Ubrogepant for the Acute Treatment of Migraine When Administered During the Prodrome (Premonitory Phase): Results From a Phase 3, Randomized, Double-blind, Placebo-Controlled, Crossover Study
David W. Dodick1, Peter J. Goadsby2, Todd J. Schwedt1, Richard B. Lipton3, Chengcheng Liu4, Kaifeng Lu4, Sung Yun Yu4, Lawrence Severt4, Michelle Finnegan4, Joel M. Trugman4
1Mayo Clinic, 2King's College and University of California Los Angeles, 3Albert Einstein College of Medicine, 4AbbVie
Objective:
To evaluate the efficacy, safety, and tolerability of ubrogepant 100 mg when administered during the prodrome (premonitory phase) of a migraine attack.
Background:
Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine. The prodrome is the earliest phase of the migraine attack and is characterized by symptoms other than aura, which precede onset of headache. This study examined the potential of ubrogepant, when administered during the prodrome, to prevent or attenuate headache and disability.
Design/Methods:
PRODROME (NCT04492020) was a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Eligible participants treated 2 “qualifying prodrome events,” defined as a migraine attack with prodromal symptoms in which the participant was confident a headache would follow within 1-6 hours. The primary endpoint was absence of moderate/severe intensity headache within 24 hours post-dose. Secondary endpoints were absence of moderate/severe intensity headache within 48 hours, ability to function normally over 24 hours, and absence of a headache of any intensity within 24 hours post-dose.
Results:
The safety population included 480 participants and the modified intent-to-treat population included 477 participants. The absence of moderate/severe intensity headache within 24 hours was achieved following 45.5% of ubrogepant-treated qualifying prodrome events vs 28.6% of placebo-treated events (P<0.0001). Absence of moderate/severe intensity headache within 48 hours (40.7% vs 24.6%; P<0.0001), ability to function normally over 24 hours (OR=1.66; P<0.0001), and absence of headache of any intensity within 24 hours (23.7% vs 13.9%; P<0.0001) were achieved at significantly greater rates following ubrogepant-treated events vs placebo. Ubrogepant was well-tolerated with no new safety signals observed when administered during the prodrome.
Conclusions:
Treatment with ubrogepant 100 mg during the prodrome prevented the development of moderate/severe headache for 24 and 48 hours post-dose and headache of any intensity within 24 hours and reduced functional disability compared with treatment with placebo.