Pharmacokinetics and Safety of Coadministered Atogepant and Topiramate in Healthy Participants: A Phase 1, Open-Label, Drug-Drug Interaction Study

Abstract

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, and topiramate, a commonly used oral antiepileptic, are approved as preventive migraine treatments. Given the distinct mechanisms of action of these treatments, it is possible that they may be coprescribed for migraine. This open-label, single-center, 2-cohort, phase 1 trial evaluated the potential pharmacokinetic (PK) 2-way drug-drug interactions (DDIs), safety, and tolerability of atogepant and topiramate in healthy adults. Participants received atogepant 60 mg once daily and topiramate 100 mg twice daily. Cohort 1 (N = 28) evaluated the effect of topiramate on the PK of atogepant; cohort 2 (N = 25) evaluated the effect of atogepant on the PK of topiramate. Potential DDIs were assessed using geometric mean ratios and 90% confidence intervals calculated for maximum plasma drug concentration at steady state (C_max,ss ) and area under the plasma concentration-time curve during the dosing interval at steady state (AUC_0-tau,ss ). Additional PK parameters were assessed. Atogepant AUC_0-tau,ss and C_max,ss decreased by 25% and 24%, respectively, with topiramate coadministration. Topiramate AUC_0-tau,ss and C_max,ss decreased by 5% and 6%, respectively, with atogepant coadministration. The 25% reduction in atogepant exposure when coadministered with topiramate is not considered to be clinically relevant and would not require dose adjustments.

Keywords: CGRP receptor antagonist; atogepant; drug-drug interactions; migraine; topiramate.