Efficacy and safety of rimegepant for the preventive treatment of migraine in Japan: A double-blind, randomized controlled trial.

Objectives/background: This study was undertaken to compare the efficacy of the oral calcitonin gene-related peptide receptor antagonist rimegepant relative to placebo as a preventive treatment for migraine in Japan. This was the first randomized placebo-controlled trial of rimegepant for the preventive treatment of migraine to be conducted outside the United States and the second conducted globally.

Methods: In this phase 3, double-blind, randomized, multicenter trial, conducted August 9, 2022 through January 18, 2024, adults in Japan with a history of 4-18 migraine attacks/month of moderate or severe pain intensity completed a 28-day observation phase and then took rimegepant 75 mg or placebo every other day during the 12-week double-blind treatment phase. The primary endpoint was the mean change from the observation phase in the number of monthly migraine days in the last 4 weeks of the double-blind treatment phase. Safety was assessed based on the frequency of adverse events and laboratory test abnormalities during the double-blind treatment phase.

Results: A total of 484 (efficacy) and 496 (safety) treated participants were evaluable. During the observation phase, participants in the rimegepant and placebo groups, respectively, reported a mean (SD) of 9.3 (3.1) and 9.0 (3.1) monthly migraine days. The study met its primary endpoint with a statistically significant difference in mean change from the observation phase in the number of monthly migraine days in the last 4 weeks of the double-blind treatment phase (difference rimegepant vs. placebo: -1.1 [95% confidence interval = -1.73 to -0.38], p = 0.002). In the rimegepant and placebo groups, respectively, 54.7% and 41.0% of participants reported adverse events and 0.8% and 0.4% reported serious adverse events during the double-blind treatment phase. No signal of drug-induced liver injury due to rimegepant was identified.

Conclusion: Rimegepant 75 mg every other day demonstrated efficacy superior to that of placebo for the preventive treatment of migraine, with a favorable safety profile. NCT05399485.

Plain language summary: This study tested the effectiveness of rimegepant for migraine prevention in Japan. Results showed that rimegepant was more effective than placebo in reducing monthly migraine days, with very few adverse effects. These results support the previous findings from a clinical study conducted in the United States and broaden them to a wider population.