比较慢性阻塞性肺疾病患者使用干粉吸入器和压力定量吸入器制剂的超细布地奈德/福莫特罗/格隆溴铵：TRI-D 随机对照试验。

Comparison of Dry-Powder Inhaler and Pressurized Metered-Dose Inhaler Formulations of Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium in Patients with COPD: The TRI-D Randomized Controlled Trial.

机构信息

Insaf Respiratory Research Institute, Wiesbaden, Germany.

Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Łódź, Poland.

出版信息

Int J Chron Obstruct Pulmon Dis. 2021 Jan 14;16:79-89. doi: 10.2147/COPD.S291030. eCollection 2021.

BACKGROUND

Three 52-week studies in COPD have assessed the efficacy and safety of single-inhaler extrafine formulation triple therapy combining beclomethasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) delivered via pressurized metered-dose inhaler (pMDI). BDP/FF/G is now being developed for delivery via multi-dose dry-powder inhaler (DPI; NEXThaler). This study aimed to demonstrate non-inferiority of BDP/FF/G DPI vs pMDI for lung function.

METHODS

Multicenter, randomized, double-blind, double-dummy, active-controlled, three-way cross-over study in patients with COPD and post-bronchodilator forced expiratory volume in 1 second (FEV) 30-80% predicted. Patients received BDP/FF/G 100/6/10µg via DPI and pMDI, and BDP/FF 100/6µg via pMDI, all two inhalations twice daily for four weeks, with treatments separated by two-week washout. The two co-primary objectives were to demonstrate non-inferiority between the two BDP/FF/G formulations for FEV area under the curve between 0 and 12 hours post-dose (AUC) normalized by time and trough FEV at 24 hours, both on Day 28. EudraCT 2017-004405-41.

RESULTS

Of 449 patients screened, 366 were randomized, with 342 (93.4%) completing all three treatment periods. The primary objectives were met, with changes from baseline in FEV AUC and trough FEV on Day 28 similar for the two BDP/FF/G formulations, and the confidence intervals for the difference lying entirely within the pre-specified non-inferiority criterion (-50mL): -20 (-35, -6) mL and 3 (-15, 20) mL for AUC and trough FEV, respectively. BDP/FF/G pMDI and DPI were statistically superior to BDP/FF for these endpoints (p<0.001). A similar proportion of patients experienced adverse events with each treatment (15.5%, 18.7% and 15.4% with BDP/FF/G DPI and pMDI, and BDP/FF, respectively); the majority were mild or moderate, with few related to treatment.

CONCLUSION

Extrafine BDP/FF/G DPI and pMDI demonstrated similar efficacy and safety in patients with COPD, supporting the DPI formulation as a valid alternative.

背景

三项为期 52 周的 COPD 研究评估了丙酸倍氯米松（BDP）、富马酸福莫特罗（FF）和格隆溴铵（G）三联干粉吸入剂（DPI）联合用药治疗 COPD 的疗效和安全性，药物通过压力定量气雾剂（pMDI）吸入给药。BDP/FF/G 目前正在开发通过多剂量干粉吸入器（DPI；NEXThaler）给药。本研究旨在证明 BDP/FF/G DPI 与 pMDI 相比在肺功能方面非劣效。

方法

这是一项多中心、随机、双盲、双模拟、活性对照、三交叉研究，纳入了支气管扩张剂后用力呼气量（FEV）占预计值 30-80%的 COPD 患者。患者接受 BDP/FF/G 100/6/10μg 或 BDP/FF 100/6μg 治疗，通过 DPI 或 pMDI 吸入，每日两次，每次两吸，持续四周，每两周洗脱一次。两个主要次要终点是证明两种 BDP/FF/G 制剂在给药后 0 至 12 小时（AUC）与时间的比值（FEV）和 24 小时时的谷值 FEV 在第 28 天具有非劣效性。EudraCT 2017-004405-41。

结果

在筛选的 449 名患者中，366 名患者被随机分配，其中 342 名（93.4%）完成了所有三个治疗期。主要终点达到，BDP/FF/G 两种制剂在第 28 天的 FEV AUC 和谷值 FEV 较基线的变化相似，置信区间完全符合预先设定的非劣效性标准（-50mL）：-20（-35，-6）mL 和 3（-15，20）mL，分别用于 AUC 和谷值 FEV。BDP/FF/G pMDI 和 DPI 在这些终点上均优于 BDP/FF（p<0.001）。两种治疗方案的不良事件发生率相似（BDP/FF/G DPI 和 pMDI 组为 15.5%、18.7%和 15.4%，BDP/FF 组为 15.4%）；大多数为轻度或中度，少数与治疗相关。