Department of Neurology, Mayo Clinic, Phoenix, AZ, USA; Atria Academy of Science and Medicine, New York, NY, USA.
Department of Neurology, King's College London, London, UK; Department of Neurology, University of California, Los Angeles, CA, USA.
Lancet. 2023 Dec 16;402(10419):2307-2316. doi: 10.1016/S0140-6736(23)01683-5. Epub 2023 Nov 15.
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 ClinicalTrials.gov (NCT04492020).
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.
Ubrogepant 是一种降钙素基因相关肽（CGRP）受体拮抗剂，已被批准用于偏头痛的急性治疗。前驱期是偏头痛发作的最早阶段，其特征是头痛发作前出现非先兆症状。本试验旨在评估ubrogepant 100mg 在前驱期给药时用于偏头痛急性治疗的疗效、安全性和耐受性，与安慰剂相比。
这项 PRODROME 试验是一项在美国 75 个研究中心和头痛诊所进行的为期 3 个月、多中心、随机、双盲、安慰剂对照、交叉试验，共纳入了 75 个研究中心和头痛诊所。符合条件的参与者为年龄在 18-75 岁之间的成年人，至少有 1 年的偏头痛病史，伴或不伴先兆，每月有 2-8 次偏头痛发作，在筛选前 3 个月内每次偏头痛发作均为中度至重度头痛。符合条件的参与者被随机分配（1:1）接受安慰剂治疗首次合格的前驱期事件，接受 ubrogepant 100mg 治疗第二次合格的前驱期事件，或接受 ubrogepant 100mg 治疗首次合格的前驱期事件，接受安慰剂治疗第二次合格的前驱期事件。一个自动交互式网络响应系统使用 4 个随机排列的块来管理随机分组。在研究期间，所有给予干预措施和评估结果的人员都对分组情况进行了屏蔽。进行数据分析的人员在研究完成后不进行分组屏蔽。在双盲治疗期间，每个参与者在每次合格的前驱期事件发作时被指示口服两片研究药物。主要终点为在研究药物剂量后 24 小时内无中度或重度强度头痛；疗效分析采用改良意向治疗（mITT）人群进行，定义为所有在治疗期间接受研究药物治疗的参与者中，至少有一次头痛评估的随机分配参与者。安全性人群包括至少接受一次研究药物治疗的所有治疗参与者。该试验在 ClinicalTrials.gov（NCT04492020）上注册。
在 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。安全性人群包括 480 名参与者，mITT 人群包括 477 名参与者；480 名参与者中，421 名（88%）为女性，59 名（12%）为男性。在接受 ubrogepant 治疗的 418 次合格前驱期事件中有 190 次（46%），在接受安慰剂治疗的 423 次合格前驱期事件中有 121 次（29%）在接受研究药物治疗后 24 小时内无中度或重度头痛（比值比 2.09，95%置信区间 1.63-2.69；p<0.0001）。在接受 ubrogepant 治疗的 456 次合格前驱期事件中有 77 次（17%）和在接受安慰剂治疗的 462 次事件中有 55 次（12%）在研究药物给药后 48 小时内发生不良事件。
Ubrogepant 在偏头痛发作时在前驱期给药时有效且耐受良好。
艾伯维。
