Kerwin Edward M, Siler Thomas M, Arora Samir, Darken Patrick, Rose Earl, Reisner Colin
Clinical Research Institute of Southern Oregon, Medford, OR, USA.
Midwest Chest Consultants, St Charles, MO, USA.
Int J Chron Obstruct Pulmon Dis. 2018 May 8;13:1483-1494. doi: 10.2147/COPD.S164281. eCollection 2018.
This study investigated the efficacy, safety, and pharmacokinetics of the inhaled corticosteroid/long-acting β-agonist fixed-dose combination budesonide/formoterol fumarate (BFF) metered dose inhaler (MDI), compared with the monocomponents budesonide (BD) MDI and formoterol fumarate (FF) MDI, in patients with moderate-to-severe COPD.
In this Phase IIb, randomized, double-blind, four-period, five-treatment, incomplete-block, crossover study (NCT02196077), all patients received BFF MDI 320/9.6 μg and FF MDI 9.6 μg, and two of either BFF MDI 160/9.6 μg, BFF MDI 80/9.6 μg, or BD MDI 320 μg twice daily for 28 days. The primary efficacy endpoint was forced expiratory volume in 1 second area under the curve from 0 to 12 hours on Day 29. Secondary efficacy endpoints included additional lung function assessments, and evaluation of dyspnea and rescue medication use. Safety was monitored throughout. The systemic exposure to budesonide and formoterol was assessed on Day 29.
Overall, 180 patients were randomized. For forced expiratory volume in 1 second area under the curve from 0 to 12 hours on Day 29, all BFF MDI doses showed significant improvements versus BD MDI 320 μg (least squares mean differences 186-221 mL; all <0.0001), and BFF MDI 320/9.6 μg demonstrated a significant improvement versus FF MDI 9.6 μg (least squares mean difference 56 mL; =0.0013). Furthermore, all BFF MDI doses showed significant improvements versus BD MDI 320 μg for all lung function, dyspnea, and rescue medication use secondary efficacy endpoints. All BFF MDI doses were well tolerated, and the safety profile was not substantially different from the monocomponents. There was no evidence of clinically meaningful pharmacokinetic interactions when budesonide and formoterol were formulated together in BFF MDI.
The findings presented here confirm that BFF MDI 320/9.6 μg is an appropriate dose to take forward into Phase III studies in patients with COPD.
本研究调查了吸入性糖皮质激素/长效β受体激动剂布地奈德/富马酸福莫特罗（BFF）定量吸入器（MDI）与单一组分布地奈德（BD）MDI和富马酸福莫特罗（FF）MDI相比，在中重度慢性阻塞性肺疾病（COPD）患者中的疗效、安全性和药代动力学。
在这项IIb期、随机、双盲、四周期、五治疗组、不完全区组、交叉研究（NCT02196077）中，所有患者接受BFF MDI 320/9.6μg和FF MDI 9.6μg，以及BFF MDI 160/9.6μg、BFF MDI 80/9.6μg或BD MDI 320μg中的两种，每日两次，共28天。主要疗效终点是第29天0至12小时的1秒用力呼气容积曲线下面积。次要疗效终点包括额外的肺功能评估，以及呼吸困难和急救药物使用情况的评估。全程监测安全性。在第29天评估布地奈德和福莫特罗的全身暴露情况。
总体而言，180例患者被随机分组。对于第29天0至12小时的1秒用力呼气容积曲线下面积，所有BFF MDI剂量与BD MDI 320μg相比均有显著改善（最小二乘均值差异为186 - 221 mL；均<0.0001），且BFF MDI 320/9.6μg与FF MDI 9.6μg相比有显著改善（最小二乘均值差异为56 mL；P = 0.0013）。此外，所有BFF MDI剂量在所有肺功能、呼吸困难和急救药物使用等次要疗效终点方面与BD MDI 320μg相比均有显著改善。所有BFF MDI剂量耐受性良好，安全性概况与单一组分无实质性差异。当布地奈德和福莫特罗在BFF MDI中联合制剂时，没有临床意义上的药代动力学相互作用的证据。
此处呈现的研究结果证实，BFF MDI 320/9.6μg是推进COPD患者III期研究的合适剂量。
