Abstract Details

Title Single and Multiple Doses of Ubrogepant Are Not Associated With a Clinically Significant Elevation of Alanine Aminotransferase in Healthy Adult Males

Topic Headache

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 13-014

Objective To evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple oral ubrogepant doses in healthy male volunteers.

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

Design/Methods A two-part, randomized, double-blind, placebo-controlled study was conducted. Healthy male subjects (aged 18-50 years) were randomized to (1) a single dose of ubrogepant (100-400 mg) or placebo, or (2) multiple doses of ubrogepant (40-400 mg) or placebo once daily for 10 days. A spray-dried oral compressed tablet (OCT) formulation of ubrogepant was used. Endpoints included safety/tolerability and PK; hepatic safety results were assessed using geometric mean percentage (GM%) changes from baseline in alanine aminotransferase (ALT).

Results Forty subjects were enrolled and completed the study (age range: 21-51). Single-dose spray-dried OCT ubrogepant was rapidly absorbed, with a T_max of 2 to 3 hours and terminal half-life (t_½) of 3.4 to 4.3 hours. With multiple doses, OCT ubrogepant had a median T_max of 1.8 to 3.5 hours and t_½ of 6.7 to 11.2 hours; steady state was reached within 2 days. No serious adverse events were reported. The most common adverse events were nasopharyngitis, nausea, diarrhea, and headache. With single-dose ubrogepant, GM% changes from baseline in ALT at 24 hours were -13.1% to 10.0% versus -1.6% with placebo. With multiple-dose ubrogepant, the changes were -19.4% to 7.5% across doses at 24 hours (n=24; 40-400 mg) versus -10.3% with placebo. No subjects had ALT elevations >3× the upper limit of normal.

Conclusions The PK of ubrogepant in healthy male adults makes it suitable for use as an acute treatment of migraine. Single and multiple doses of ubrogepant up to 400 mg were well tolerated, and no evidence of drug-related elevations in ALT was observed with ubrogepant administered as single or multiple doses over 10 days.

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
	No disclosure on file
Abhijeet Jakate, PhD (Allergan Plc)	No disclosure on file
	No disclosure on file

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