Biohaven Pharmaceuticals, New Haven, CT, USA.
NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital/SLaM Biomedical Research Centre, King's College London, UK; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Lancet. 2019 Aug 31;394(10200):737-745. doi: 10.1016/S0140-6736(19)31606-X. Epub 2019 Jul 13.
Rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist, has shown efficacy in the acute treatment of migraine using a standard tablet formulation. The objective of this trial was to compare the efficacy, safety, and tolerability of a novel orally disintegrating tablet formulation of rimegepant at 75 mg with placebo in the acute treatment of migraine.
In this double-blind, randomised, placebo-controlled, multicentre phase 3 trial, adults aged 18 years or older with history of migraine of at least 1 year were recruited to 69 study centres in the USA. Participants were randomly assigned to receive rimegepant (75 mg orally disintegrating tablet) or placebo and instructed to treat a single migraine attack of moderate or severe pain intensity. The randomisation was stratified by the use of prophylactic medication (yes or no), and was carried out using an interactive web response system that was accessed by each clinical site. All participants, investigators, and the sponsor were masked to treatment group assignment. The coprimary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 h postdose. The efficacy analyses used the modified intention-to-treat population, which included all patients who were randomly assigned, had a migraine attack with pain of moderate or severe intensity, took a dose of rimegepant or placebo, and had at least one efficacy assessment after administration of the dose. The safety analyses included all randomly assigned participants who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT03461757, and is closed to accrual.
Between Feb 27 and Aug 28, 2018, 1811 participants were recruited and assessed for eligibility. 1466 participants were randomly assigned to the rimegepant (n=732) or placebo (n=734) groups, of whom 1375 received treatment with rimegepant (n=682) or placebo (n=693), and 1351 were evaluated for efficacy (rimegepant n=669, placebo n=682). At 2 h postdose, rimegepant orally disintegrating tablet was superior to placebo for freedom from pain (21% vs 11%, p<0·0001; risk difference 10, 95% CI 6-14) and freedom from the most bothersome symptom (35% vs 27%, p=0·0009; risk difference 8, 95% CI 3-13). The most common adverse events were nausea (rimegepant n=11 [2%]; placebo n=3 [<1%]) and urinary tract infection (rimegepant n=10 [1%]; placebo n=4 [1%]). One participant in each treatment group had a transaminase concentration of more than 3 × the upper limit of normal; neither was related to study medication, and no elevations in bilirubin greater than 2 × the upper limit of normal were reported. Treated participants reported no serious adverse events.
In the acute treatment of migraine, a single 75 mg dose of rimegepant in an orally disintegrating tablet formulation was more effective than placebo. Tolerability was similar to placebo, with no safety concerns.
Biohaven Pharmaceuticals.
利马喷他，一种小分子降钙素基因相关肽受体拮抗剂，在使用标准片剂制剂治疗偏头痛的急性发作方面显示出疗效。本试验的目的是比较 75 毫克新型口服崩解片制剂利马喷他与安慰剂在偏头痛急性治疗中的疗效、安全性和耐受性。
在这项双盲、随机、安慰剂对照、多中心的 3 期试验中，在美国的 69 个研究中心招募了年龄在 18 岁或以上、有至少 1 年偏头痛病史的成年人。参与者被随机分配接受利马喷他（75 毫克口服崩解片）或安慰剂，并被指示治疗单次中重度疼痛强度的偏头痛发作。随机分组按预防性药物的使用（是或否）分层，使用每个临床站点都可以访问的交互式网络响应系统进行。所有参与者、研究人员和赞助商都对治疗组分配进行了盲法。主要疗效终点是治疗 2 小时后无疼痛和无最困扰症状。疗效分析采用改良意向治疗人群，包括所有随机分配、偏头痛发作伴有中重度疼痛强度、服用利马喷他或安慰剂且在给药后至少有一次疗效评估的患者。安全性分析包括所有接受至少一剂研究药物的随机分配参与者。这项研究在 ClinicalTrials.gov 注册，编号为 NCT03461757，现已停止入组。
在 2018 年 2 月 27 日至 8 月 28 日期间，共招募了 1811 名参与者进行资格评估。1466 名参与者被随机分配至利马喷他（n=732）或安慰剂（n=734）组，其中 1375 名参与者接受了利马喷他（n=682）或安慰剂（n=693）治疗，1351 名参与者接受了疗效评估（利马喷他 n=669，安慰剂 n=682）。在治疗 2 小时后，利马喷他口服崩解片在无疼痛方面优于安慰剂（21% vs 11%，p<0.0001；风险差异 10，95%CI 6-14），在无最困扰症状方面也优于安慰剂（35% vs 27%，p=0.0009；风险差异 8，95%CI 3-13）。最常见的不良反应是恶心（利马喷他 n=11[2%]；安慰剂 n=3[<1%]）和尿路感染（利马喷他 n=10[1%]；安慰剂 n=4[1%]）。每个治疗组各有 1 名参与者的转氨酶浓度超过正常上限的 3 倍；均与研究药物无关，且未报告胆红素升高超过正常上限的 2 倍。接受治疗的参与者均未发生严重不良事件。
在偏头痛的急性治疗中，单次 75 毫克剂量的利马喷他口服崩解片制剂比安慰剂更有效。耐受性与安慰剂相似，无安全性问题。
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