Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial

• Published in: Lancet neurology 2023-06, Vol.22 (6), p.476-484
• Main Authors: Yu, Shengyuan, Kim, Byung-Kun, Guo, Aihong, Kim, Man-Ho, Zhang, Mingjie, Wang, Zhen, Liu, Jianguang, Moon, Heui-Soo, Tan, Ge, Yang, Qian, McGrath, Donnie, Hanna, Michael, Stock, David A, Gao, Yanfei, Croop, Robert, Lu, Zhihong
• Format: Article
• Language: English
• Subjects: Adult; Adverse events; Analgesics; Calcitonin; Calcitonin Gene-Related Peptide; Cardiovascular disease; China; Clinical trials; Coronary vessels; Disease prevention; Dosage; Double-Blind Method; Double-blind studies; Drug dosages; FDA approval; Headache; Headaches; Herbal medicine; Humans; Ischemia; Migraine; Migraine Disorders - diagnosis; Nausea; Nonsteroidal anti-inflammatory drugs; Oral administration; Pain; Placebos; Prescription drugs; Quality of life; Safety; Substance abuse treatment; Tablets - therapeutic use; Treatment Outcome; Urinary tract
• ISSN: 1474-4422; 1474-4465
• DOI: 10.1016/S1474-4422(23)00126-6

No acute treatments targeting calcitonin gene-related peptide (CGRP) have been approved for use in China or South Korea. We aimed to compare the efficacy and safety of rimegepant—an orally administered small molecule CGRP antagonist—with placebo in the acute treatment of migraine among adults in these countries. This double-blind, randomised, placebo-controlled, multicentre phase 3 trial was done at 86 outpatient clinics at hospitals and academic medical centres (73 in China and 13 in South Korea). Participants were adults (≥18 years) with at least a 1-year history of migraine who had two to eight moderate or severe attacks per month and fewer than 15 headache days per month within the 3 months before the screening visit. Participants were randomly assigned (1:1) to 75 mg rimegepant or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use of preventive medication and by country. The allocation sequence was generated and implemented by study personnel using an interactive web-response system accessed online from each study centre. All participants, investigators, and the sponsor were masked to treatment assignment. The coprimary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, phonophobia, or photophobia) 2 h after dosing were assessed in the modified intention-to-treat (mITT) population (randomly assigned participants who took study medication for a migraine attack of moderate or severe pain intensity, and provided at least one efficacy datapoint after treatment) using Cochran-Mantel Haenszel tests. Safety was assessed in all participants who received rimegepant or placebo. The study is registered with ClinicalTrials.gov, number NCT04574362, and is completed. 1431 participants were randomly assigned (716 [50%] to rimegepant and 715 [50%] to placebo). 668 (93%) participants in the rimegepant group and 674 (94%) participants in the placebo group received treatment. 1340 participants were included in the mITT analysis (666 [93%] in the rimegepant group and 674 [94%] in the placebo group). 2 h after dosing, rimegepant was superior to placebo for pain freedom (132 [20%] of 666 vs 72 [11%] of 674, risk difference 9·2, 95% CI 5·4–13·0; p