Elagolix Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis
Condition: Endometriosis
MeSH terms: Endometriosis
Intervention: Elagolix; Subcutaneous depot medroxyprogesterone acetate (DMPA-SC); Placebo to Elagolix; Placebo to DMPA-SC
Intervention description: Provided as tablets for oral administration; Provided for subcutaneous injection in a prefilled syringe, 104 mg/0.65 mL per syringe.; Matching placebo tablets for oral administration; Matching placebo for subcutaneous injection in a pre-filled syringe
Intervention MeSH terms: Medroxyprogesterone Acetate; Medroxyprogesterone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 252.0
Sex: Female
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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