拉斯米丹治疗偏头痛急性期的 3 期随机、安慰剂对照、双盲研究。

IF 12.7 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Central Science Pub Date : 2019-07-01 DOI:10.1093/brain/awz134

Peter J Goadsby, Linda A Wietecha, Ellen B Dennehy, Bernice Kuca, Michael G Case, Sheena K Aurora, Charly Gaul

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引用次数: 0

摘要

在一项三期双盲随机对照研究中，5-羟色胺5-HT1F受体激动剂Lasmiditan对偏头痛患者的急性治疗有效。目前的研究旨在将这些发现复制到偏头痛患者中，包括有心血管病史的患者。这项前瞻性、双盲、3 期多中心研究随机分配有先兆和无先兆偏头痛患者（1:1:1:1 比例）口服拉斯米丹 200 毫克、100 毫克、50 毫克或安慰剂。研究人员要求患者在偏头痛发作（至少中等程度且未见好转）后4小时内在家中服药。主要目的是评估每种剂量的拉斯米迪坦与安慰剂相比，服药后2小时患者头痛不痛和最令人烦恼的症状消失的比例（NCT02605174）。对患者（n = 3005）进行了分配和治疗（n = 2583，安全人群）：1938 例拉斯米坦（200 毫克 n = 528 例，100 毫克 n = 532 例，50 毫克 n = 556 例，纳入主要分析）和 645 例安慰剂（540 例，纳入主要分析）。大多数患者（79.2%）在基线时除偏头痛外，还有≥1个心血管风险因素。拉斯米坦与2小时后疼痛缓解率明显增加有关（拉斯米坦200毫克：38.8%，几率比2.2%）：31.4%，几率比 1.7，1.3-2.2，P <0.001；50 毫克：28.6%，几率比 1.5，1.1-1.9，P = 0.003，安慰剂：21.3%）和 2 小时内无最令人烦恼的症状（拉斯米丹 200 毫克：48.7%，几率比 1.5，1.1-1.9，P = 0.003，安慰剂：21.3%）：40.8%，几率比 1.4，1.1-1.8，P = 0.009，安慰剂为 33.5%）。在服用拉斯米坦 200、100 和 50 毫克的 649 位患者中，分别有 253 位（39.0%）、635 位患者中的 229 位（36.1%）和 654 位患者中的 166 位（25.4%）出现了治疗突发不良事件，而在服用安慰剂的 645 位患者中，则有 75 位（11.6%）出现了治疗突发不良事件。大多数不良反应与中枢神经系统有关，包括头晕、嗜睡和麻痹。在所有测试的口服剂量下，Lasmiditan在服药后2小时对偏头痛的急性治疗均有效。疗效和安全性与之前的第三阶段研究结果一致。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine.

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Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine.

Lasmiditan, a serotonin 5-HT1F receptor agonist, was effective for acute treatment of patients with migraine in a phase 3 double-blind randomized controlled study. The current study was designed to replicate these findings in a generalizable population of patients with migraine, including those with a cardiovascular medical history. This prospective, double-blind, phase 3 multicentre study randomly assigned patients with migraine with and without aura (1:1:1:1 ratio) to oral lasmiditan 200 mg, 100 mg, 50 mg, or placebo. Patients were instructed to dose at home within 4 h of onset of migraine attack of at least moderate intensity and not improving. The primary objective was to assess the proportion of patients' headache pain-free and most bothersome symptom-free at 2 h post-dose for each dose of lasmiditan versus placebo (NCT02605174). Patients (n = 3005) were assigned and treated (n = 2583, safety population): 1938 lasmiditan (200 mg n = 528, 100 mg n = 532, and 50 mg n = 556 included in primary analysis) and 645 placebo (540 included in primary analysis). Most patients (79.2%) had ≥1 cardiovascular risk factor at baseline, in addition to migraine. Lasmiditan was associated with significantly more pain freedom at 2 h (lasmiditan 200 mg: 38.8%, odds ratio 2.3, 95% confidence interval 1.8-3.1, P < 0.001; 100 mg: 31.4%, odds ratio 1.7, 1.3-2.2, P < 0.001; 50 mg: 28.6%, odds ratio 1.5, 1.1-1.9, P = 0.003 versus placebo 21.3%) and freedom from most bothersome symptom at 2 h (lasmiditan 200 mg: 48.7%, odds ratio 1.9, 95% confidence interval 1.4-2.4, P < 0.001; 100 mg: 44.2%, odds ratio 1.6, 1.2-2.0, P < 0.001; 50 mg: 40.8%, odds ratio 1.4, 1.1-1.8, P = 0.009 versus placebo 33.5%). Treatment-emergent adverse events were reported in 253 of 649 (39.0%), 229 of 635 (36.1%), and 166 of 654 (25.4%) of patients on lasmiditan 200, 100, and 50 mg, respectively, versus 75 of 645 (11.6%) on placebo. Most adverse events were CNS-related and included dizziness, somnolence and paraesthesia. Lasmiditan was effective at 2 h post-dose for acute treatment of migraine at all oral doses tested. Efficacy and safety were consistent with the previous phase 3 study.

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来源期刊

ACS Central Science Chemical Engineering-General Chemical Engineering

CiteScore

25.50

自引率

0.50%

发文量

194

审稿时长

10 weeks

期刊介绍： ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.