OBJECTIVE: To study the effect of a new investigational oral gonadotropin-releasing hormone antagonist, linzagolix, on endometriosis-associated pain (EAP).
DESIGN: A multinational, parallel group, randomized, placebo-controlled, double-blind, dose-ranging trial.
SETTING: Clinical centers.
PATIENT(S): Women aged 18-45 years with surgically confirmed endometriosis and moderate-to-severe EAP.
INTERVENTION(S): The interventions were 50, 75, 100, or 200 mg linzagolix (or matching placebo) administered once daily for 24 weeks.
MAIN OUTCOME MEASURE(S): The primary endpoint was the number of responders (≥30% reduction in overall pelvic pain) after 12 weeks. Other endpoints included dysmenorrhea, non-menstrual pelvic pain, serum estradiol, amenorrhea, quality of life (QoL) measures, and bone mineral density (BMD).
RESULT(S): Compared with placebo, doses ≥ 75 mg resulted in a significantly greater proportion of responders for overall pelvic pain at 12 weeks (34.5%, 61.5%, 56.4%, and 56.3% for placebo, 75, 100, and 200 mg, respectively). A similar pattern was seen for dysmenorrhea and non-menstrual pelvic pain. The effects were maintained or increased at 24 weeks. Serum estradiol was suppressed, QoL improved, and the rate of amenorrhea increased in a dose-dependent fashion. Mean BMD loss (spine) at 24 weeks was <1% at doses of 50 and 75 mg and increased in a dose-dependent fashion up to 2.6% for 200 mg. BMD of femoral neck and total hip showed a similar pattern.
CONCLUSION(S): Linzagolix significantly reduced EAP and improved QoL at doses of 75-200 mg and decreased BMD dose-dependently.
CLINICAL TRIAL REGISTRATION NUMBER: NCT02778399.
Keywords: BMD Endometriosis-associated pain GnRH antagonist linzagolix