Efficacy and Safety Study of Elagolix Versus Placebo or Leuprorelin Acetate in Endometriosis

A Phase II, Randomized, Double-Blind, Placebo- and Active-Controlled Study to Assess the Efficacy and Safety of NBI-56418 in Subjects With Endometriosis

This study is designed to evaluate the safety and beneficial effects of elagolix (NBI-56418) compared to placebo and leuprorelin (an approved endometriosis therapy) over a three month period followed by an additional three months of treatment on elagolix.

The study followed a parallel-group design in which participants were randomized (1:1:1:1) to one of the following treatment groups for the first 12 weeks of dosing: 150 mg elagolix once daily (q.d.); 250 mg elagolix q.d.; placebo; or leuprorelin acetate depot injection 3.75 mg (monthly). Blinding was achieved using a double-dummy design. Following 12 weeks of dosing, participants continued in the study for an additional 12 weeks; participants randomized to elagolix continued to receive their assigned dose and participants randomized to placebo or leuprorelin acetate were re-randomized to receive one of the two doses of elagolix (150 mg q.d. or 250 mg q.d.) for 12 weeks in a double-blind fashion. Six weeks after the last dose of the study drug at the end of Week 24, a follow-up visit was performed (end of Week 30).

There was no pre-specified primary efficacy end point as there was no single key efficacy outcome measure in this exploratory Phase 2 study. For purposes of results reported here, Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain is designated as the primary outcome measure.

Inclusion Criteria

• Female, aged 18 to 45 years, inclusive
• Have moderate to severe pelvic pain due to endometriosis
• Have been surgically (laparoscopy) diagnosed with endometriosis within the last 5 years and have recurrent or persistent endometriosis symptoms
• Have regular menstrual cycle (23-33 day)
• Agree to use two forms of non-hormonal contraception during the study

Exclusion Criteria:

• Received a Gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening.
• Received subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular (i.m.) medroxyprogesterone acetate (DMPA-IM), or have received either of these agents within 3 months of the start of screening.
• Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within the last month
• Have had surgery for endometriosis within the last month
• Are using systemic steroids on a chronic or regular basis within 3 months
• Have uterine fibroids or other pelvic lesions ≥ 3 cm in diameter
• Have had a hysterectomy or oophorectomy
• Have pelvic pain that is not caused by endometriosis
• Have unstable medical condition or chronic disease
• Have been pregnant within the last 6 months and is currently breast feeding