Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis

Introduction Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids. The pharmacokinetics of elagolix have been well-characterized in phase I studies; however, elagolix population pharmacokinetics have not been previously reported. Therefore, a robust model was developed to describe elagolix population pharmacokinetics and to evaluate factors affecting elagolix pharmacokinetic parameters.

The data from nine clinical studies (a total of 1624 women) were included in the analysis: five phase I studies in healthy, premenopausal women and four phase III studies in premenopausal women with endometriosis.

Elagolix population pharmacokinetics were best described by a two-compartment model with a lag time in absorption. Of the 15 covariates tested for effect on elagolix apparent clearance (CL/F) and/or volume of distribution only one covariate, organic anion transporting polypeptide (OATP) 1B1 genotype status, had a statistically significant, but not clinically meaningful, effect on elagolix CL/F.

Elagolix pharmacokinetics were not affected by patient demographics and were similar between healthy women and women with endometriosis. Clinical Trial Registration Numbers NCT01403038, NCT01620528, NCT01760954, NCT01931670, NCT02143713. Similar content being viewed by others

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We thank AbbVie employee Sonja Kemmis Causemaker for medical writing support for this manuscript. We also thank AbbVie employee Xiaohua Du for dataset programming efforts. Author information Authors and Affiliations Contributions All authors contributed to the study design and analysis and interpretation of the data. All authors participated in the drafting and revising of the manuscript. Corresponding author Ethics declarations Funding AbbVie provided financial support for the study and participated in the design, study conduct, analysis, and interpretation of data as well as the writing, review, and approval of the manuscript. Conflict of interest Insa Winzenborg, Ahmed Nader, Akshanth R. Polepally, Mohan Liu, Jacob Degner, Cheri E. Klein, Nael M. Mostafa, Peter Noertersheuser, and Juki Ng are employees of AbbVie, Inc. and may hold stock or stock options. Electronic supplementary material Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Winzenborg, I., Nader, A., Polepally, A.R. et al. Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis. Clin Pharmacokinet 57, 1295–1306 (2018). https://doi.org/10.1007/s40262-018-0629-6 Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s40262-018-0629-6