Pfizer Internal Medicine
This Phase 4, randomized, double blind, placebo controlled trial evaluated the efficacy and safety of a single 75 mg dose of rimegepant orally disintegrating tablet (ODT) for the acute treatment of migraine in adults who are unsuitable for triptans. Unsuitability was defined as prior lack of efficacy and/or intolerance to at least two triptans, or a documented medical contraindication to triptan use. Adults aged 18 years or older with a ≥ 1 year history of migraine and 4–14 migraine days per month were randomized to receive a single dose of rimegepant 75 mg or placebo to treat one migraine attack of moderate or severe pain intensity. The primary endpoint was migraine pain relief (headache pain intensity of none or mild) at 2 hours after dosing. Key secondary endpoints included pain freedom at 2 hours, freedom from the most bothersome symptom, return to normal function, sustained pain relief, and use of rescue medication.
Rimegepant demonstrated statistically significant and clinically meaningful improvements compared with placebo across the primary endpoint and all key secondary endpoints. Safety outcomes were similar between treatment groups, with no severe or serious adverse events reported in the rimegepant group.
Details of these and other results, including time-course data and open-label extension data, are provided below.
A subset of individuals with migraine are unable to use triptans because these medicines do not work well for them, cause intolerable side effects, or are contraindicated due to cardiovascular or other medical conditions. Until recently, there has been limited randomized clinical trial evidence specifically evaluating acute migraine treatments in this triptan unsuitable population.
This study is important because it is the first prospective, randomized trial to demonstrate that a calcitonin gene related peptide (CGRP) receptor antagonist, rimegepant, is effective for the acute treatment of migraine in adults who cannot use triptans. The primary endpoint—migraine pain relief at 2 hours—was achieved by 55.9% of participants treated with rimegepant compared with 32.7% of those receiving placebo, representing a statistically significant difference (23.2%, p<0.0001).
In addition to pain relief at 2 hours, rimegepant showed benefits across multiple functional and symptom-based outcomes at time points between 2 hours and 48 hours, while maintaining a safety profile similar to placebo. Together, these findings support rimegepant 75 mg as an acute treatment option in adults who are unsuitable for triptans.
References: Ashina M, McAllister P, Gaul C, et al. Rimegepant for acute treatment of migraine in triptan unsuitable adults: A randomized, double-blind, placebo-controlled phase 4 trial. Cephalalgia. 2025 Nov;45(11):3331024251395298. doi: 10.1177/03331024251395298. Epub 2025 Nov 18.
EM-GLB-RMGP-0090 | March 2026 Page published: 11-April-2026
[Nov-2025] A randomized, double-blind, placebo-controlled phase 4 trial evaluating a single dose of rimegepant 75 mg for the acute treatment of migraine in...
