BACKGROUND: Ubrogepant is a novel, oral calcitonin gene-related peptide (CGRP) 
receptor antagonist in development for the acute treatment of migraine. This 
trial evaluated the safety and tolerability of ubrogepant, focusing on hepatic 
safety, when administered intermittently with high-frequency dosing to healthy 
participants.
METHODS: In this phase 1, multicenter, double-blind, parallel-group trial, 
healthy adults (age 18-50 years) were randomized 1:1 to placebo or ubrogepant. 
Ubrogepant was dosed at 100 mg (2 × 50 mg tablets) on 2 consecutive days 
followed by 2 consecutive days of placebo, alternating for 8 weeks. Primary 
outcome measures were safety and tolerability.
RESULTS: Of participants randomized (n = 518), 516 were included in the safety 
population (n = 260 placebo; n = 256 ubrogepant). Treatment-emergent adverse 
events were reported in 45% of placebo and 44% of ubrogepant participants. The 
most common was headache (10% placebo; 11% ubrogepant). Overall, seven cases of 
alanine aminotransferase and/or aspartate aminotransferase levels ≥ 3 × the 
upper limit of normal (five placebo, two ubrogepant) were reported and 
adjudicated by a panel of independent liver experts blinded to treatment. Four 
cases were judged unlikely related to treatment. Two cases (one placebo, one 
ubrogepant) were judged possibly related, and one (ubrogepant) probably related. 
Alanine aminotransferase increases to ≥ 3 × the upper limit of normal in the two 
ubrogepant cases (possibly or probably related) were transient and resolved with 
continued dosing; both cases were asymptomatic, with no concurrent bilirubin 
elevation.
CONCLUSION: Ubrogepant was well tolerated following intermittent, high-frequency 
dosing in healthy participants, with no clinically relevant signal of 
hepatotoxicity.
TRIAL REGISTRATION: NA.