Volume 114, Issue 1, Pages 44–55
Jacques Donnez, M.D., Ph.D., Hugh S. Taylor, M.D., Ph.D., Robert N. Taylor, M.D., Ph.D., Mark D. Akin, M.D., Tatyana F. Tatarchuk, M.D., Dr. Sc., Krzysztof Wilk, M.D., Jean-Pierre Gotteland, Ph.D., Veronique Lecomte, Pharm.D., Elke Bestel, M.D.
To study the effect of a new investigational oral gonadotropin-releasing hormone antagonist, linzagolix, on endometriosis-associated pain (EAP).
A multinational, parallel group, randomized, placebo-controlled, double-blind, dose-ranging trial.
Women aged 18–45 years with surgically confirmed endometriosis and moderate-to-severe EAP.
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).
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.
Linzagolix significantly reduced EAP and improved QoL at doses of 75–200 mg and decreased BMD dose-dependently.