Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial.

Abstract

BACKGROUND\nAtogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of migraine.\n\n\nMETHODS\nIn the double-blind, phase 3 ADVANCE trial, participants with 4-14 migraine days/month were randomized to atogepant 10\u2009mg, 30\u2009mg, 60\u2009mg, or placebo once daily for 12 weeks. We evaluated the time course of efficacy of atogepant for the preventive treatment of migraine. Analyses included change from baseline in mean monthly migraine days during each of the three 4-week treatment periods, change in weekly migraine days during weeks 1-4, and proportion of participants with a migraine on each day during the first week.\n\n\nRESULTS\nWe analyzed 873 participants (n\u2009=\u2009214 atogepant 10\u2009mg, n\u2009=\u2009223 atogepant 30\u2009mg, n\u2009=\u2009222 atogepant 60\u2009mg, n\u2009=\u2009214 placebo). For weeks 1-4, mean change from baseline in mean monthly migraine days ranged from -3.1 to -3.9 across atogepant doses vs -1.6 for placebo (p\u2009<\u20090.0001). For weeks 5-8 and 9-12, reductions in mean monthly migraine days ranged from -3.7 to -4.2 for atogepant vs -2.9 for placebo (p\u2009≤\u20090.012) and -4.2 to -4.4 for atogepant vs -3.0 for placebo (p\u2009<\u20090.0002), respectively. Mean change from baseline in weekly migraine days in week 1 ranged from -0.77 to -1.03 for atogepant vs -0.29 with placebo (p\u2009<\u20090.0001). Percentages of participants reporting a migraine on post-dose day 1 ranged from 10.8% to 14.1% for atogepant vs 25.2% with placebo (p\u2009≤\u20090.0071).\n\n\nCONCLUSION\nAtogepant demonstrated treatment benefits as early as the first full day after treatment initiation, and sustained efficacy across each 4-week interval during the 12-week treatment period.Clinical trial registration: ClinicalTrials.gov identifier: NCT03777059.