Reisner Colin, Pearle James, Kerwin Edward M, Rose Earl St, Darken Patrick
Pearl - a member of the AstraZeneca Group, Morristown, NJ, USA.
AstraZeneca, Gaithersburg, MD, USA.
Int J Chron Obstruct Pulmon Dis. 2018 Jun 19;13:1965-1977. doi: 10.2147/COPD.S166455. eCollection 2018.
To determine the efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI 36/9.6, 36/7.2, 18/9.6, 9/9.6 µg) using innovative co-suspension delivery technology, compared with glycopyrrolate (GP) MDI 36 µg and formoterol fumarate (FF) MDI 9.6 µg, in patients with moderate-to-severe COPD.
In this Phase IIb, randomized, double-blind, balanced incomplete-block, two-period, cross-over study (NCT01349816), patients received treatment twice-daily for 7 days. The primary efficacy endpoint was forced expiratory volume in 1 second (FEV) area under the curve from 0 to 12 hours (AUC) on Day 7. Secondary efficacy endpoints were peak change from baseline in FEV through 2 hours; time to onset of action (≥10% improvement in mean FEV); proportion of patients achieving ≥12% improvement in FEV on Day 1; peak change from baseline in inspiratory capacity (IC) on Days 1 and 7; change from baseline in morning pre-dose FEV; peak change from baseline in FEV through 6 hours; and change from baseline in mean evening 12-hour post-dose trough FEV on Day 7. Safety was assessed.
All 185 randomized patients received treatment. All doses of GFF MDI significantly improved the primary endpoint compared with GP MDI 36 µg (all ≤0.0137). For peak change in FEV and IC and time to onset of action secondary endpoints, ≥2 doses of GFF MDI demonstrated superiority to GP MDI 36 µg. No significant differences were observed between GFF MDI and FF MDI 9.6 µg for primary and secondary endpoints. The incidence of adverse events was similar between treatments.
While all doses of GFF MDI were superior to GP MDI 36 µg for the primary end-point, in this study neither superiority of GFF MDI to FF MDI 9.6 µg nor a clear dose-response was observed. All treatments were well tolerated with no unexpected safety findings.
在中重度慢性阻塞性肺疾病（COPD）患者中，对比格隆溴铵/富马酸福莫特罗定量吸入器（GFF MDI 36/9.6、36/7.2、18/9.6、9/9.6微克）采用创新共悬浮递送技术与格隆溴铵（GP）MDI 36微克和富马酸福莫特罗（FF）MDI 9.6微克的疗效和安全性。
在这项IIb期、随机、双盲、平衡不完全区组、两阶段、交叉研究（NCT01349816）中，患者每日接受两次治疗，为期7天。主要疗效终点为第7天0至12小时曲线下1秒用力呼气容积（FEV）面积（AUC）。次要疗效终点包括2小时内FEV相对于基线的峰值变化；起效时间（平均FEV改善≥10%）；第1天FEV改善≥12%的患者比例；第1天和第7天吸气容量（IC）相对于基线的峰值变化；晨起给药前FEV相对于基线的变化；6小时内FEV相对于基线的峰值变化；以及第7天晚上12小时给药后FEV谷值相对于基线的平均变化。评估安全性。
所有随机分组的185例患者均接受了治疗。与36微克的GP MDI相比，所有剂量的GFF MDI均显著改善了主要终点（均≤0.0137）。对于FEV和IC的峰值变化以及起效时间次要终点，≥2剂GFF MDI显示出优于36微克的GP MDI。在主要和次要终点方面，GFF MDI与9.6微克的FF MDI之间未观察到显著差异。各治疗组不良事件发生率相似。
虽然所有剂量的GFF MDI在主要终点方面均优于36微克的GP MDI，但在本研究中，未观察到GFF MDI优于9.6微克的FF MDI，也未观察到明确的剂量反应。所有治疗耐受性良好，未发现意外的安全性结果。
