Single-Dose Pharmacokinetics and Safety of Ubrogepant in Adults With Hepatic Impairment: Results From an Open-Label, Phase 1 Trial.

Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the treatment of acute migraine headaches. Ubrogepant demonstrated efficacy and safety in 2 pivotal phase 3 studies (N = 2240) that led to its approval. Here, we report the pharmacokinetics and safety results from a phase 1 study in which participants with severe (n = 4), moderate (n = 8), or mild (n = 8) hepatic impairment and matched participants with normal hepatic function (n = 8) were administered a single dose of 100 mg of ubrogepant. Twenty-eight participants aged 36 to 70 years were enrolled and completed the study. In participants with mild, moderate, or severe hepatic impairment, ubrogepant systemic exposure (area under the plasma concentration-time curve) increased by 7%, 52%, and 115%, respectively, compared with participants with normal hepatic function (≈1600 ng • h/mL). Peak exposure increased by 1%, 18%, and 26%, respectively, in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function (≈400 ng/mL). Plasma protein binding did not change significantly across groups. No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Dose adjustment (50 mg) is recommended for patients with severe hepatic impairment. Single doses of ubrogepant 100 mg were safe, and all the enrolled participants, regardless of hepatic function, completed the study.