CONTEXT: Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) 
antagonist being developed for sex-hormone-dependent diseases in women.
OBJECTIVE: We evaluated the pharmacokinetics and pharmacodynamics of elagolix.
DESIGN, SETTING, AND PARTICIPANTS: This study was a randomized, double-blind, 
placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal 
women at a research unit.
INTERVENTIONS: Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice 
daily (BID)] or placebo was administered for 21 days.
MAIN OUTCOME MEASURES: Main outcome measures were elagolix pharmacokinetics, 
suppression of gonadotropics [follicle-stimulating hormone (FSH), luteinizing 
hormone (LH)] and ovarian hormones [estradiol (E2), progesterone (P)], and 
adverse events.
RESULTS: Elagolix was rapidly absorbed after oral dosing, reaching maximum 
concentrations at 1.0 to 1.5 hours, with a half-life of 4 to 6 hours. FSH, LH, 
and E2 were suppressed within hours of elagolix administration on day 1. 
Dose-dependent suppression of E2 was observed, with maximum suppression achieved 
with elagolix 200 mg BID. Dose-dependent suppression of FSH and LH was also 
observed, with maximal or near-maximal suppression achieved at 300 mg BID and 
200 mg BID, respectively. At elagolix doses ≥100 mg BID, P concentrations 
remained at anovulatory levels throughout 21 days of dosing. The most frequently 
reported adverse events were headache and hot flush.
CONCLUSIONS: Elagolix administration allows for modulation of gonadotropin and 
ovarian hormone concentrations, from partial suppression at lower doses to 
nearly full suppression at higher doses. The results of this study provide a 
rationale for elagolix dose selection for treatment of sex hormone-dependent 
diseases in women.