Acute treatment of migraine with ubrogepant, an oral calcitonin gene-related peptide antagonist, was superior to placebo regarding the rate of pain freedom in a phase 3 clinical trial. The results were recently published in JAMA.
The study, a phase 3, double-blind clinical trial (ACHIEVE II: NCT02867709), included adult patients with migraine with or without aura (mean age, 41.5 years; 90% female) who reported 2 to 8 migraine attacks per month. Patients were randomly assigned to ubrogepant 50 mg (n=488), ubrogepant 25 mg (n=478), or placebo (n=499) for migraine attacks of moderate or severe pain intensity. Pain freedom and the absence of most bothersome symptoms at 2 hours following treatment comprised the coprimary efficacy outcome.
Compared with placebo, a significantly higher proportion of participants receiving the study drug reported pain freedom at 2 hours following treatment. In the ubrogepant 50-mg group 21.8% of patients reported pain relief vs 14% in the placebo group (absolute difference, 7.5%; 95% CI, 2.6%-12.5%; P =.01). A similar response was seen in the ubrogepant 25-mg group, with 20.7% of patients reporting pain relief compared with 14.3% in the placebo group (absolute difference, 6.4%; 95% CI, 1.5%-11.5%; P =.03).
Approximately 38.9% of patients in the ubrogepant 50-mg group reported absence of the most bothersome symptom at 2 hours compared with 27.4% of patients who received placebo (absolute difference, 11.5%; 95% CI, 5.4%-17.5%; P = .01). A significantly greater proportion of patients who received ubrogepant 25 mg also reported absence of the most bothersome symptoms at 2 hours vs placebo (34.1% vs 27.4%, respectively; absolute difference, 6.7%; 95% CI, 0.6%-12.7%; P =.07).
Common adverse events associated with any ubrogepant dose within 48 hours of administration included nausea (50 mg: 2.0%; 25 mg: 2.5%; placebo: 2.0%) and dizziness (50 mg: 1.4%; 25 mg: 2.1%; placebo: 1.6%).
Limitations of the study included the treatment of only moderate or severe migraine and the assessment of safety and tolerability data after only a single migraine attack.
The researchers noted that additional studies may be necessary to evaluate the efficacy “of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations.”
Disclosure: This clinical trial was supported by Allergan plc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Lipton RB, Dodick DW, Ailani J, et al. Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial. JAMA. 2019;322(19):1887-1898