Treatment of endometriosis-associated pain with linzagolix, an oral gonadotropin-releasing hormone-antagonist: a randomized clinical trial

Fertil Steril. 2020 Jul;114(1):44-55. doi: 10.1016/j.fertnstert.2020.02.114. Epub 2020 Jun 4.

Abstract

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Carboxylic Acids / administration & dosage*
  • Carboxylic Acids / adverse effects
  • Chronic Pain / drug therapy*
  • Chronic Pain / etiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endometriosis / complications*
  • Endometriosis / drug therapy
  • Female
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Hormone Antagonists / administration & dosage*
  • Hormone Antagonists / adverse effects
  • Humans
  • Middle Aged
  • Pelvic Pain / drug therapy*
  • Pelvic Pain / etiology*
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Treatment Outcome
  • Uterine Diseases / complications*
  • Uterine Diseases / drug therapy
  • Young Adult

Substances

  • Carboxylic Acids
  • Hormone Antagonists
  • OBE2109
  • Pyrimidines
  • Gonadotropin-Releasing Hormone
  • linzagolix

Associated data

  • ClinicalTrials.gov/NCT02778399