Time Course of Rimegepant Effect for Acute Treatment of Migraine in Adults Unsuitable for Triptans: Exploratory Endpoints from a Phase 4, Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION

A recent placebo-controlled trial (NCT05509400) demonstrated efficacy of single-dose rimegepant 75 mg for acute treatment of migraine in adults unsuitable for triptans. However, the full time course of rimegepant effect has not been reported for this study population.

METHODS

Pre-specified exploratory endpoints from study NCT05509400 assessed the percentage of participants with migraine pain relief, migraine pain freedom, return to normal function, and most bothersome symptom (MBS; nausea, photophobia, or phonophobia) freedom from 15 min to 48 h post-dose. Treatment comparisons used crude risk estimation with nominal p values.

RESULTS

Participants (rimegepant n = 286; placebo n = 284) were mostly female (89.3%) and had documented failure to ≥ 2 triptans with ≥ 1 reason due to prior intolerance (30.5%) or lack of efficacy (84.9%); 9.1% had a contraindication. Improvements of ≥ 5% for rimegepant over placebo with p ≤ 0.05 [difference (95% CI)] were first observed at 1 h for pain relief [8.6% (1.3%, 15.8%); p = 0.0201], 1.5 h for pain freedom [6.2% (1.5%, 11.0%); p = 0.0103] and return to normal function [7.1% (1.1%, 13.1%); p = 0.0210], and 2 h for MBS freedom [12.5% (5.4%, 19.5%); p = 0.0005]. Improvements of ≥ 5% over placebo were observed at all subsequent time points. Differences (95% CI) at 48 h were 31.2% (23.5%, 39.0%; p < 0.0001) for pain relief, 33.4% (25.9%, 40.9%; p < 0.0001) for pain freedom, 34.1% (25.8%, 42.5%; p < 0.0001) for return to normal function, and 23.2% (15.5%, 31.0%; p < 0.0001) for MBS freedom.

CONCLUSION

In some patients unsuitable for triptans, rimegepant can provide rapid onset (within 1-2 h) of migraine symptom improvement. Improvements may be observed up to 48 h. Rimegepant may be appropriate when triptans are not suitable, particularly in individuals who failed triptans previously due to lack of efficacy. Graphical abstract available for this article.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT05509400.