Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has been approved for the preventive treatment of migraine, but its efficacy and safety in people who have been failed by conventional oral preventive migraine treatments has not yet been evaluated in a dedicated clinical trial. The ELEVATE trial evaluated the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in participants for whom two to four classes of conventional oral preventive treatments have failed. ELEVATE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3b trial done at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the UK, and the USA. Adults (18–80 years) with episodic migraine who had previously been failed by two to four classes of conventional oral treatments for migraine prevention were randomly assigned (1:1) using interactive web response technology to oral atogepant 60 mg once a day or placebo, stratified by baseline monthly migraine days, number of treatment classes participants have been failed by, and region. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the off-treatment hypothetical estimand (OTHE) population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods (whether on treatment or off treatment). The primary endpoint was analysed using a mixed model for repeated measures and a fixed-sequence procedure was used to control for multiple comparisons. The trial is registered with () and EudraCT (2019-003448-58), and is completed. Between March 5, 2021, and Aug 4, 2022, 540 participants were screened, 315 were randomly assigned, and 313 participants (280 [89%] female, 33 [11%] male, and 300 [96%] White) received at least one dose of study intervention. In the OTHE population, which comprised 309 participants (155 assigned to placebo and 154 to atogepant), least squares mean changes from baseline in monthly migraine days across 12 weeks were −1·9 (SE 0·4) with placebo and −4·2 (0·4) with atogepant (least squares mean difference −2·4, 95% CI −3·2 to −1·5; adjusted p<0·0001). The most common treatment-emergent adverse event with atogepant was constipation in 16 (10%) of 156 participants ( four [3%] of 157 for placebo). Serious adverse events occurred in four [3%] of 156 participants in the atogepant group none in the placebo group, and treatment-emergent adverse events resulting in treatment discontinuation occurred in three [2%] in the atogepant group two [1%] in the placebo group. Atogepant 60 mg once a day was safe, well tolerated, and showed significant and clinically relevant reductions in mean monthly migraine days compared with placebo across 12 weeks in patients with episodic migraine who had previously been failed by two to four classes of conventional oral preventive treatments. Atogepant might be an effective preventive treatment option for patients in this difficult-to-treat population. Allergan (now AbbVie).

中文翻译：

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atogepant 用于预防性治疗常规口服预防性治疗失败的成人阵发性偏头痛的安全性和有效性 (ELEVATE)：一项随机、安慰剂对照、3b 期试验

Atogepant是一种口服降钙素基因相关肽受体拮抗剂，已被批准用于偏头痛的预防性治疗，但其对传统口服预防性偏头痛治疗失败的人群的疗效和安全性尚未在专门的临床试验中得到评估。 ELEVATE 试验评估了 atogepant 用于预防性治疗阵发性偏头痛的安全性、耐受性和有效性，受试者为两到四类常规口服预防性治疗失败的受试者。 ELEVATE 是一项随机、双盲、安慰剂对照、平行组 3b 期试验，在加拿大、捷克共和国、丹麦、法国、德国、匈牙利、意大利、荷兰、波兰、俄罗斯、西班牙、英国和美国。使用交互式网络响应技术将患有阵发性偏头痛的成年人（18-80 岁）先前通过两到四类预防偏头痛的常规口服治疗失败的患者被随机分配（1:1），接受口服 atogepant 60 mg 每天一次或安慰剂，按基线每月偏头痛天数、参与者失败的治疗课程数量和地区进行分层。主要终点是治疗结束假设估计 (OTHE) 人群中 12 周治疗期内平均每月偏头痛天数相对于基线的变化，其中包括安全人群中的参与者（所有接受≥1 剂研究干预的参与者）谁拥有基线期和基线后 4 周期间（无论是否接受治疗）的可评估数据。使用混合模型进行重复测量来分析主要终点，并使用固定序列程序来控制多重比较。该试验已在()和EudraCT (2019-003448-58)上注册，并已完成。 2021 年 3 月 5 日至 2022 年 8 月 4 日期间，对 540 名参与者进行了筛选，其中 315 名被随机分配，313 名参与者（280 名 [89%] 女性、33 名 [11%] 男性和 300 名 [96%] 白人）在至少一剂研究干预。在由 309 名参与者组成的 OTHE 人群中（155 名被分配安慰剂，154 名被分配 atogepant），12 周内每月偏头痛天数相对于基线的最小二乘平均变化为：安慰剂组为 -1·9 (SE 0·4)，安慰剂组为 -4· 2 (0·4) 与 atogepant（最小二乘平均差 -2·4，95% CI -3·2 至 -1·5；调整 p<0·0001）。 atogepant 最常见的治疗中出现的不良事件是便秘，156 名参与者中有 16 名（10%）（安慰剂组有 157 名参与者中有 4 名（3%））。 atogepant 组 156 名参与者中，有 4 名 [3%] 发生严重不良事件，而安慰剂组则没有；而 atogepant 组 3 名 [2%] 发生了导致治疗中断的治疗突发不良事件，第 2 组 [1%] 发生了严重不良事件。安慰剂组。 Atogepant 60 mg 每天一次是安全的，耐受性良好，研究结果显示，与安慰剂相比，在 12 周内，对于先前接受过两到四类常规口服预防治疗无效的阵发性偏头痛患者，每月平均偏头痛天数显着减少，并具有临床相关性。对于这一难以治疗的人群，Atogepant 可能是一种有效的预防性治疗选择。艾尔建（现为艾伯维）。