TY - JOUR
T1 - Phase Ib, open-label, fixed-sequence, drug–drug interaction, safety, and tolerability study between atogepant and ubrogepant in participants with a history of migraine
AU - Blumenfeld, Andrew M.
AU - Boinpally, Ramesh
AU - De Abreu Ferreira, Rosa
AU - Trugman, Joel M.
AU - Dabruzzo, Brett
AU - Ailani, Jessica
AU - Lipton, Richard B.
N1 - Publisher Copyright:
© 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.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - CGRP receptor antagonists
KW - atogepant
KW - drug–drug interaction
KW - migraine
KW - ubrogepant
UR - http://www.scopus.com/inward/record.url?scp=85146082300&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85146082300&partnerID=8YFLogxK
U2 - 10.1111/head.14433
DO - 10.1111/head.14433
M3 - Article
C2 - 36602199
AN - SCOPUS:85146082300
SN - 0017-8748
VL - 63
SP - 322
EP - 332
JO - Headache
JF - Headache
IS - 3
ER -