Abstract Details

Title Cerebrospinal Fluid and Plasma Concentrations of Ubrogepant in Participants with a History of Migraine

Topic Headache

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-008

Objective To determine the cerebrospinal fluid (CSF) to plasma concentration ratio of ubrogepant in participants with a history of migraine.

Background Ubrogepant is an orally active CGRP receptor antagonist approved for the acute treatment of migraine in adults.

Design/Methods In a Phase 1b multi-center, open-label, study 8 male and female participants who had been diagnosed with migraine for at least 1 year were administered a single 100 mg dose of ubrogepant. Plasma and CSF concentrations of ubrogepant were determined using LC-MS/MS methods. Ubrogepant CSF/plasma concentration ratio at each time point for each participant was calculated. Descriptive statistics for the ubrogepant CSF/plasma ratio were calculated for each time point. The safety and tolerability profiles of ubrogepant were evaluated by clinical assessment of adverse events, physical examinations, 12-lead ECGs, laboratory tests (hematology, serum chemistry, and urinalysis), and vital sign measurements.

Results Mean(SD) plasma and CSF ubrogepant concentrations at 2 hours were 354(163) and 1.08(0.8) ng/mL, respectively and at 4 hours were 218(84) and 2.26(1.94) ng/mL, respectively. The mean ubrogepant CSF/plasma concentration ratio was 0.36% at 2 hours post-dose and 0.94% at 4 hours post-dose. There were no serious adverse events, deaths, significant changes in clinical labs, vital signs, or ECGs.

Conclusions Ubrogepant concentrations in the CSF are approximately 1% of plasma concentrations at 4 hours post-dose. Based on the results of pharmacodynamic assessments of the inhibition of capsaicin-induced increases in forearm dermal blood flow suggesting ubrogepant EC₅₀ value of approximately 1.41 ng/mL, the CSF concentrations observed at 4 hours post-dose suggest that ubrogepant could act both centrally and peripherally to relieve migraine symptoms.

Authors/Disclosures
Ramesh R. Boinpally (Abbvie) PRESENTER	Dr. Boinpally has received personal compensation for serving as an employee of Abbvie. Dr. Boinpally has stock in Abbvie. Dr. Boinpally has received intellectual property interests from a discovery or technology relating to health care.
Joel M. Trugman, MD, FAAN	Dr. Trugman has received personal compensation for serving as an employee of AbbVie. Dr. Trugman has stock in AbbVie.

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