Abstract Details

Title Multiple, Once-Daily, Oral Doses of 150 mg Ubrogepant Administered for 28 Days Are Generally Well Tolerated, With No Clinically Significant Elevation of Alanine Aminotransferase in Healthy Adult Males

Topic Headache

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 13-024

Objective To evaluate the hepatic safety of multiple oral 150 mg ubrogepant doses in healthy male volunteers.

Background Ubrogepant is a novel, oral antagonist of the calcitonin gene–related peptide receptor in development for the acute treatment of migraine attacks.

Design/Methods A single-center, randomized, double-blind, placebo-controlled study was conducted. Healthy male subjects 18 to 50 years of age were randomized 2:1 to ubrogepant 150 mg or matching placebo administered orally once daily for 28 days. An oral compressed tablet (OCT) formulation of ubrogepant was used. Endpoints included safety and tolerability and pharmacokinetics. Natural logarithm–transformed fold changes from baseline values for alanine aminotransferase (ALT) were analyzed using a linear mixed-effects model. Least squares means and confidence intervals (CIs) were calculated. The posterior probability that the true mean fold treatment difference in ALT exceeded 1.5 was calculated at the time point with the largest difference.

Results 32 subjects were enrolled and completed the study (22 ubrogepant; 10 placebo; median age: 38.5 years; range: 25-49). OCT ubrogepant was rapidly absorbed: median time to maximum concentration was 2 to 3 hours and mean terminal half-life was 9.9 hours. Daily ubrogepant 150 mg was associated with no serious adverse events and there were no discontinuations due to adverse events. At Day 28, the geometric mean fold change in ALT from baseline with ubrogepant was 0.96 (90% CI: 0.87-1.06) versus 1.07 (90% CI: 0.93-1.24) with placebo, a 0.90-fold treatment difference between ubrogepant and placebo (90% CI: 0.75-1.07). No subjects had ALT elevations >3× the upper limit of normal.

Conclusions No evidence of clinically relevant drug-related elevations in ALT was observed in healthy males who received 28 days of once-daily 150 mg oral ubrogepant.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Abhijeet Jakate, PhD (Allergan Plc)	No disclosure on file
	No disclosure on file

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