 to 2 h (FEV1 AUC 0&ndash;2h). Secondary endpoints were functional residual capacity (FRC), residual volume (RV), inspiratory capacity (IC), and specific airway resistance (sRaw), all measured by body plethysmography.ResultsOf the 152 patients randomised, 99.3% completed the study. After inhalation of the single dose, glycopyrronium demonstrated superiority over tiotropium in early bronchodilation as assessed by improvement in FEV1 AUC0&ndash;2h (least squares mean treatment difference = 37 mL; 95% CI: 16, 59 mL; p < 0.01) and FEV1 at 15 min post-dose (least square mean treatment difference = 36 mL; 95% CI: 14, 58 mL; p < 0.01). Both treatments showed similar improvements in FRCpleth, RV, and IC. Glycopyrronium showed statistically significant improvement in sRaw compared with tiotropium over the first 90 min after dosing, with the difference of 0.184 kPa × s at 90 min post-dose (95% CI: 0.315,0.054 kPa × s; p < 0.01).ConclusionsGlycopyrronium was superior to tiotropium in terms of early bronchodilation. Although both glycopyrronium and tiotropium showed similar improvements in static lung volume parameters, glycopyrronium reduced specific airway resistance faster than tiotropium, which could in part explain the earlier FEV1 response seen with glycopyrronium.Trial registrationClinicalTrials.govNCT01922271.