BACKGROUND: Ubrogepant is an oral, small-molecule calcitonin gene-related 
peptide receptor antagonist for acute migraine treatment.
METHODS: We conducted a randomized trial to evaluate the efficacy, safety, and 
side-effect profile of ubrogepant. We assigned adults with migraine, with or 
without aura, in a 1:1:1 ratio to receive an initial dose of placebo, ubrogepant 
at a dose of 50 mg, or ubrogepant at a dose of 100 mg for treatment of a single 
migraine attack, with the option to take a second dose. The coprimary efficacy 
end points were freedom from pain at 2 hours after the initial dose and absence 
of the most bothersome migraine-associated symptom at 2 hours. Secondary end 
points included pain relief (at 2 hours), sustained pain relief (from 2 to 24 
hours), sustained freedom from pain (from 2 to 24 hours), and absence of 
symptoms associated with migraine (photophobia, phonophobia, and nausea) at 2 
hours.
RESULTS: A total of 1672 participants were enrolled; 559 were assigned to 
receive placebo, 556 to receive 50 mg of ubrogepant, and 557 to receive 100 mg 
of ubrogepant. The percentage of participants who had freedom from pain at 2 
hours was 11.8% in the placebo group, 19.2% in the 50-mg ubrogepant group 
(P = 0.002, adjusted for multiplicity, for the comparison with placebo), and 
21.2% in the 100-mg ubrogepant group (P<0.001). The percentage of participants 
who had freedom from the most bothersome symptom at 2 hours was 27.8% in the 
placebo group, 38.6% in the 50-mg ubrogepant group (P = 0.002), and 37.7% in the 
100-mg ubrogepant group (P = 0.002). Adverse events within 48 hours after the 
initial or optional second dose were reported in 12.8% of participants in the 
placebo group, in 9.4% in the 50-mg ubrogepant group, and in 16.3% in the 100-mg 
ubrogepant group. The most common adverse events were nausea, somnolence, and 
dry mouth (reported in 0.4 to 4.1%); these events were more frequent in the 
100-mg ubrogepant group (reported in 2.1 to 4.1%). Serious adverse events 
reported within 30 days in the ubrogepant groups included appendicitis, 
spontaneous abortion, pericardial effusion, and seizure; none of the events 
occurred within 48 hours after the dose.
CONCLUSIONS: A higher percentage of participants who received ubrogepant than of 
those who received placebo had freedom from pain and absence of the most 
bothersome symptom at 2 hours after the dose. The most commonly reported adverse 
events were nausea, somnolence, and dry mouth. Further trials are needed to 
determine the durability and safety of ubrogepant for acute migraine treatment 
and to compare it with other drugs for migraine. (Funded by Allergan; 
ClinicalTrials.gov number, NCT02828020.).