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

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

Background: Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine. The prodrome (premonitory phase) is the earliest phase of the migraine attack.

Purpose/Objectives: To evaluate the efficacy, safety, and tolerability of ubrogepant 100 mg when administered during the prodrome (premonitory phase) of a migraine attack. This study examined the potential of ubrogepant, when administered during the prodrome, to prevent or attenuate headache and disability.

Method:

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.

References: AHS Consensus Statement. Headache. 2021;61:1021-1039.

Ubrelvy [package insert]. Allergan USA; 2021.

Ubrelvy [product monograph]. AbbVie Canada; 2022.

Dodick DW, et al. 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. Abstract presented at AAN 2023.