J. Ng, C. E. Klein, W. R. Duan, J. Yan, A. Kaefer, L. A. Williams; AbbVie, 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 renal function or renal impairment.
METHODS: This was an open-label study in which 15 females aged 37-59 received a single 200 mg oral dose of elagolix. Six subjects with normal renal function, three with moderate to severe renal impairment, and six with end-stage renal disease (ESRD) were enrolled. Intensive blood samples for elagolix assay were collected for 48 hours after dosing. Protein binding was determined, and safety data including adverse events, physical exam, vital signs, ECGs, and laboratory tests were collected. Values for maximum concentrations (Cmax), area-under-the-curve (AUC) and half-life were estimated using non-compartmental methods.
RESULTS: Elagolix Cmax and AUCs appeared to be similar between subjects with normal renal function and ESRD subjects, and slightly lower (~25%) in subjects with moderate to severe renal impairment. Half-life was comparable amongst the subject groups. No impact on protein binding of elagolix was noted as the unbound fractions were similar among subjects with normal renal function and those with renal impairment. The safety and tolerability profile of a single 200 mg dose of elagolix was acceptable in this study. No clinically significant changes attributable to study drug were observed in vital signs, ECGs and laboratory tests.
CONCLUSION: Renal impairment does not result in higher elagolix exposure or changes in protein binding. The mean elagolix exposure appeared to be similar in subjects with normal renal function and those with ESRD.