Background

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.

Methods

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 , number , and is closed to accrual.

Findings

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.

Interpretation

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.

Funding

Biohaven Pharmaceuticals.

中文翻译：

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瑞格非特口腔崩解片治疗偏头痛的疗效，安全性和耐受性：一项随机，3期，双盲，安慰剂对照试验。

背景

Rimegepant是一种降钙素基因相关的小分子肽受体拮抗剂，在使用标准片剂配制的偏头痛急性治疗中已显示出疗效。这项试验的目的是比较一种新型的rimegepant口服崩解片与安慰剂的75 mg口服制剂在急性偏头痛治疗中的功效，安全性和耐受性。

方法

在这项双盲，随机，安慰剂对照，多中心3期试验中，年龄18岁或以上且偏头痛病史至少为1年的成年人被招募到美国的69个研究中心。参与者被随机分配接受瑞格非特（75 mg口腔崩解片）或安慰剂，并被指示治疗中度或重度疼痛强度的单次偏头痛发作。通过使用预防性药物（是或否）对随机分组进行分层，并使用每个临床站点均可访问的交互式网络响应系统进行随机分组。所有参与者，研究者和申办者都被掩盖在治疗组分配中。共同的主要终点是服药后2小时无疼痛和无最症状。功效分析使用改良的意向性治疗人群，包括所有被随机分配，偏头痛发作，中度或重度疼痛，服用了瑞吉明或安慰剂的患者，并在给药后进行了至少一项疗效评估。安全性分析包括所有接受至少一剂研究药物的随机分配的参与者。这项研究已向，编号注册，并且不予计入。

发现

在2018年2月27日至8月28日之间，招募了1811名参与者并评估了他们的资格。将1466名参与者随机分配至瑞吉普特（n = 732）或安慰剂（n = 734）组，其中1375名接受瑞吉普特（n = 682）或安慰剂（n = 693）的治疗，并评估1351的疗效（瑞吉普特） n = 669，安慰剂n = 682）。给药后2小时，瑞吉美特口腔崩解片在疼痛方面的耐受性优于安慰剂（21％vs 11％，p <0·0001；风险差异为10，95 ％CI 6-14），并且没有最麻烦的症状（35）。 ％vs27％，p = 0·0009；风险差异为8，95％CI 3-13）。最常见的不良事件是恶心（瑞吉普特n = 11 [2％]；安慰剂n = 3 [<1％]）和尿路感染（瑞吉普特n = 10 [1％]；安慰剂n = 4 [1％]） 。每个治疗组中的一名参与者的转氨酶浓度高于正常值上限的3倍。两者均与研究用药无关，并且未报告胆红素升高超过正常值上限的2倍。接受治疗的参与者报告无严重不良事件。

解释

在偏头痛的急性治疗中，口服崩解片配方中的75mg瑞格明单剂量比安慰剂更有效。耐受性类似于安慰剂，没有安全隐患。

资金

Biohaven制药。