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Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis

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Abstract

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgements

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.

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Author notes

  1. Insa Winzenborg and Ahmed Nader contributed equally to the pharmacokinetic model design and execution as well as to the writing of this manuscript.

Authors and Affiliations

  1. Clinical Pharmacology and Pharmacometrics, Department R4PK, AbbVie Inc., Building AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA

    Insa Winzenborg, Ahmed Nader, Akshanth R. Polepally, Mohan Liu, Jacob Degner, Cheri E. Klein, Nael M. Mostafa, Peter Noertersheuser & Juki Ng

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  1. Insa Winzenborg
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  2. Ahmed Nader
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  9. Juki Ng
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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

Correspondence to Ahmed Nader.

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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.

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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

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  • DOI: https://doi.org/10.1007/s40262-018-0629-6

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