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Randomized Controlled Trial
. 2024 Sep 24;103(6):e209745.
doi: 10.1212/WNL.0000000000209745. Epub 2024 Aug 28.

Effect of Ubrogepant on Patient-Reported Outcomes When Administered During the Migraine Prodrome: Results From the Randomized PRODROME Trial

Richard B Lipton  1 , Andrea M Harriott  1 , Julia Y Ma  1 , Jonathan H Smith  1 , Jonathan Stokes  1 , Pranav Gandhi  1 , Krutika Jariwala-Parikh  1 , Gabriel S Jensen  1 , Joel M Trugman  1 , David W Dodick  1
Affiliations
Randomized Controlled Trial

Effect of Ubrogepant on Patient-Reported Outcomes When Administered During the Migraine Prodrome: Results From the Randomized PRODROME Trial

Richard B Lipton et al. Neurology. .

Abstract

Background and objectives: Ubrogepant is a calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. The PRODROME trial previously demonstrated that ubrogepant treatment during prodrome prevents the onset of moderate or severe headache. In this analysis of the PRODROME trial, the benefits of ubrogepant treatment during the prodrome on patient-reported outcomes (PROs) are evaluated.

Methods: PRODROME was a multicenter, randomized, double-blind, placebo-controlled, crossover trial that enrolled adults who experienced 2-8 migraine attacks per month with moderate-severe headache pain. Eligible participants treated 2 qualifying prodrome events, defined as a migraine attack with prodromal symptoms when the participant was confident a headache would follow within 1-6 hours. Participants were randomized to treatment sequence A (placebo then ubrogepant 100 mg) or sequence B (ubrogepant 100 mg then placebo). This analysis evaluated the ability to function normally over 24 hours (secondary end point) and at specific time points after dose (additional end point). Other PRO end points included activity limitation over 24 hours and satisfaction with study medication at 8 and 24 hours.

Results: Of 518 randomized participants, 477 comprised the modified intent-to-treat population. After treatment of qualifying prodrome events, a significantly greater ability to function normally over 24 hours was observed for participants after treatment with ubrogepant 100 mg compared with placebo (odds ratio [OR] 1.66, 95% CI 1.40-1.96; p < 0.0001). As early as 2 hours after dose, a greater proportion of ubrogepant-treated participants reported "no disability, able to function normally" compared with placebo (OR 1.76, 95% CI 1.32-2.35; nominal p = 0.0001). Ubrogepant administered during the prodrome was also associated with a greater reduction in activity limitations over 24 hours after dose (OR 2.07, 95% CI 1.61-2.67; nominal p < 0.0001). At 8 and 24 hours after dose, rates of being "satisfied" or "extremely satisfied" were greater for ubrogepant than for placebo (8 hours: OR 2.37, 95% CI 1.78-3.15; nominal p < 0.0001; 24 hours: OR 2.32, 95% CI 1.78-3.02; nominal p < 0.0001).

Discussion: Ubrogepant 100 mg administered during the prodrome was associated with significantly greater ability to function normally, greater reduction in activity limitations over 24 hours, and greater satisfaction with study medication, compared with placebo.

Trial registration information: ClinicalTrials.gov NCT04492020. Submitted: July 27, 2020; first patient enrolled: August 21, 2020. clinicaltrials.gov/ct2/show/NCT04492020.

Classification of evidence: This study provides Class II evidence that taking ubrogepant 100 mg during a migraine prodrome allows more patients to function normally over the next 24 hours.

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Conflict of interest statement

