This study elucidates kinetic and dynamic properties of elagolix, an oral GnRH antagonist. Authors find that elagolix suppresses LH/FSH and Estradiol/Progestorone fully at respective doses of 300 mg and 200 mg BID. As expected the main side effects were hot flashes and headaches (induced menopausal symptoms). A group of 45 healthy premenopausal women were followed for 21 days.
Estrogen/ovarian suppression is needed in certain medical conditions such as hormone-dependent breast carcinomas.
GT
J C E M
Randomized Trial
May 2017
Context: Elagolix is an oral nonpeptide 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) or placebo was administered for 21 days.
Main Outcome Measures:
Main outcome measures were elagolix pharmacokinetics, gonadotropics (FSH and LH) and ovarian hormones (estradiol and progesterone) suppression and adverse events.
Results:
Elagolix was rapidly absorbed after oral dosing, reaching maximum concentrations at 1.0-1.5 hours, with a half-life of 4-6 hours. FSH, LH, and E2 were suppressed within hours of elagolix administration on day one.
Dose-dependent suppression of estradiol 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, progesterone 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.