糠酸莫米松福莫特罗固定剂量复方制剂在中重度至极重度 COPD 患者中的疗效和安全性：一项为期 52 周的 III 期试验结果。

BACKGROUND

A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F.

METHODS

This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex- smokers randomized to twice-daily treatment with inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV(1)) over 0-12 hours (AUC(0-12) FEV(1)) with MF/F versus MF, and in morning predose FEV(1) with MF/F versus F. Key secondary endpoints were quality of life (Saint George's Respiratory Questionnaire [SGRQ]), symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation.

RESULTS

Significant improvements in FEV(1) AUC(0-12) occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 (P ≤ 0.007). Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV(1) improvements with MF/F over the treatment period. Significant improvements in morning predose FEV(1) occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV(1) data were collected >2 days after the last dose of study treatment. Improvements in SGRQ total scores surpassed the minimum clinically important difference of at least 4 units with MF/F 400/10. MF/F 400/10 significantly reduced the time-to-first COPD exacerbation. Similar proportions of subjects in all five treatment groups reported treatment-emergent adverse events. Rates of pneumonia were low (≤1.0%) across treatment groups.

CONCLUSION

MF/F 400/10 μg twice daily was shown to be an effective therapy for patients with moderate to very severe COPD, and both MF/F 400/10 μg twice daily and MF/F 200/10 μg twice daily were well tolerated.

背景

一项针对中重度至极重度慢性阻塞性肺疾病（COPD）患者的糠酸莫米松/福莫特罗（MF/F）气雾剂临床试验，评估了 MF/F 固定剂量联合制剂的疗效和安全性。

方法

该多中心、双盲、安慰剂对照试验共 26 周的治疗期和 26 周的安全性延长期。受试者（n=1055；年龄≥40 岁）为当前吸烟者或曾吸烟者，随机接受每日两次 MF/F 400/10μg、MF/F 200/10μg、MF 400μg、F 10μg 或安慰剂治疗。该试验的主要复合终点是 MF/F 与 MF 相比，0-12 小时用力呼气量（FEV1）的平均变化（AUC（0-12）FEV1），以及 MF/F 与 F 相比，晨药前 FEV1 的变化。关键次要终点是生活质量（圣乔治呼吸问卷[SGRQ]）、无症状夜数和 26 周时部分稳定的 COPD，以及首次 COPD 加重的时间。

结果

MF/F 400/10 和 MF/F 200/10 组的 FEV1 AUC（0-12）在终点时显著改善，与 MF 400 组相比（P≤0.007）。MF/F 在 5 分钟内出现显著的支气管扩张，连续肺活量测定显示 MF/F 在治疗期间持续改善 FEV1。MF/F 两个剂量组均显著改善晨药前 FEV1，排除末次研究治疗剂量后>2 天采集晨 FEV1 数据的受试者后，进一步研究了这些效果。MF/F 400/10 组的 SGRQ 总分改善超过至少 4 个单位的最小临床重要差异。MF/F 400/10 显著降低首次 COPD 加重的时间。所有五组治疗组中，报告治疗出现不良事件的比例相似。各组肺炎发生率均较低（≤1.0%）。