R.B. Lipton has received research support from the National Institutes of Health, the FDA, and the National Headache Foundation, serves as consultant for, advisory board member of, or has received honoraria or research support from AbbVie/Allergan, Amgen, Biohaven, electroCore, Eli Lilly, GlaxoSmithKline, Lundbeck, Merck, Novartis, Teva, Vector, and Vedanta Research, receives royalties from Wolff's Headache, 8th edition (Oxford University Press, 2009), and Informa, and holds stock/options in Axon, Biohaven, Cooltech, and Manistee. A.M. Harriott has received personal compensation for serving as an officer or member of the Board of Directors for Headache Cooperative of New England, their institution has received research support from electroCore, and has a non-compensated relationship as an author with AbbVie that is relevant to AAN interests or activities. D.W. Dodick reports the following conflicts: Consulting: Amgen, Atria, CapiThera Ltd., Cerecin, Ceruvia Lifesciences LLC, CoolTech, Ctrl M, Allergan, AbbVie, Biohaven, GlaxoSmithKline, Lundbeck, Eli Lilly, Novartis, Impel, Satsuma, Theranica, WL Gore, Genentech, Nocira, Perfood, Praxis, AYYA Biosciences, Revance, and Pfizer. Honoraria: American Academy of Neurology, the Headache Cooperative of the Pacific, the Canadian Headache Society, MF Med Ed Research, Biopharm Communications, CEA Group Holding Company (Clinical Education Alliance LLC), Teva (speaking), Amgen (speaking), Eli Lilly (speaking), Lundbeck (speaking), Pfizer (speaking), Vector Psychometric Group, Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Academy for Continued Healthcare Learning, Majallin LLC, Medlogix Communications, Medica Communications LLC, MJH Lifesciences, Miller Medical Communications, WebMD Health/Medscape, Wolters Kluwer, Oxford University Press, and Cambridge University Press. Non-profit board membership: American Brain Foundation, American Migraine Foundation, ONE Neurology, Precon Health Foundation, International Headache Society Global Patient Advocacy Coalition, Atria Health Collaborative, Arizona Brain Injury Alliance, and the Domestic Violence HOPE Foundation/Panfila. Research support: Department of Defense, National Institutes of Health, the Henry Jackson Foundation, the Sperling Foundation, the American Migraine Foundation, and the Patient Centered Outcomes Research Institute (PCORI). Stock options/shareholder/patents/board of directors: Ctrl M (options), Aural Analytics (options), ExSano (options), Palion (options), Man and Science, Healint (options), Theranica (options), Second Opinion/Mobile Health (options), Epien (options/board), Nocira (options), Matterhorn (shares/board), Ontologics (shares/board), King-Devick Technologies (options/board), Precon Health (options/board), AYYA Biosciences (options), Axon Therapeutics (options/board), Cephalgia Group (options/board), Atria Health (options/employee). Patent 17189376.1-1466:vTitle: Onabotulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis (Nonroyalty bearing). Patent application submitted: Synaquell (Precon Health). J.Y. Ma, J.H. Smith, J. Stokes, P. Gandhi, K. Jariwala-Parikh, G.S. Jensen, and J.M. Trugman are employees of AbbVie and may hold AbbVie stock. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Study Disposition
The safety population included all treated participants who took ≥1 administration of the study drug. The modified intent-to-treat (mITT) population included all randomly assigned participants with at least 1 assessment of headache occurrence within 24 hours after taking the double-blind study drug for at least 1 qualifying prodrome event. Reprinted from Dodick DW, Goadsby PJ, Schwedt TJ, et al. Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA. Lancet. 2023;402(10419):2307-2316. Copyright © 2023, with permission from Elsevier.
Figure 2
Figure 2. Ability to Function Normally After Treatment During the Prodrome
Responders were those with a Functional Disability Scale score of 0 (no disability, able to function normally). Percentages were calculated as the number of responders over the number of participants with nonmissing ability to function normally assessed at each time point after dose. Baseline data were collected before dose. *p < 0.05 vs placebo; ‡p < 0.001 vs placebo. p Values represent nominal p values, without adjustment for multiplicity.
Figure 3
Figure 3. Proportion of Participants With Little or No Activity Limitation Over 24 Hours After Dose After Treatment With Ubrogepant or Placebo During the Prodrome
Responders were those who reported “not at all limited—I could do everything” or “a little limited.” Percentages were calculated as the number of responders over the number of participants with nonmissing activity limitation assessment at each time point after dose. ‡p < 0.001 vs placebo. p Values represent nominal p values, without adjustment for multiplicity.
Figure 4
Figure 4. Satisfaction With Study Medication at 8 and 24 Hours After Dose After Treatment With Ubrogepant or Placebo During the Prodrome
Responders were those who reported that they were “satisfied” or “extremely satisfied.” Percentages were calculated as the number of responders over the number of participants with nonmissing satisfaction with study medication assessment at each time point after dose. ‡p < 0.001 vs placebo. p Values represent nominal p values, without adjustment for multiplicity.
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