Abstract Details

Title Evaluation of the Pharmacokinetic Interaction and Safety of Coadministered Atogepant and Topiramate

Topic Headache

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 15-004

Objective To evaluate the potential for pharmacokinetic (PK) drug-drug interactions (DDIs) between atogepant and topiramate, as well as to evaluate the safety and tolerability profiles when these 2 medications are coadministered vs administered alone.

Background Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist in development for the preventive treatment of migraine. Topiramate is an approved treatment for adults for the prevention of migraine and is a mild inducer of CYP3A4 activity with a long elimination half-life (approximately 21 hours). The potential for a DDI between atogepant and topiramate when coadministered has yet to be characterized.

Design/Methods Phase 1, single-center, open-label, multiple-dose study. Healthy adults (18–45 y) were randomized to cohort 1 to evaluate the effect of topiramate (mild CYP3A4 inducer) 100mg twice daily on the PK of atogepant (CYP3A4 substrate) 60mg once daily, or cohort 2 to evaluate the effect of atogepant 60mg once daily on the PK of topiramate 100mg twice daily. Blood samples were collected to evaluate the potential for PK DDIs. Safety was monitored throughout the study.

Results A total of 28 and 25 participants were enrolled in cohorts 1 and 2, respectively. For atogepant, overall systemic exposure (AUC0-tau) and maximum plasma concentration (Cmax) were reduced by 25% and 24%, respectively, with topiramate coadministration. Atogepant median Tmax was the same when administered alone or with topiramate (2h). For topiramate, AUC0-tau and Cmax were reduced by 5% and 6%, respectively, with atogepant coadministration. Topiramate median Tmax was delayed by 0.5h when coadministered with atogepant. Administration of atogepant and topiramate, alone and in combination, was safe and well tolerated.

Conclusions Atogepant AUC0-tau and Cmax decreased by 25% and 24% when coadministered with topiramate. Given the wide effective dose range for atogepant, these changes are not expected to be clinically significant and no dose adjustments are needed.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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