A Clinical Study to Evaluate the Safety and Efficacy of Elagolix in Participants With Moderate to Severe Endometriosis-Associated Pain
Condition: Endometriosis
MeSH terms: Endometriosis
Intervention: Estradiol/Norethindrone Acetate; Placebo for Elagolix; Elagolix; Placebo for E2/NETA
Intervention description: Tablets; Tablet; Tablet; Tablets
Intervention MeSH terms: Norethindrone; Norethindrone Acetate; Estradiol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 681.0
Sex: Female
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: No
Keywords: Elagolix; Endometriosis associated pain; Dysmenorrhea (DYS); Non-menstrual pelvic pain (NMPP); ORILISSA

Summary:

      The objective of this study is to evaluate safety and efficacy of elagolix in the management
      of moderate to severe endometriosis-associated pain in adult premenopausal female
      participants including the safety and efficacy of elagolix in combination with concomitant
      hormonal add-back therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant is a premenopausal female 18 to 49 years of age (inclusive) at the time of
             Screening.

          -  Participant has a documented surgical diagnosis (e.g., laparoscopy or laparotomy) of
             endometriosis established by visualization within 10 years prior to entry into Washout
             or Screening.

          -  Participant must agree to use only protocol specified rescue analgesics during the
             Screening and Treatment Periods for endometriosis-associated pain.

          -  Participant must have the following documented in the e-Diary during the last 35 days
             prior to Study Day 1:

               1. At least 2 days of "moderate" or "severe" dysmenorrhea (DYS) AND either

               2. At least 2 days of "moderate" or "severe" non-menstrual pelvic pain (NMPP) and an
                  average NMPP score of at least 1.0, OR

               3. At least 4 days of "moderate" or "severe" NMPP and an average NMPP score of at
                  least 0.5.

        Exclusion Criteria:

          -  Participant has chronic pelvic pain that is not caused by endometriosis, that requires
             chronic analgesic therapy, which would interfere with the assessment of
             endometriosis-related pain.

          -  Participant is using any systemic corticosteroids for over 14 days within 3 months
             prior to Screening or is likely to require treatment with systemic corticosteroids
             during the course of the study. Over-the-counter and prescription topical, inhaled or
             intranasal corticosteroids are allowed.

          -  Participant has a history of any major depression or post-traumatic stress disorder
             (PTSD) within 2 years of the screening visit or other major psychiatric disorder at
             any time.

          -  Participant has a history of suicide attempts or answered "yes" to questions 4 or 5 on
             the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS)
             within the last 1 year at Screening or prior to randomization on Day 1.

          -  Participant has any history of osteoporosis or other metabolic bone disease or any
             condition that would interfere with obtaining adequate dual energy x-ray
             absorptiometry (DXA) measurements

          -  Screening DXA results of the lumbar spine (L1-L4), femoral neck or total hip bone
             mineral density (BMD) corresponding to less than 2.0 or more standard deviations below
             normal.

          -  Participant has either:

               1. a newly diagnosed, clinically significant medical condition that requires
                  therapeutic intervention (e.g., new onset hypertension), that has not been
                  stabilized 30 days prior to randomization on Day 1 OR

               2. a clinically significant medical condition that is anticipated to require
                  intervention during the course of study participation (e.g., anticipated major
                  elective surgery) OR

               3. an unstable medical condition that makes the subject an unsuitable candidate for
                  the study in the opinion of the Investigator, (including, but not limited to,
                  uncontrolled diabetes mellitus, uncontrolled hypertension, epilepsy requiring
                  anti-epileptic medication, unstable angina, confirmed inflammatory bowel disease,
                  hyperprolactinemia, clinically significant infection or injury).

          -  Participant has any conditions contraindicated with use of E2/NETA.