J. Ng, C. E. Klein, W. R. Duan, J. Yan, L. A. Williams; AbbVie Inc., North Chicago, IL
BACKGROUND: This study was designed to assess the pharmacokinetics and safety of a single dose of elagolix (a novel oral GnRH antagonist currently in development for the management of endometriosis and uterine fibroids in premenopausal women) in female subjects with normal hepatic function and hepatic impairment.
METHODS: This is an open-label study in which 22 female subjects aged 46-61 received a single 150 mg oral dose of elagolix. Six subjects with normal hepatic function, 16 with hepatic impairment (6 mild, 6 moderate, and 4 severe based on the Child-Pugh Classification) were enrolled. Intensive blood samples for elagolix assay were collected up to 72 hours after dosing. Safety data, including adverse event monitoring, physical exam, vital signs, ECGs, and laboratory tests were collected during the study. Values for elagolix maximum concentrations (Cmax) and area-under-the-curve (AUC) were estimated.
RESULTS: Elagolix Cmax and AUCs for subjects with mild, moderate, and severe hepatic impairment were approximately 20% lower, 2.6- and 2.7-fold, and 6- and 7-fold higher, respectively, than subjects with normal hepatic function. The safety profile of a single elagolix dose was acceptable in this study. No clinically significant changes in laboratory values, vital signs or ECGs attributable to study drug were observed. One death (20 days after single dose) was considered not to be related to study drug, but rather, a complication of chronic alcohol abuse with alcoholic cirrhosis.
CONCLUSION: Elagolix exposure appeared to be similar between subjects with normal hepatic function and those with mild hepatic impairment. Elagolix exposure increased by approximately 3-fold in subjects with moderate hepatic impairment and approximately 7‑fold in subjects with severe hepatic impairment.