To evaluate the time course of effectiveness of 2 rimegepant (RIM) regimens for the preventive treatment of episodic migraine.

This was a phase 4, randomized, double-blind study evaluating the efficacy and safety of 2 RIM 75-mg dosing regimens (every other day [EOD] and once daily [QD]) vs placebo (PBO).

A 28-day observation phase (OP) was followed by randomization to RIM 75 mg EOD/alternating PBO, RIM 75 mg QD, or PBO QD for a 12-week double-blind treatment (DBT) phase followed by a 12-week open-label (RIM 75 mg QD) phase. Prespecified exploratory endpoints through the DBT phase included change from the OP in the number of weekly migraine days and monthly migraine days (MMDs) and the proportion of participants with ≥50% reductions in weekly migraine days and MMDs.

692 participants were treated with double-blind study drug. For the RIM EOD, RIM QD, and PBO groups, respectively, mean (97.5% CI) changes in weekly migraine days were -0.6 (-0.83, -0.40), -1.0 (-1.17, -0.78), and -0.2 (-0.44, -0.03) in Week 1, and changes in MMDs were -2.6 (-3.15, -2.05), -3.5 (-4.00, -2.96), and -1.5 (-2.00, -1.06) in Month 1, and -3.1 (-3.70, -2.53), -4.1 (-4.65, -3.54), and -2.9 (-3.45, -2.37) in Month 3. For the RIM EOD, RIM QD, and PBO groups, respectively, 42.4% (p=0.0088 vs PBO), 55.1% (p<0.0001 vs PBO), and 29.9% of participants had ≥50% reduction in weekly migraine days in Week 1; 34.8% (p=0.0052 vs PBO), 49.1% (p<0.0001 vs PBO), and 23.2% (Month 1), and 42.5% (p=0.2982 vs PBO), 55.0% (p=0.0003 vs PBO), and 37.9% (Month 3) of participants, respectively, had ≥50% reduction in MMDs. Both regimens were well tolerated.

Both RIM regimens were effective for the preventive treatment of migraine within the first week with efficacy generally maintained through 12 weeks. Clinicaltrials.gov NCT05217927. Funded by Pfizer.