CONTEXT: Parenteral administration of peptide GnRH analogs is widely employed 
for treatment of endometriosis and fibroids and in assisted-reproductive therapy 
protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist.
OBJECTIVE: Our objective was to evaluate the safety, pharmacokinetics, and 
inhibitory effects on gonadotropins and estradiol of single-dose and 7-d 
elagolix administration to healthy premenopausal women.
DESIGN: This was a first-in-human, double-blind, placebo-controlled, single- and 
multiple-dose study with sequential dose escalation.
PARTICIPANTS: Fifty-five healthy, regularly cycling premenopausal women 
participated.
INTERVENTIONS: Subjects were administered a single oral dose of 25-400 mg or 
placebo. In a second arm of the study, subjects received placebo or 50, 100, or 
200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 
(+/-1) after onset of menses.
MAIN OUTCOME MEASURES: Safety, tolerability, pharmacokinetics, and serum LH, 
FSH, and estradiol concentrations were assessed.
RESULTS: Elagolix was well tolerated and rapidly bioavailable after oral 
administration. Serum gonadotropins declined rapidly. Estradiol was suppressed 
by 24 h in subjects receiving at least 50 mg/d. Daily (50-200 mg) or twice-daily 
(100 mg) administration for 7 d maintained low estradiol levels (17 +/- 3 to 68 
+/- 46 pg/ml) in most subjects during late follicular phase. Effects of the 
compound were rapidly reversed after discontinuation.
CONCLUSIONS: Oral administration of a nonpeptide GnRH antagonist, elagolix, 
suppressed the reproductive endocrine axis in healthy premenopausal women. These 
results suggest that elagolix may enable dose-related pituitary and gonadal 
suppression in premenopausal women as part of treatment strategies for 
reproductive hormone-dependent disease states.