Ubrogepant for the Acute Treatment of Migraine: Pooled Safety and Tolerability from ACHIEVE I and ACHIEVE II Phase 3 Studies

Objective: To evaluate the safety and tolerability of ubrogepant from the pooled ACHIEVE I and ACHIEVE II trials. Background: Ubrogepant is an oral calcitonin gene–related peptide (CGRP) receptor antagonist in development for the acute treatment of migraine. Safety and tolerability are important factors when considering potential acute treatments for migraine. Design/Methods: ACHIEVE I and II (NCT02828020; NCT02867709) were multicenter, double-blind, single-attack, phase 3 trials conducted in adults with migraine randomized 1:1:1 to placebo or ubrogepant (50 mg or 100 mg, ACHIEVE I; 25 mg or 50 mg, ACHIEVE II). Adverse events (AEs) were evaluated within 48 hours of dosing and within 30 days of any dose. Data from the placebo and ubrogepant 50 mg treatment groups were pooled. Results: The pooled safety population (N=2901; placebo [n=984]; ubrogepant 50 mg [n=954]) had an average age of 41 years and the majority were female (89% placebo; 90% ubrogepant 50 mg) and white (82% both groups). Within 48 hours of dosing, 113/984 (11.5%) placebo and 107/954 (11.2%) ubrogepant 50 mg participants reported ≥1 treatment-emergent AE (TEAE), the most common being nausea (placebo, 1.8%; ubrogepant 50 mg, 1.9%). Treatment-related AEs were reported in 71/984 (7.2%) placebo and 69/954 (7.2%) ubrogepant 50 mg participants. No serious AEs (SAEs) were reported. Within 30 days of any dose, 225/984 (22.9%) placebo and 259/954 (27.1%) ubrogepant 50 mg participants reported ≥1 TEAE; the most common was nausea (2.2% both groups). Treatment-related AEs were reported in 88/984 (8.9%) placebo and 90/954 (9.4%) ubrogepant 50 mg participants. Three (0.3%) SAEs in ubrogepant 50 mg participants (pericardial effusion, appendicitis, spontaneous abortion) were not treatment-related. Conclusions: Overall, ubrogepant 50 mg was well tolerated, with no new safety concerns identified from the larger, pooled ACHIEVE I and II trial data. Disclosure: Dr. Hutchinson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder, Allergan, Amgen, Avanir, Biohaven, electroCore, Lilly, Novartis, Promius, Supernus, Teva, and Theranica.David W. Dodick, MD, reports the following conflicts: Personal fees: AEON, Alder BioPharmaceuticals, Allergan, Amgen, Amzak Health, Association of Translational Medicine, Autonomic Technologies, Axsome, Biohaven, Charleston Laboratories, Clexio, Daniel Edelman Inc., Dr Reddy’s Laboratories/Promius, electroCore LLC, Eli Lilly, eNeura, Equinox, Foresite Capital, Impel, Ipsen, Neurolief, Nocira, Novartis, Oppenheimer, Pieris, PSL Group Services, Revance, Salvia, Satsuma, Sun Pharma (India), Supernus, Teva, Theranica, University Health Network, Upjohn (Division of Pfizer), Vedanta, WL Gore, XoC, Zosano, and ZP Opco; Speaking fees: Amgen, Eli Lilly, Lundbeck, and Novartis Canada; CME fees or royalty payments: Academy for Continued Healthcare Learning, Cambridge University Press, Catamount, Chameleon, Global Access Meetings, Global Life Sciences, Global Scientific Communications, Haymarket, HealthLogix, Medicom Worldwide, MedLogix Communications, Mednet, Miller Medical, Oxford University Press, PeerView, Universal Meeting Management, UpToDate (Elsevier), WebMD Health/Medscape, and Wolters Kluwer Health; Consulting without fee: Aural Analytics, Epien, Healint, Second Opinion/Mobile Health; Professional society fees or reimbursement for travel: American Academy of Neurology, American Brain Foundation, American Headache Society, American Migraine Foundation, Canadian Headache Society, and International Headache Society. Dr. Dodick has received compensation for serving on the Board of Directors of Epien, King-Devick Technologies, Matterhorn, Ontologics, and Precon Health. Dr. Dodick has received research support from American Migraine Foundation, Henry Jackson Foundation, PCORI, and US Department of Defense.Dr. Treppendahl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Christina Treppendahl, FNP-BC, AQH, MHD, served on advisory boards, participated in speaker bureaus or conducted clinical research with Amgen, Electrocore, Ely Lilly, Impax Labs, National Headache Foundation, Pernix, Promius Pharma, Supernus Pharmaceutica. Dr. Treppendahl has received research support from Christina Treppendahl, FNP-BC, AQH, MHD, served on advisory boards, participated in speaker bureaus or conducted clinical research with Amgen, Electrocore, Ely Lilly, Impax Labs, National Headache Foundation, Pernix, Promius Pharma, Supernus Pharmaceutica. Dr. Bennett has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Nate Bennett, MD, has completed clinical research for Avanir, Allergan, Amgen, electroCore, Impax, Lilly, and Teva, has consulted or acted on an advisory board for Allergan, Amgen, Lilly, Pernix, Promius, and Supernus, and has been a speaker for Avanir, A. Dr. Bennett has received research support from Nate Bennett, MD, has completed clinical research for Avanir, Allergan, Amgen, electroCore, Impax, Lilly, and Teva, has consulted or acted on an advisory board for Allergan, Amgen, Lilly, Pernix, Promius, and Supernus, and has been a speaker for Avanir, A. Dr. Yu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sung Yun Yu, BA, is a full-time employee and stockholder of Allergan plc.. Dr. Yu holds stock and/or stock options in Sung Yun Yu, BA, is a full-time employee and stockholder of Allergan plc. which sponsored research in which Dr. Yu was involved as an investigator. Dr. Yu holds stock and/or stock options in Sung Yun Yu, BA, is a full-time employee and stockholder of Allergan plc.. Dr. Yu has received research support from Sung Yun Yu, BA, is a full-time employee and stockholder of Allergan plc.. Dr. Guo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc. Dr. Guo holds stock and/or stock options in Allergan plc, which sponsored research in which Dr. Guo was involved as an investigator. Dr. Guo holds stock and/or stock options in Allergan plc. Dr. Guo has received research support from Allergan plc.Dr. Trugman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Joel M. Trugman, MD, is a full-time employee and stockholder of Allergan plc.. Dr. Trugman holds stock and/or stock options in Joel M. Trugman, MD, is a full-time employee and stockholder of Allergan plc. which sponsored research in which Dr. Trugman was involved as an investigator. Dr. Trugman holds stock and/or stock options in Joel M. Trugman, MD, is a full-time employee and stockholder of Allergan plc.. Dr. Trugman has received research support from Joel M. Trugman, MD, is a full-time employee and stockholder of Allergan plc..