The clinical pharmacology of elagolix was extensively evaluated in clinical 
studies in healthy subjects and in women with endometriosis. Elagolix 
pharmacokinetics (PK) show significant population variability, however they are 
minimally affected by patients' baseline characteristics and demographics, 
except for clinically relevant extrinsic and intrinsic factors such as 
coadministrated strong organic anion transporting polypeptide (OATP) 1B1 
inhibitors and severe hepatic impairment, which are contraindications for the 
use of elagolix. These studies enabled a comprehensive understanding of elagolix 
mechanism of action and the downstream pharmacodynamic (PD) effects on 
gonadotropin and ovarian hormones, as well as full characterization of the PK/PD 
(PKPD) relationships of elagolix at various dosages, including the approved 
150 mg once daily and 200 mg twice daily dosing regimens for the management of 
moderate to severe pain associated with endometriosis. Several model-based 
analyses have contributed to understanding of the benefit-risk profile of 
elagolix in patients with endometriosis, through characterization of the 
exposure relationship with responder rates, with changes in bone mineral density 
over time, as well as the interaction with coadministered drugs. Collectively, 
these studies and analyses served as supportive evidence for the effectiveness 
of the approved dosages and provided general dosing instructions of the first 
approved oral gonadotropin-releasing hormone receptor antagonist.