Abstract text (incl. figure legends and references)

Objective: To evaluate impact of atogepant (ATO) on key secondary and exploratory patient-reported outcomes (PROs) for measures of functioning and headache-related impact among individuals with CM.

Methods: Phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled trial. Participants with ≥1-year history of CM, ≥15 headache d/mo in the past 3 months, and ≥15 headache days (with ≥8 days qualifying as migraine days) during the 28-day screening period were randomized to receive ATO 30mg twice daily (BID), ATO 60mg once daily (QD), or PBO during the 12-week treatment period. PROs included the Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ) and Headache Impact Test-6 (HIT-6). Change from baseline in MSQ Role Function-Restrictive (RFR) domain and HIT-6 scores at week 12 were key secondary endpoints in Europe and Canada (MSQ RFR was also a key secondary endpoint in the United States). A graphical approach with weighted Bonferroni test procedure was used to control the overall type I error rate at the two-sided α=.05 level for key secondary endpoints. For exploratory endpoints, nominal P values were provided without adjusting for multiplicity.

Results: Of 778 participants randomized, 773 received study drug (mean age: 42.1y; 87.6% female), and 755 were included in the modified intent-to-treat population (ATO 30mg BID, n=253; ATO 60mg QD, n=256; PBO, n=246). At all assessed timepoints, increases from baseline (improvements) in all MSQ domain scores were significantly greater in both ATO doses vs PBO (P<.01) (Figure). Both doses demonstrated significant improvement in HIT-6 scores vs PBO at all assessed time points (P<.001). Significantly greater proportions of ATO- vs PBO-treated participants were HIT-6 responders (reduction ≥5 points) at all time points and doses (nominal P<.001).

Conclusions: ATO demonstrated statistically significant improvements in PRO measures of functional ability and impact of headache.