Ubrogepant Mitigates Early Migraine Symptoms When Taken During Prodrome: Study
Researchers have determined in a recent study that increasing ubrogepant during the prodromal phase of a migraine relieves early signs considerably and decreases the chances of evolving into a full-blown headache. PRODROME trial is a phase 3, randomized, double-blind, placebo-controlled crossover trial that assessed the efficacy of ubrogepant 100 mg, a calcitonin gene-related peptide (CGRP) receptor antagonist, when administered during the premonitory phase of migraine attacks. The trial proved that early intervention not only alleviated typical prodromal symptoms like photophobia, fatigue, and neck pain but also enhanced cognition and general patient-reported outcomes. The study was published in the Nature Medicine journal by Peter J. and colleagues.
The PRODROME trial enrolled 477 participants across 75 research centers in the United States. Eligible participants were adults aged 18–75 years with a history of migraine with or without aura, experiencing two to eight migraine attacks per month. Participants were instructed to take a 100 mg dose of ubrogepant or placebo during the prodromal phase, defined as the period 1–6 hours before the anticipated onset of headache—based on their recognition of prodromal symptoms. The research utilized a crossover design, where every participant was administered ubrogepant and placebo treatments for distinct qualifying prodromal events. Results were measured over 48 hours after each treatment.
Key Findings
The findings of the trial were that ubrogepant hugely showed improvement in various prodromal symptoms than that of the placebo:
Photophobia (light sensitivity): 19.5% of the ubrogepant-treated events reported absence of photophobia at 2 hours post-dose, vs. 12.5% with placebo (OR = 1.72; 95% CI: 1.13–2.61).
Fatigue: Absence of fatigue at 3 hours post-dose was seen in 27.3% of ubrogepant-treated events vs. 16.8% with placebo (OR = 1.85; 95% CI: 1.17–2.92).
Neck Pain: No neck pain at 3 hours post-dose occurred in 28.9% of ubrogepant-treated events, versus 15.9% with placebo (OR = 2.04; 95% CI: 1.25–3.32).
Phonophobia (sound sensitivity): No phonophobia at 4 hours post-dose was seen in 50.7% of ubrogepant-treated events, versus 35.8% with placebo (OR = 1.97; 95% CI: 1.38–2.80).
Dizziness: The no dizziness response was achieved by 88.5% of ubrogepant-treated events at 24 hours post-dose compared to 82.3% with placebo (OR = 1.82; 95% CI: 1.00–3.30).
Cognitive Symptoms: Cognitive improvement was reported, with 8.7% of ubrogepant-treated events reporting no difficulty concentrating at 1 hour post-dose, versus 2.1% with placebo (OR = 4.26; 95% CI: 1.17–15.54). Moreover, at 6 hours post-dose, 56.9% of ubrogepant-treated events reported no difficulty thinking, compared to 41.8% with placebo (OR = 2.05; 95% CI: 1.14–3.71).
In addition, the research revealed that 46% of ubrogepant-treated prodromal episodes failed to evolve to moderate or severe headache within 24 hours, in contrast to 29% with placebo (OR = 2.09; 95% CI: 1.63–2.69; p < 0.0001).
Patient-Reported Outcomes
In addition to relief from symptoms, ubrogepant proved dramatic gains in patient-reported functional outcomes:
Functional Ability: More ubrogepant-treated participants reported "no disability, able to function normally" at 2 hours post-dose than placebo (OR = 1.76; 95% CI: 1.32–2.35; p = 0.0001).
Activity Limitations: Within 24 hours, ubrogepant-treated participants showed a significant decrease in activity limitations (OR = 2.07; 95% CI: 1.61–2.67; p < 0.0001).
PRODROME trial demonstrates strong evidence that ubrogepant, taken at the prodromal phase of a migraine, can significantly alleviate initial symptoms and prevent escalation to more intense headache stages. These findings highlight the value of ubrogepant as a successful early intervention technique for patients able to identify their prodromal symptoms reliably, providing a proactive strategy for managing migraine.
Reference:
Goadsby, P.J., Ailani, J., Dodick, D.W. et al. Ubrogepant for the treatment of migraine prodromal symptoms: an exploratory analysis from the randomized phase 3 PRODROME trial. Nat Med (2025). https://doi.org/10.1038/s41591-025-03679-7
