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

AbbVie

Status and phase: Terminated; Phase 3

Conditions: Endometriosis

Treatments: Drug: estradiol/norethindrone acetate (E2/NETA); Drug: elagolix

Study type: Interventional

Funder types: Industry

Identifiers

NCT03343067

M16-383

Details and patient eligibility

About

This is a Phase 3, dose-escalation study designed to evaluate the safety and efficacy of both elagolix alone and elagolix plus estradiol/norethindrone acetate (E2/NETA) over 24 months in the management of endometriosis with associated moderate to severe pain in premenopausal women.

Enrollment: 11 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 or histology within 10 years prior to entry into Washout or Screening,

• Participant must agree to use only those rescue analgesics permitted by the protocol during the Screening and Treatment Periods for her 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" DYS, AND either,
  2. At least 2 days of "moderate" or "severe" 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-associated 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 major depression or post-traumatic stress disorder (PTSD) within 2 years prior to screening 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) at Screening or prior to study drug dosing on Day 1.

• Participant has 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 or more standard deviations below normal (Z-score < -2.0 for participants < 40 years of age, T-score for participants >= 40 years of age).

• 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 enrollment on Day 1 OR
  2. a clinically significant medical condition that is anticipated to required intervention during the course of study participation (e.g., anticipated major elective surgery) OR
  3. an unstable medical condition that makes the participant an unsuitable candidate for the study in the opinion of the Investigator

• 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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11 participants in 4 patient groups

Arm A

Experimental group

Description:

Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 24 (Double-Blind): Efficacy responders to elagolix 150 mg QD at Month 3 and continue treatment through Month 24

Treatment:

Drug: elagolix

Arm C

Experimental group

Description:

Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 24 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group and continue treatment through Month 24.

Treatment:

Drug: elagolix

Drug: estradiol/norethindrone acetate (E2/NETA)

Arm D

Experimental group

Description:

Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 150 mg QD treatment group Month 7 Through Month 24 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 6 and assigned to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group and continue treatment through Month 24.

Treatment:

Drug: elagolix

Drug: estradiol/norethindrone acetate (E2/NETA)

Arm B

Experimental group

Description:

Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 150 mg QD treatment group Month 7 Through Month 24 (Double-Blind): Efficacy responders to elagolix 150 mg QD at Month 6 and continue treatment through Month 24.

Treatment:

Drug: elagolix