Efficacy of Ubrogepant for the Treatment of Migraine Symptoms During the Prodrome (Premonitory Phase): Results From the PRODROME Trial

Efficacy of Ubrogepant for the Treatment of Migraine Symptoms During the Prodrome (Premonitory Phase): Results From the PRODROME Trial

Background: Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine.

Purpose/Objectives: To evaluate the efficacy of ubrogepant 100 mg to treat migraine symptoms during the prodrome (premonitory phase). The primary objective of the PRODROME trial was to evaluate the efficacy of ubrogepant to prevent or attenuate headache following administration during the prodrome. Additionally, the study rigorously assessed the effect of ubrogepant on prodromal symptoms.

Method:

PRODROME (NCT04492020) was a multicenter, randomized, double-blind, placebo-controlled, crossover trial that enrolled adults who experienced 2­8 migraine attacks with moderate-to-severe headache per month. 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. Participants used an e-diary to record the presence and severity of symptoms at the time of each qualifying prodrome event. We report the frequency and severity of common prodromal symptoms and the presence/absence of these symptoms over 48 hours post-dose.

Results: During the double-blind treatment period, the most common prodromal symptoms reported prior to study drug administration were (ubrogepant-treated and placebo-treated events, respectively) sensitivity to light (60.9% and 60.8%), fatigue (50.7% and 50.3%), neck pain (40.2% and 40.1%), sensitivity to sound (35.9% and 36.1%), and dizziness (29.0% and 31.0%). Between 30.8% and 57.2% of these symptoms were moderate or severe in intensity. The proportion of events with absence of sensitivity to light after ubrogepant 100 mg was numerically greater than after placebo, starting 2 hours post-dose and extending through 48 hours (nominal P≤0.0109 for hours 2-8). Similar results were observed for the other common symptoms. Time to absence of each individual prodromal symptom was shorter after treatment with ubrogepant than after placebo.

Conclusions: Treatment with ubrogepant 100 mg during the prodrome improved the common migraine prodromal symptoms compared with placebo.

References: 1. Headache Classification Committee of the International Headache Society.
Cephalalgia. 2018;38:1-211.
2. Ubrelvy [package insert]. AbbVie; 2023.
3. Navratilova E, et al. Cephalalgia. 2020;40:892-902.