Evaluation of the Pharmacokinetic Interactions and Safety of Atogepant Coadministered with Esomeprazole

Abstract

Aim: To investigate potential pharmacokinetic interactions between atogepant and esomeprazole. Methods: Atogepant, esomeprazole, or both were administered to 32 healthy adults in an open-label, nonrandomized, crossover study. Systemic exposure (area under the plasma concentration–time curve [AUC] and peak plasma concentration [C_max]) for atogepant administered in combination versus alone were compared using a linear mixed effects model. Results: Coadministration with esomeprazole delayed atogepant time to C_max by ∼1.5 h and reduced C_max by ∼23% with no statistically significant change in AUC compared with atogepant alone. Administration of atogepant 60 mg alone or in combination with esomeprazole 40 mg was well tolerated in healthy adults. Conclusion: Esomeprazole had no clinically meaningful effect on atogepant pharmacokinetics.

Clinical Trial Registration: unregistered phase I study

Plain language summary

A clinical study was conducted in 32 healthy adults to evaluate the possibility of interactions between atogepant, a new drug for the prevention of migraine, and esomeprazole, a drug used to reduce stomach acid. The participants of the study were given each drug alone and together to understand the effect they had on the body’s ability to absorb, distribute, and excrete each drug alone and together. The results of this study show that there are no clinically important changes in how atogepant is processed by the body when administered with esomeprazole, and they can be safely taken together.

Keywords::

• atogepant
• CGRP receptor antagonist
• drug–drug interaction
• esomeprazole
• migraine prevention
• oral
• pharmacokinetics

Author contributions

Study concept and design: R Boinpally, A Papinska. Acquisition of data: J Rojo and L Borbridge. Analysis and interpretation of data: all authors. Revising the manuscript for intellectual content: all authors. Final approval of the completed manuscript: all authors.

Acknowledgments

The authors thank AbbVie employees, R De Abreu Ferreira, K Li and S Varughese, for their helpful discussions and feedback on the manuscript.

Financial & competing interests disclosure

This study was funded by Allergan (prior to its acquisition by AbbVie). AbbVie contributed to the research and interpretation of the data and the writing, review, and approval of the manuscript. R Boinpally, L Borbridge and V Wangsadipura are employees of AbbVie and may hold AbbVie stock or stock options. J Rojo, M Butler and A Papinska are former AbbVie employees and may hold stock or stock options. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing support was provided by S Koeniger, an employee with AbbVie.

Ethical conduct of research

The study reported herein was conducted in accordance with the International Council for Harmonisation (ICH) guidelines, applicable regulations, and guidelines governing clinical study conduct and the ethical principles that have their origin in the Declaration of Helsinki. Approval was granted by institutional review boards and independent ethics committees at participating institutions. All participants provided written consent prior to participation or study-related procedures. All individual participants signed informed consent regarding publishing their data.

Data sharing statement

The authors certify that this manuscript reports original clinical trial data. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: www.abbvieclinicaltrials.com/hcp/data-sharing/.html

Additional information

Funding

This study was funded by Allergan (prior to its acquisition by AbbVie). AbbVie contributed to the research and interpretation of the data and the writing, review, and approval of the manuscript. R Boinpally, L Borbridge and V Wangsadipura are employees of AbbVie and may hold AbbVie stock or stock options. J Rojo, M Butler and A Papinska are former AbbVie employees and may hold stock or stock options. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing support was provided by S Koeniger, an employee with AbbVie.