美国Biohaven制药Robert Croop研究小组近日取得一项新成果。他们分析了Rimegepant口服崩解片治疗偏头痛的疗效、安全性和耐受性。 相关论文发表在2019年8月30日出版的《柳叶刀》杂志上。

在这项双盲、随机、安慰剂对照、多中心的临床3期试验中，2018年2月27日至8月28日，美国69个研究中心招募了1466名18岁及以上且至少有1年偏头痛史的成年人。732名被随机分配口服Rimegepant崩解片75毫克，最终有669名接受疗效评估，734名被随机分配服用安慰剂，最终有682名接受了疗效评估。

服药后2小时，Rimegepant崩解片的止痛效果显著优于安慰剂（21% vs 11%），且没有最反感的症状（35% vs 27%）。最常见的不良反应为恶心，其中Rimegepant组有11例（2%），安慰剂组有3例（< 1%）；以及尿路感染，其中Rimegepant组有10例（1%），安慰剂组有4例（1%）。每组中都有一名患者转氨酶浓度超过正常上限三倍以上，但均与药物治疗无关。两组均未发生胆红素升高超正常上限两倍，亦未发生严重不良事件。

综上，单独口服Rimegepant崩解片75毫克对偏头痛进行急性治疗比安慰剂更有效，患者可耐受，安全性高，值得临床推广。

据悉，Rimegepant是一种小分子降钙素基因相关肽受体拮抗剂，治疗急性偏头痛已初见成效。

附：英文原文

Title: Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial

Author: Robert Croop, Peter J Goadsby, David A Stock, Charles M Conway, Micaela Forshaw, Elyse G Stock, Vladimir Coric, Richard B Lipton

Issue&Volume: Volume 394 Number 10200,30 August 2019

Summary: 

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 ClinicalTrials.gov, number NCT03461757, 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.

DOI: https://doi.org/10.1016/S0140-6736(19)31606-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31606-X/fulltext