Abstract Details

Title Safety and Tolerability of Ubrogepant Following Intermittent, High Frequency Dosing

Topic Headache

Presentation(s) S17 - Headache: Clinical Trials I (2:28 PM-2:39 PM)

Poster/Presentation
Number 009

Background Ubrogepant is a novel, oral CGRP receptor antagonist in development for the acute treatment of migraine. It has structural modifications to increase potency and minimize risk of hepatotoxicity compared to previous gepants.

Objective To evaluate the safety and tolerability of ubrogepant, focusing on hepatic safety, when administered intermittently with high frequency dosing, to healthy participants.

Design/Methods Phase 1, multicenter, double-blind, parallel-group trial. Participants randomized 1:1 to placebo or ubrogepant 100-mg. Those on ubrogepant took 100-mg on 2 consecutive days followed by 2 consecutive days of placebo, alternating for 8 weeks. Adults (age 18-50 years) with no significant medical history and normal hepatic function were included. Primary outcome measures were safety and tolerability.

Results A total of 518 participants were randomized; 516 in the safety population (n=260 placebo; n=256 ubrogepant). Participants’ mean age was 32 years, 55% female, 68% White, 25% Black/African American, average BMI=25; population differed from the typical migraine population. Treatment-emergent adverse events (AEs): 45% participants on placebo, 44% ubrogepant; most common was headache (10% placebo; 11% ubrogepant). Treatment-related AEs: 19% placebo, 22% ubrogepant. Serious AEs: 0.4% placebo, 0.8% ubrogepant; none considered treatment-related. 7 cases of ALT/AST ≥3x ULN (five placebo, two ubrogepant) were reported and adjudicated by a panel of independent liver experts blinded to treatment. All but 3 cases were judged Unlikely Related based on plausible alternative etiologies/confounding factors. Two cases (one placebo, one ubrogepant) were judged Possibly Related. One case (ubrogepant) was judged Probably Related. ALT increases ≥3x ULN were not confirmed with repeat testing and resolved with continued dosing. All cases were asymptomatic and no cases with concurrent bilirubin elevation.

Conclusions Ubrogepant was well-tolerated following intermittent, high frequency dosing in healthy participants with no identified safety concerns. Treatment with ubrogepant was not associated with persistent increased ALT/AST compared to placebo, supporting liver safety.

Authors/Disclosures
Joel M. Trugman, MD, FAAN PRESENTER	Dr. Trugman has received personal compensation for serving as an employee of AbbVie. Dr. Trugman has stock in AbbVie.
Peter Goadsby, MD, PhD, FRS (University of California, Los Angeles)	Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli-Lilly. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aurene. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shiratronics. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CoolTech LLC. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Linpharma. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PureTech Health LLC. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vial. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon Biopharma. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Massachusetts Medical Society. The institution of Dr. Goadsby has received research support from NIHR. The institution of Dr. Goadsby has received research support from Kallyope. Dr. Goadsby has received publishing royalties from a publication relating to health care. Dr. Goadsby has received publishing royalties from a publication relating to health care. Dr. Goadsby has a non-compensated relationship as a Trustee with Migraine Trust that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Trustee with Organisation for Understanding Cluster Headache (UK) that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Executive roles with American Headache Society that is relevant to AAN interests or activities.
Stewart J. Tepper, MD (The New England Institute for Neurology and Headache)	Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aeon. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aruene. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atheneum. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Becker Pharmaceutical Consulting. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clearview Healhcare Partners. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CoolTech. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CRG. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Decision Resources. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Defined Health. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for DRG. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ExpertConnect. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FCB Health. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fenix. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Health Advances. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Health Science Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HMP Communications. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Impel. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for InteractiveForums. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Keyquest. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Krog and Partners. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for M3 Global Research. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Magnolia Innovation. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MJH Holdings. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for P Value Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pain Insights Inc. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Palion Medical. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pulmatrix. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Putnam Associates. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SAI MedPartners. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Slingshot Insights. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spherix Global Insights. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Strategy Inc. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for System Analytic. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Taylor and Francis. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Trinity Partners. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UnityHA. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for XOC. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Click Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Miravo. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurofront Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rehaler. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Synapse Medical Communications. Dr. Tepper has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Pfizer. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alphasights. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Perfood. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for M3 Global Research. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Scilex. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Synapse Medical Communication. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tegus. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Catch Therapeutics. Dr. Tepper has received personal compensation in the range of $0-$499 for serving as a Consultant for DocDelta. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Dr Reddy's. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FCB Health. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilmartin Capital. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Initiator Pharma. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Magellan Health. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Nocira. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Slingshot Insights. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Third Bridge. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tonix. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vial . Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for DocDelta. The institution of Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bausch Health. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Dr Reddy's. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ClickTherapeutics. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CoolTech. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Miravo Healthcare. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pulmatrix. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Satsuma. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AbbVie. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lundbeck. Dr. Tepper has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Pfizer. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Scilex. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Tonix. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Dr Reddy's. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eli Lilly. The institution of Dr. Tepper has received research support from Abbvie. The institution of Dr. Tepper has received research support from Aeon. The institution of Dr. Tepper has received research support from Amgen. The institution of Dr. Tepper has received research support from Annovis. The institution of Dr. Tepper has received research support from Axsome. The institution of Dr. Tepper has received research support from Cassava. The institution of Dr. Tepper has received research support from Cognition. The institution of Dr. Tepper has received research support from Eli Lilly. The institution of Dr. Tepper has received research support from Inibikase. The institution of Dr. Tepper has received research support from Ipsen. The institution of Dr. Tepper has received research support from Lundbeck. The institution of Dr. Tepper has received research support from Merz. The institution of Dr. Tepper has received research support from Pfizer. The institution of Dr. Tepper has received research support from PrecisionMed. The institution of Dr. Tepper has received research support from Revance. The institution of Dr. Tepper has received research support from Suven. The institution of Dr. Tepper has received research support from UCB. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Diamond Headache Clinic. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with Medical Learning Institute Peerview. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with Medical ��ɫ�� Speakers Network. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Miller Medical Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with Physicians' ��ɫ�� Resource. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with WebMD/Medscape. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with American Headache Society. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Vindico Medical ��ɫ��. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with HMP Global. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CMe speaker with Medical Learning Institute Peerview. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Speaker with Consortium for Research ��ɫ�� Social Awareness and Training In Neurosciences.
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Michelle Finnegan	Michelle Finnegan has received personal compensation for serving as an employee of AbbVie.
	No disclosure on file
Abhijeet Jakate, PhD (Allergan Plc)	No disclosure on file

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