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.

BACKGROUND

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.

METHODS

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.

FINDINGS

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<0·0001) and freedom from the most bothersome symptom (336 [50%] of 666 participants vs 241 [36%] of 674 participants, 14·8, 9·6-20·0; p<0·0001). The most common (≥1%) adverse events were protein in urine (8 [1%] of 668 participants in the rimepegant group vs 7 [1%] of 674 participants in the placebo group), nausea (7 [1%] of 668 vs 18 [3%] of 674), and urinary tract infection (5 [1%] of 668 vs 8 [1%] of 674). There were no rimegepant-related serious adverse events.

INTERPRETATION

Among adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population.

FUNDING

BioShin Limited.

TRANSLATIONS

For the Chinese and Korean translations of the abstract see Supplementary Materials section.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests B-KK has received personal compensation for serving on a scientific advisory board for Lundbeck Korea, Pfizer Korea, and Novartis; he has received personal compensation for serving as a speaker or moderator for Allergan Korea, Lilly Korea, Teva Korea, GSK Korea, Lundbeck Korea, and SK-Pharma. M-HK has received personal compensation for serving on a scientific advisory board for Lundbeck Korea, Novartis, Allergan Korea, Lilly Korea, and Teva Korea. H-SM was a principal investigator for a multicentre trial sponsored by Lundbeck, Novartis, and Eli Lilly; she received lecture honoraria from GSK Korea, SK Pharma, Teva Korea, Lundbeck Korea, Allergan Korea, and Yuyu Pharma in the past 24 months. DM, MH, DAS, and RC were employed by Biohaven Pharmaceuticals, the developer of rimegepant, during the trial. RC and ZL are currently employed by Pfizer, the development and commercial rights owner of rimegepant. YG and ZL were employed by BioShin Limited, the trial sponsor, during the conduct of the trial. SY, AG, MZ, ZW, JL, GT, and QY declare no competing interests