A Clinical Study to Evaluate the Safety and Efficacy of Elagolix in Participants With Moderate to Severe Endometriosis-Associated Pain

AbbVie

Status and phase: Completed; Phase 3

Conditions: Endometriosis

Treatments: Drug: Placebo for E2/NETA; Drug: Estradiol/Norethindrone Acetate; Drug: Elagolix; Drug: Placebo for Elagolix

Study type: Interventional

Funder types: Industry

Identifiers

NCT03213457

M14-702

Details and patient eligibility

About

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.

Enrollment: 681 patients

Sex: Female

Ages: 18 to 49 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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681 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo for elagolix administered twice daily (BID) plus placebo for estradiol/norethindrone acetate (E2/NETA) administered once daily (QD) for the 12-month placebo-controlled Treatment Period, followed by elagolix 200 mg BID plus E2/NETA 1 mg/0.5 mg QD for the remaining 36 months of the Treatment Period.

Treatment:

Drug: Placebo for Elagolix

Drug: Placebo for E2/NETA

Elagolix / Elagolix + E2/NETA

Experimental group

Description:

Elagolix 200 mg BID alone for the first 6 months of the 12-month placebo-controlled Treatment Period and elagolix 200 mg BID+E2/NETA 1 mg/0.5 mg QD for the second 6 months, followed by elagolix 200 mg BID+E2/NETA 1 mg/0.5 mg QD for the remaining 36 months of the Treatment Period.

Treatment:

Drug: Elagolix

Drug: Estradiol/Norethindrone Acetate

Elagolix + E2/NETA

Experimental group

Description:

Elagolix 200 mg BID + E2/NETA 1 mg/0.5 mg QD for the 12-month placebo-controlled Treatment Period, followed by elagolix 200 mg BID plus E2/NETA 1 mg/0.5 mg QD for the remaining 36 months of the Treatment Period.

Treatment:

Drug: Elagolix

Drug: Estradiol/Norethindrone Acetate