Treatment with the orally administered, small-molecule calcitonin gene-related peptide receptor antagonist ubrogepant in patients with acute migraine has been associated with freedom from pain and the absence of the patient-determined most troublesome symptom compared with placebo 2 hours after dosing. A randomized double-blind placebo-controlled parallel-group trial (Efficacy, Safety, and Tolerability Study of Oral Ubrogepant in the Acute Treatment of Migraine [ACHIEVE I]; ClinicalTrials.gov identifier: NCT02828020) on the subject was conducted at 89 centers in the United States between July 22, 2016 and December 14, 2017. Study results were published in The New England Journal of Medicine.
The investigators sought to assess the efficacy, safety, and side-effect profile of ubrogepant vs placebo in patients with acute migraine. A total of 1672 adult patients with migraine with or without aura were assigned in a 1:1:1 ratio to receive 1 of 3 treatments: (1) an initial dose of placebo (n=559); (2) ubrogepant 50 mg (n=556); or (3) ubrogepant 100 mg (n=557) with the option to receive a second dose. Following treatment discontinuation for a variety of reasons, a total of 485 patients in the placebo group, 466 in the ubrogepant 50-mg group, and 485 in the ubrogepant 100-mg group were included in the study population.
The co-primary efficacy end points included freedom from pain 2 hours after receiving the initial dose and absence of the most bothersome patient-determined migraine-related symptom at 2 hours. The secondary study end points were pain relief at 2 hours, sustained pain relief from 2 to 24 hours, and absence of such migraine-linked symptoms as photophobia, phonophobia, and nausea at 2 hours.
Study results showed that the percentage of patients with freedom from pain 2 hours after the initial dose was 11.8% in the placebo arm, 19.2% in the ubrogepant 50-mg arm (P =.002, adjusted for multiplicity for comparison with placebo), and 21.2% in the ubrogepant 100-mg arm (P <.001). Absence of the most troublesome patient-reported migraine-related symptoms was reported by 27.8% of patients in the placebo group, 38.6% in the ubrogepant 50-mg group (P .002), and 37.7% in the ubrogepant 100-mg group (P =.002).
Adverse events within 48 hours following the initial or the optional second dose were reported in 12.8% of patients in the placebo arm, 9.4% in the ubrogepant 50-mg arm, and 9.4% in the ubrogepant 100-mg arm. The most frequent adverse events included nausea, somnolence, and dry mouth. The occurrence of these adverse events was more common in the ubrogepant 100-mg group.
The investigators concluded that additional studies are warranted to determine the durability and safety of ubrogepant for the treatment of acute migraine and to compare the agent with other medications used to treat migraine.
Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the treatment of migraine. N Engl J Med. 2019;81(23):2230-2241.