Phase 3 PRODROME Study Highlights Ubrogepant’s Impact on Migraine Prior to Attacks


Compared with placebo, treatment with ubrogepant 100 mg during the prodrome significantly reduced the development of moderate or severe headache for 24 hours after study-drug dose.

David W. Dodick, MD

David W. Dodick, MD

After the initial data was presented earlier this year, investigators have published full findings of the phase 3 PRODROME study (NCT04492020) demonstrating ubrogepant’s (Ubrelvy; AbbVie) positive impact on migraine during the prodrome phase in The Lancet.

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 prodrome. 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 <.0001).

"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 a 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 1-year history of migraine with or without aura were randomly assigned to double-blind crossover treatment. 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. Those who gave interventions and assessed outcomes were masked to group assignment during the study.

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

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 <.0001). During 24 hours after treatment, more participants had “no disability, able to function normally,” status after a prodrome event with ubrogepant 100 mg than on placebo (OR, 1.66; 95% CI, 1.40-1.96; P <.0001).

"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. 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," Dawn Carlson, vice president of Neuroscience Development at AbbVie, said in a statement.1 "These data published in The Lancet demonstrate the important role of UBRELVY in treating migraine attacks early and reducing the overall burden of a migraine attack."

Between the 2 groups, adverse events (AEs) occurring 48 hours after study-drug administration were found in 17% (77 of 456) and 12% (55 of 462) of qualifying prodrome events for those treated with ubrogepant and placebo, respectively. In the study, 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.

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.
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
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