Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine
Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine
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DOI：
10.1093/brain/awz134
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发表时间：
2019-07-01
期刊：
影响因子：
14.5
通讯作者：
Gaul, Charly
中科院分区：
文献类型：
--
作者：
Goadsby, Peter J.;Wietecha, Linda A.;Gaul, Charly
在一项III期双盲随机对照研究中，5-羟色胺5-HT 1F受体激动剂Lasmiditan对偏头痛患者的急性治疗有效。目前的研究旨在在偏头痛患者的可推广人群中复制这些发现，包括那些有心血管病史的患者。这项前瞻性、双盲、III期、多中心研究将有先兆和无先兆的偏头痛患者（1：1：1：1比例）随机分配至口服lasmiditan 200 mg、100 mg、50 mg或安慰剂组。指导患者在偏头痛发作4小时内在家服药，偏头痛发作至少为中等强度且未改善。主要目的是评估每种剂量的lasmiditan与安慰剂相比，在给药后2小时无头痛疼痛和无最令人烦恼的头痛的患者比例（NCT 02605174）。患者（n = 3005）被分配并接受治疗（n = 2583，安全性人群）：1938例lasmiditan（200 mg n = 528、100 mg n = 532和50 mg n = 556，纳入主要分析）和645例安慰剂（540例纳入主要分析）。除偏头痛外，大多数患者（79.2%）在基线时有51个心血管危险因素。Lasmiditan与2小时时疼痛缓解率显著更高相关（拉西米坦200 mg：38.8%，比值比2.3，95%置信区间1.8-3.1，P < 0.001; 100 mg：31.4%，比值比1.7，1.3-2.2，P < 0.001; 50 mg：28.6%，比值比1.5，1.1-1.9，P = 0.003与安慰剂21.3%相比），2 h时无最令人烦恼的症状（拉西米坦200 mg：48.7%，比值比1.9，95%置信区间1.4-2.4，P < 0.001; 100 mg：44.2%，比值比1.6，1.2-2.0，P < 0.001; 50 mg：40.8%，比值比1.4，1.1-1.8，P = 0.009，安慰剂组为33.5%）。在接受lasmiditan 200、100和50 mg治疗的患者中，分别有253/649例（39.0%）、229/635例（36.1%）和166/654例（25.4%）报告了治疗后出现的不良事件，而在接受安慰剂治疗的患者中，分别有75/645例（11.6%）报告了治疗后出现的不良事件。大多数不良事件与CNS相关，包括头晕、嗜睡和感觉异常。在所有测试的口服剂量下，拉司米坦在给药后2小时对偏头痛的急性治疗有效。疗效和安全性与既往III期研究一致。
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 51 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.