Ubrogepant Taken During Migraine Prodrome Reduces Headache Severity: Phase 3 Clinical Trial

Full findings from the phase 3 PRODROME study (NCT04492020) of ubrogepant (Ubrelvy; AbbVie) have been announced and published in The Lancet, demonstrating a positive impact of the oral calcitonin gene-related peptide inhibitor on migraine symptoms during the prodrome phase, according to a statement from the manufacturer.¹

^{David W Dodick, MD (courtesy of Atria Institute)}

Led by David W Dodick, MD, professor of neurology at Mayo Clinic Scottsdale, PRODROME was the first large placebo-controlled trial evaluating the efficacy of an acute treatment administered during the prodromal period.¹ At the conclusion of the trial, absence of moderate or severe headache within 24 hours after initiating treatment occurred in 46% (190 of 418) of qualifying prodrome events that had been treated with ubrogepant compared with 29% (121 of 423) of events treated with placebo (OR, 2.09; 95% CI, 1.63-2.69; P <.001).²

"As a neurologist, I have many patients who can describe the premonitory, or prodrome, symptoms of their migraine attacks, and previously we have not had adequate data for treatment options during this earliest phase,” Peter J Goadsby, MD, PhD, FRS, neurologist and professor at King’s College London, said in the statement.¹ "These new data speak directly to a gap in migraine treatment and the option to use ubrogepant."

Conducted between April 2020 and April 2022, 518 participants aged 18-75 years with at least a 1-year history of migraine with or without aura were randomly assigned to double-blind crossover treatment.² Patients were split 1:1 to either placebo to treat the first qualifying prodrome event and ubrogepant 100 mg to treat the second qualifying prodrome event or to receive ubrogepant 100 mg to treat the first qualifying prodrome event and placebo to treat the second. Research staff who administered interventions and those how assessed outcomes were masked to group assignment during the study.² The absence of a headache of moderate or severe intensity within 24 hours of treatment was the primary endpoint.

The safety population included 480 participants and the modified intent-to-treat (mITT) population included 477 participants; the majority (88%) were women. Participants underwent a 60-day screening period followed by the 60-day double-blind portion. In total, 85% (n = 438) of the total cohort completed the trial, with failure to treat 2 qualifying prodrome events (10%) within 60 days as the most common reason for discontinuation.

FINDINGS

Within 48 hours after initiating treatment, the absence of moderate or severe headache was achieved in 41% (159 of 391) of qualifying prodrome events treated with ubrogepant 100 mg vs 25% (100 of 407) of qualifying prodrome events that were treated with placebo (OR, 2.13; 95% CI, 1.63-2.78; P <.001). During 24 hours after treatment, more participants reported “no disability, able to function normally,” status after a prodrome event with ubrogepant 100 mg vs those on placebo (OR, 1.66; 95% CI, 1.40-1.96; P <.001).

"Migraine impacts nearly 40 million Americans and is a highly debilitating disease that can cause people to miss work, and time with friends and family," Dawn Carlson, vice president of Neuroscience Development at AbbVie, said.¹ "For patients who are able to identify prodromal symptoms, the ability to treat a migraine attack before the headache phase creates an opportunity to stop migraine attacks before they become fully debilitating."¹

Between the 2 groups, adverse events (AEs) occurring 48 hours after study-drug administration were found in 17% and 12% of qualifying prodrome events for those treated with ubrogepant and placebo, respectively. Nausea (ubrogepant: 5%; placebo: 3%), fatigue (3% vs 2%), dizziness (2% vs 3%), and somnolence (2% vs 11%) were reported as the most common AEs observed.

This study review originally appeared on our partner site NeurologyLive.®

References
1. Results published in The Lancet show Ubrelvy (ubrogepant) reduces the headache phase of a migraine attack when dosed during the prodrome of migraine. News release. AbbVie. November 16, 2023. Accessed November 17, 2023. https://www.prnewswire.com/news-releases/results-published-in-the-lancet-show-ubrelvy-ubrogepant-reduces-the-headache-phase-of-a-migraine-attack-when-dosed-during-the-prodrome-of-migraine-
2. Dodick DW, Goadsby PJ, Schwedt TJ, et al. Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3 multicentre, randomized, double-blind, placebo-controlled, crossover trial in the USA. The Lancet. Published online November 15, 2023. doi:10.1016/S0140-6736(23)01683-5