Early Onset of Efficacy and Consistency of Response Across Multiple Migraine Attacks From the Randomized COMPASS Study: AVP-825 Breath Powered® Exhalation Delivery System (Sumatriptan Nasal Powder) vs Oral Sumatriptan
Early Onset of Efficacy and Consistency of Response Across Multiple Migraine Attacks From the Randomized COMPASS Study: AVP-825 Breath Powered® Exhalation Delivery System (Sumatriptan Nasal Powder) vs Oral Sumatriptan
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DOI：
10.1111/head.13105
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发表时间：
2017-06-01
期刊：
影响因子：
5
通讯作者：
Siffert, Joao
中科院分区：
文献类型：
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作者：
Silberstein, Stephen;Winner, Paul K.;Siffert, Joao
目的：基于额外的预定结果和COMPASS的事后分析，进一步表征AVP-825的临床效用。COMPASS是一项AVP-825与100 mg口服舒马曲坦（NCT01667679）的3期疗效比较试验。AVP-825于2016年1月被美国食品和药物管理局批准，名称为ONZETRA((R)) Xsail((R))（舒马曲坦鼻粉），用于急性治疗有或无先兆的成人偏头痛。davp -825是一种利用患者自身呼吸将低剂量舒马曲坦粉末输送到狭窄鼻阀以外的鼻腔后上部区域的给药系统，该区域与血管粘膜排列，有利于药物快速吸收进入体循环。AVP-825的推荐剂量为22mg舒马曲坦粉末，每只鼻孔一个11mg鼻塞，经鼻给药约15- 16mg舒马曲坦。COMPASS试验比较了AVP-825 22-100 mg口服舒马曲坦治疗多次偏头痛的疗效、安全性和耐受性终点。设计/方法compass是一项随机、多中心、双虚拟、交叉、多发作、比较疗效的研究，有两个12周的双盲期。每个月2-8次偏头痛发作的患者按1:1的比例随机分配到AVP-825（22毫克）加口服安慰剂或相同的安慰剂递送系统加100毫克口服舒马曲坦，然后患者在第二期切换治疗。患者在发病后1小时内每周期最多治疗5次符合条件的偏头痛，即使发作强度较轻。主要终点（spider -30，定义为从给药到30分钟疼痛强度差异的总和）、关键次要疗效终点和安全性评估的结果已在主要出版物中报告（Tepper等人，2015）。本文报告了其他预先指定的结果，包括基线严重程度为轻度与中度/重度时治疗的发作的spider -30，经历多次偏头痛发作的患者持续反应和效果一致性的测量，以及评估偏头痛完全缓解（定义为无疼痛和偏头痛相关症状，包括恶心、呕吐、畏光和电话恐惧症）、疼痛缓解时间的事后分析结果。到有意义的疼痛缓解的时间，以及局部（发生在鼻子的给药部位）与全身治疗出现的不良事件（teae）。结果共有185例患者完成了两个治疗期，治疗和评估了1531例偏头痛发作（765例AVP-825, 766例口服舒马曲坦）。与口服舒马普坦相比，AVP-825治疗在给药后的前30分钟内提供了更大的偏头痛疼痛强度降低，无论疼痛是轻度（最小二乘平均spid30 =3.90 vs 0.24， P= 0.0013）还是中度/重度（最小二乘平均spid30 =13.83 vs 10.07， P= 0.0002）。在给药后15至90分钟的每个时间点，AVP-825治疗与100 mg口服舒马曲坦治疗相比，偏头痛发作完全自由的比例更大，具有统计学意义。AVP-825治疗导致获得疼痛缓解的几率更大(优势比，OR=1.29， P
ObjectiveTo further characterize the clinical utility of AVP-825 based on additional prespecified outcomes and post hoc analyses of COMPASS, a Phase 3 comparative efficacy trial of AVP-825 vs 100 mg oral sumatriptan (NCT01667679). AVP-825 was approved in January 2016 by the US Food and Drug Administration under the name ONZETRA((R)) Xsail((R)) (sumatriptan nasal powder) for the acute treatment of migraine with or without aura in adults.BackgroundAVP-825 is a delivery system that uses a patient's own breath to deliver low-dose sumatriptan powder to the upper posterior regions of the nasal cavity beyond the narrow nasal valve, areas lined with vascular mucosa conducive to rapid drug absorption into the systemic circulation. The recommended dose of AVP-825 is 22 mg sumatriptan powder administered as one 11 mg nosepiece in each nostril, which delivers approximately 15-16 mg of sumatriptan intranasally. The COMPASS trial compared AVP-825 22-100 mg oral sumatriptan across multiple migraine attacks for efficacy, safety, and tolerability endpoints.Design/MethodsCOMPASS was a randomized, multicenter, double-dummy, crossover, multiattack, comparative efficacy study with two 12-week double-blind periods. Patients with 2-8 migraine attacks/month were randomized 1:1 to AVP-825 (22 mg) plus oral placebo or an identical placebo delivery system plus 100 mg oral sumatriptan for the first period, and then patients switched treatments for the second period. Patients treated up to 5 qualifying migraines per period within 1 h of onset, even if the intensity of the attack was mild. Results from the primary endpoint (SPID-30, defined as the sum of pain intensity differences from dosing to 30 minutes), key secondary efficacy endpoints and safety assessments have been reported in the primary publication (Tepper et al., 2015). This article reports additional prespecified outcomes, including the SPID-30 for attacks treated when baseline severity was mild vs moderate/severe, measures of sustained response and consistency of effect in patients who experienced multiple migraine attacks, and the results of post hoc analyses performed to assess total migraine freedom (defined as no pain and no migraine-associated symptoms, including nausea, vomiting, photophobia, and phonophobia), time to pain freedom, time to meaningful pain relief, and local (occurring at the site of administration in the nose) vs systemic treatment-emergent adverse events (TEAEs).ResultsA total of 185 patients completed both treatment periods, yielding 1,531 migraine attacks which were treated and assessed (765 AVP-825, 766 oral sumatriptan). Treatment with AVP-825 provided greater reduction in migraine pain intensity which was statistically significant vs oral sumatriptan in the first 30 minutes postdose regardless of whether attacks were treated when pain was mild (least squares mean SPID-30=3.90 vs 0.24, P=.0013) or moderate/severe (least squares mean SPID-30=13.83 vs 10.07, P=.0002). At every time point from 15 to 90 minutes postdose, the proportion of attacks achieving total migraine freedom was greater and statistically significant after treatment with AVP-825 vs 100 mg oral sumatriptan. AVP-825 treatment resulted in greater odds of achieving pain freedom (odds ratio, OR=1.29, P