Phase Ib, open-label, fixed-sequence, drug-drug interaction, safety, and tolerability study between atogepant and ubrogepant in participants with a history of migraine.

Autor: Blumenfeld AM; Headache Center of Southern California, Carlsbad, California, USA., Boinpally R; Clinical Pharmacology, AbbVie Inc., Madison, New Jersey, USA., De Abreu Ferreira R; Clinical Pharmacology, AbbVie Inc., Madison, New Jersey, USA., Trugman JM; Clinical Pharmacology, AbbVie Inc., Madison, New Jersey, USA., Dabruzzo B; Clinical Pharmacology, AbbVie Inc., Madison, New Jersey, USA., Ailani J; MedStar Georgetown University Hospital, Washington, District of Columbia, USA., Lipton RB; The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.; Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York, USA.; Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
Jazyk: angličtina
Zdroj: Headache [Headache] 2023 Mar; Vol. 63 (3), pp. 322-332. Date of Electronic Publication: 2023 Jan 05.
DOI: 10.1111/head.14433
Abstrakt: Objective: To evaluate potential drug-drug interactions of ubrogepant and atogepant.
Background: Ubrogepant and atogepant, calcitonin gene-related peptide (CGRP) receptor antagonists, are recently approved drugs for acute and preventive treatment of migraine, respectively. For patients with migraine who are prescribed atogepant for the preventive treatment of migraine, health care providers could prescribe ubrogepant for the acute treatment of breakthrough migraine attacks.
Methods: A phase Ib, multi-center, open-label, fixed-sequence study was conducted in participants diagnosed with migraine for at least 1 year. To assess the primary objective of pharmacokinetic interactions in this phase I trial, the highest United States Food and Drug Administration-approved individual dose strengths of atogepant (60 mg once daily) and ubrogepant (100 mg) were utilized, with ubrogepant being administered on a fixed-dose schedule every 3 days, regardless of whether a participant was experiencing a migraine attack. Secondary endpoints included safety and tolerability. Clinical safety measurements were monitored throughout the study.
Results: Of the 31 participants enrolled, 26 completed the study. A single dose of ubrogepant had no statistically significant effect on atogepant pharmacokinetics. Co-administration of ubrogepant with atogepant resulted in a 19% increase (geometric mean ratio 118.80, 90% confidence interval [CI] 108.69-129.84) in the ubrogepant area under the plasma concentration-time curve and a 26% increase (geometric mean ratio 125.63, 90% CI 105.58-149.48) in the ubrogepant maximum plasma concentration. These statistically significant changes in ubrogepant exposure were not clinically meaningful, and no new safety concerns were identified for the combination.
Conclusion: The combination use of atogepant and ubrogepant was safe and well tolerated in adult participants with a history of migraine enrolled in the study. Pharmacokinetic changes during co-administration were not clinically meaningful.
(© 2023 AbbVie Inc and The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)
Databáze: MEDLINE
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