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

NCT03343067 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: M16-383
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 37

Brief Summary

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.

Conditions

Endometriosis

Keywords

Endometriosis associated pain; Elagolix; Non-menstrual pelvic pain (NMPP); Dysmenorrhea (DYS)

Outcome Measures

Primary Outcomes (2)

• Proportion of Responders at Month 6 Based on DYS Pain Scale

  Proportion of responders at Month 6 based upon the scale for DYS pain scale (ranging from 0 \[none\] to 3 \[severe\]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.

  Month 6

• Proportion of Responders at Month 6 Based on NMPP Pain Scale

  Proportion of responders at Month 6 based upon the scale for NMPP pain scale (ranging from 0 \[none\] to 3 \[severe\]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.

  Month 6

Secondary Outcomes (38)

• Change From Baseline in DYS at Month 6

  Month 0 (baseline), Month 6

• Change From Baseline in NMPP at Month 6

  Month 0 (baseline), Month 6

• Change From Baseline in Dyspareunia at Month 6

  Month 0 (baseline), Month 6

• Change From Baseline in Daily Diary Endometriosis-Associated Pain Score Via Numeric Rating Scale (NRS) at Month 6

  Month 0 (baseline), Month 6

• Change From Baseline in Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) at Month 6

  Month 0 (baseline), Month 6

Study Arms (4)

Arm A

EXPERIMENTAL

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

Drug: elagolix

Arm C

EXPERIMENTAL

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.

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

Arm D

EXPERIMENTAL

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.

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

Arm B

EXPERIMENTAL

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.

Drug: elagolix

Interventions

elagolix DRUG

Tablets

Arm A; Arm B; Arm C; Arm D

estradiol/norethindrone acetate (E2/NETA) DRUG

Capsules

Arm C; Arm D

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• At least 2 days of "moderate" or "severe" DYS, AND either,
• At least 2 days of "moderate" or "severe" NMPP and an average NMPP score of at least 1.0, OR
• At least 4 days of "moderate" or "severe" NMPP and an average NMPP score of at least 0.5.

You may not qualify if:

• 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
• 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
• a clinically significant medical condition that is anticipated to required intervention during the course of study participation (e.g., anticipated major elective surgery) OR
• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (37)

Pinnacle Research Group /ID# 202016

Anniston, Alabama, 36207, United States

Location

Noble Clinical Research /ID# 170628

Tucson, Arizona, 85704, United States

Location

Lynn Institute of the Ozarks /ID# 165052

Little Rock, Arkansas, 72205, United States

Location

SC Clinical Research /ID# 165049

Garden Grove, California, 92844, United States

Location

Marvel Clinical Research /ID# 169633

Huntington Beach, California, 92647, United States

Location

Health care Affiliates Medical Group /ID# 165048

Santa Ana, California, 92704, United States

Location

Western States Clinical Res /ID# 169809

Wheat Ridge, Colorado, 80033-2896, United States

Location

Nova Clinical Research, LLC /ID# 202227

Bradenton, Florida, 34209-4616, United States

Location

Midland Florida Clinical Research Center /ID# 201327

DeLand, Florida, 32720-0920, United States

Location

Southeastern Integrated Med /ID# 203109

Gainesville, Florida, 32607, United States

Location

Care Partners Clinical Researc /ID# 168395

Jacksonville, Florida, 32277, United States

Location

LCC Medical Research Institute /ID# 168888

Miami, Florida, 33126, United States

Location

A Premier Clinical Research of Florida, LLC /ID# 201887

Orange City, Florida, 32763-2833, United States

Location

GCP Clinical Research, LLC /ID# 169774

Tampa, Florida, 33609-4044, United States

Location

Triple O Research Institute /ID# 201128

West Palm Beach, Florida, 33407-3100, United States

Location

Bingham Memorial Hospital /ID# 170110

Blackfoot, Idaho, 83221, United States

Location

Leavitt Womens Healthcare /ID# 169495

Idaho Falls, Idaho, 83404-8322, United States

Location

Quad Clinical Research, LLC /ID# 168294

Chicago, Illinois, 60605, United States

Location

Quad Clinical Research, LLC /ID# 170629

Chicago, Illinois, 60605, United States

Location

Women's Health Care, PC /ID# 165033

Newburgh, Indiana, 47630-8940, United States

Location

Delricht Research /ID# 200219

New Orleans, Louisiana, 70115, United States

Location

Quad Clinical Research, LLC /ID# 200180

St Louis, Missouri, 63108-3204, United States

Location

Montana Health Research Inst /ID# 170624

Billings, Montana, 59102, United States

Location

Excel Clinical Research /ID# 170620

Las Vegas, Nevada, 89109, United States

Location

Northwell health system /ID# 200162

Manhasset, New York, 11030-3816, United States

Location

Radiant Research, Inc /ID# 200045

Akron, Ohio, 44311, United States

Location

Central Ohio Clinical Research /ID# 170750

Columbus, Ohio, 43213-3399, United States

Location

Optimed Research /ID# 167642

Columbus, Ohio, 43235, United States

Location

VitaLink Research /ID# 168401

Greenville, South Carolina, 29601, United States

Location

VitaLink Research /ID# 170625

Greenville, South Carolina, 29601, United States

Location

Fusion Clinical Research of Spartanburg /ID# 200010

Spartanburg, South Carolina, 29301-5642, United States

Location

Centex Studies, Inc /ID# 169897

Houston, Texas, 77058-2705, United States

Location

America's Adv. Wellness Center /ID# 170005

Houston, Texas, 77080, United States

Location

ClinRx Research, LLC /ID# 201189

Plano, Texas, 75024-5280, United States

Location

Progressive Clinical Research /ID# 205565

San Antonio, Texas, 78229, United States

Location

Eastern Virginia Med School /ID# 165016

Norfolk, Virginia, 23507-1627, United States

Location

Seattle Reproductive Medicine /ID# 171079

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Endometriosis; Dysmenorrhea

Interventions

elagolix; Estradiol; Norethindrone Acetate

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pelvic Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norethindrone; Norpregnenes; Norpregnanes; Norsteroids

Limitations and Caveats

Due to early study termination at Treatment Month 6 with low subject enrollment, no clinically or statistically meaningful efficacy conclusions can be made. The study was terminated early for business reasons, not for safety concerns.

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: November 17, 2017
• Study Start: December 27, 2017
• Primary Completion: October 23, 2018
• Study Completion: October 23, 2018
• Last Updated: November 27, 2019
• Results First Posted: November 27, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.

Locations

US (37)