Objective:

To evaluate milk and plasma pharmacokinetics (PK) and relative infant dose (RID) of atogepant following single-dose administration to healthy lactating women.

Background:

Atogepant is an orally active CGRP receptor antagonist approved for the prophylaxis of migraine in adults.

Design/Methods:

In a Phase 1, open-label study, 12 healthy lactating women, one to six months post-partum, were administered 60mg single dose atogepant. Milk and plasma samples were collected for 24 hours, atogepant concentrations determined using LC-MS/MS, and PK parameters calculated. The safety and tolerability of atogepant were evaluated by assessing adverse events, physical examinations, 12-lead ECGs, laboratory tests (hematology, serum chemistry, and urinalysis), and vital sign measurements.

Results:

Atogepant milk concentrations were much lower than plasma concentrations and were below the LLOQ beyond 16 hours in the majority participants. The average milk:plasma concentration ratio was 0.076, and the RID was 0.188%. Mean cumulative amount of atogepant excreted in breast milk after a 60 mg dose was 0.015 mg, representing the actual infant dose should the infant drink all the milk produced. There were 2 mild adverse events, one abdominal pain upper and one dyspepsia, and no serious adverse events, clinically relevant changes in clinical labs, vital signs, or ECGs.

Conclusions:

Atogepant average milk:plasma concentration ratio was 0.076 following a 60mg dose in lactating women. Based on lack of atogepant accumulation upon daily dosing, the low cumulative amount of atogepant excreted in breast milk and the low RID of 0.188%, atogepant may be considered, for the preventive treatment of migraine in lactating women.