Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist that is approved for acute treatment of migraine. The prodrome is the earliest phase of a migraine attack and is characterised by non-aura symptoms that precede headache onset. The aim of this trial was to evaluate the efficacy, safety, and tolerability of ubrogepant 100 mg compared with placebo for the acute treatment of migraine when administered during the prodrome. This PRODROME trial was a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial of ubrogepant 100 mg conducted at 75 research centres and headache clinics in the USA. Eligible participants were adults aged 18–75 years who had at least a 1-year history of migraine with or without aura and a history of two to eight migraine attacks per month with moderate to severe headache in each of the 3 months before screening. Eligible participants were randomly assigned (1:1) to either receive placebo to treat the first qualifying prodrome event and ubrogepant 100 mg to treat the second qualifying prodrome event or to receive ubrogepant 100 mg to treat the first qualifying prodrome event and placebo to treat the second qualifying prodrome event. An automated interactive web-response system used permuted blocks of four to manage randomisation. All people giving interventions and assessing outcomes were masked to group assignment during the study. People doing data analysis, which occurred after study completion, were not masked to group assignment. During the double-blind treatment period, each participant was instructed to orally take two tablets of the study drug at the onset of each qualifying prodrome event. The primary endpoint was absence of moderate or severe intensity headache within 24 h after study-drug dose; efficacy analyses were conducted with the modified intention-to-treat (mITT) population, defined as all randomly assigned participants with at least one headache assessment within 24 h after taking the study drug during the treatment period. The safety population included all treated participants who took at least one administration of study drug. The trial is registered with (). Between Aug 21, 2020, and April 19, 2022, 518 participants were randomly assigned to double-blind crossover treatment. The safety population included 480 participants and the mITT population included 477 participants; 421 (88%) of 480 participants were female and 59 (12%) were male. Absence of moderate or severe headache within 24 h after a dose occurred after 190 (46%) of 418 qualifying prodrome events that had been treated with ubrogepant and after 121 (29%) of 423 qualifying prodrome events that had been treated with placebo (odds ratio 2·09, 95% CI 1·63–2·69; p<0·0001). Adverse events that occurred within 48 h after study-drug administration were reported after 77 (17%) of 456 qualifying prodrome events that had been treated with ubrogepant and after 55 (12%) of 462 events that had been treated with placebo. Ubrogepant was effective and well tolerated for the treatment of migraine attacks when taken during the prodrome. AbbVie.

中文翻译：

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Ubrogepant 用于治疗前驱症状期间的偏头痛发作：在美国进行的一项 3 期、多中心、随机、双盲、安慰剂对照、交叉试验

Ubrogepant 是一种降钙素基因相关肽 (CGRP) 受体拮抗剂，被批准用于急性偏头痛治疗。前驱症状是偏头痛发作的最早阶段，其特征是头痛发作前的非先兆症状。该试验的目的是评估在前驱症状期间服用 ubrogepant 100 mg 与安慰剂相比，用于急性偏头痛治疗的有效性、安全性和耐受性。这项 PRODROME 试验是 ubrogepant 100 mg 的 3 期、多中心、随机、双盲、安慰剂对照、交叉试验，在美国 75 个研究中心和头痛诊所进行。符合资格的参与者是年龄在 18-75 岁之间的成年人，他们至少有 1 年有或无先兆偏头痛病史，并且在筛选前的 3 个月内每月有 2 至 8 次偏头痛发作，且每月有中度至重度头痛。符合条件的参与者被随机分配（1:1），接受安慰剂治疗第一次合格前驱症状事件，接受 ubrogepant 100 mg 治疗第二次合格前驱症状事件，或接受 ubrogepant 100 mg 治疗第一次合格前驱症状事件，接受安慰剂治疗第二次合格前驱症状事件。第二次资格赛前驱症状事件。自动交互式网络响应系统使用四个排列的块来管理随机化。在研究期间，所有提供干预和评估结果的人都被隐藏在小组分配中。研究完成后进行数据分析的人员不会被分组分配所掩盖。在双盲治疗期间，每位参与者被指示在每次符合资格的前驱症状事件发生时口服两片研究药物。主要终点是服用研究药物后 24 小时内没有出现中度或重度头痛；疗效分析采用改良意向治疗 (mITT) 人群进行，定义为在治疗期间服用研究药物后 24 小时内至少进行过一次头痛评估的所有随机分配的参与者。安全人群包括所有接受至少一次研究药物治疗的参与者。试验已注册为（）。2020年8月21日至2022年4月19日期间，518名参与者被随机分配接受双盲交叉治疗。安全人群包括 480 名参与者，mITT 人群包括 477 名参与者；480 名参与者中有 421 名（88%）为女性，59 名（12%）为男性。用药后 24 小时内无中度或重度头痛发生在用 ubrogepant 治疗的 418 例合格前驱症状事件中的 190 例（46%）和用安慰剂治疗的 423 例合格前驱症状事件中的 121 例（29%）后（赔率比率 2·09，95% CI 1·63–2·69；p<0·0001）。在接受 ubrogepant 治疗的 456 例合格前驱症状事件中，有 77 例（17%）报告了研究药物给药后 48 小时内发生的不良事件，在用安慰剂治疗的 462 例事件中，有 55 例（12%）报告了研究药物给药后 48 小时内发生的不良事件。在前驱症状期间服用 Ubrogepant 对于治疗偏头痛发作有效且耐受性良好。艾伯维.