Elagolix Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis

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

This study is designed to assess the effects of elagolix versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC; also known as depo-provera) on bone mineral density (BMD) during treatment for 24 weeks with a subsequent 24-week post-treatment period.

Inclusion Criteria:

• Be female, aged 18 to 49 years, inclusive
• Have a total CPSSS of ≥ 6 at screening and baseline (Day 1) in the following categories: dysmenorrhea, dyspareunia, nonmenstrual pelvic pain, pelvic tenderness and induration. The total score must include a total of at least 2 in each of the categories of dysmenorrhea and nonmenstrual pelvic pain.
• Have had a diagnosis of endometriosis made following laparoscopic visualization of the disease within 8 years of the start of screening with recurrent or persistent symptoms.
• Have documented negative mammogram results within 12 months of screening if over the age of 40 years.
• Have menstrual cycles (28 days ±5 days). Assessment of cycle duration should be based on observations in the absence of drugs or conditions that are known to affect the cycle (e.g., oral contraceptives, leuprolide, pregnancy).
• Have a Body Mass Index (BMI) between 18 and 36 kg/m², inclusive.
• Agree to use two forms of nonhormonal contraception (e.g. condom with spermicide) during the study.

Exclusion Criteria:

• Are currently receiving gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening.

• Are currently receiving subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular medroxyprogesterone acetate (DMPA-IM) or have received any of these agents within 3 months of the start of screening.

• Have been nonresponsive to GnRH agonist or antagonist therapy for the management of endometriosis.

• Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within 1 month of the start of screening.

• Have had surgical treatment for endometriosis (laparoscopy) within 1 month of the start of screening.

• Have had a hysterectomy or bilateral oophorectomy.

• Have had prior treatment with NBI-56418.

• Have uterine fibroids or other pelvic lesions ≥ 5 cm in diameter

• Have any of the following abnormal cervical smear results at screening (based on the 2001 Bethesda System):

  • Benign endometrial cells (BEC) present, provided subject has irregular uterine bleeding or is over 40 years old
  • Atypical squamous cells of undetermined significance (ASC-US) present, and human papilloma virus (HPV) reflex testing is positive for high risk types or the testing outcome is unknown
  • Atypical squamous cells present, and high-grade squamous intraepithelial lesion (ASC-H) cannot be excluded
  • Atypical glandular cells of uncertain significance (AGUS/AGC): not otherwise specified (NOS), favor neoplasia (FN), favor endocervical, or favor endometrial origin types
  • Low-grade squamous intraepithelial lesion (LSIL) present
  • High-grade squamous intraepithelial lesion (HSIL) present
  • Adenocarcinoma in situ (AIS) / malignant cells present

• Have BMD with either lumbar spine or femur T-scores below -1.5 at screening as determined by the central DXA facility or have history of pathologic or compression fractures.

• Have been pregnant within 6 months of screening or currently breast feeding

• Are using systemic steroids on a chronic or regular basis within 3 months

• Have unstable medical condition or chronic disease

• Have chronic pelvic pain that is not caused by endometriosis