Efficacy and Safety of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women

A Phase 3 Study to Evaluate the Efficacy and Safety of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women

This study seeks to evaluate the efficacy, safety and tolerability of elagolix alone and in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Study Overview

• Status: Completed
• Conditions: Uterine Fibroids; Heavy Menstrual Bleeding
• Intervention / Treatment: Drug: Placebo for Estradiol/Norethindrone Acetate; Drug: Placebo for Elagolix; Drug: Elagolix; Drug: Estradiol/Norethindrone Acetate

• Study Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Center /ID# 149066
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital /ID# 148695
• Puerto Rico
  • San Juan, Puerto Rico, 00917
    • Rodriguez-Ginorio, San Juan /ID# 139847
  • San Juan, Puerto Rico, 00935
    • School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 139848
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Summers, Birmingham, AL /ID# 139684
    • Mobile, Alabama, United States, 36604-3302
      • University of South Alabama /ID# 148763
  • California
    • Costa Mesa, California, United States, 92626
      • WCCT Global, LLC /ID# 145666
    • Hawaiian Gardens, California, United States, 90716
      • American Clinical Trials /ID# 147374
    • La Mesa, California, United States, 91942
      • Grossmont Ctr Clin Research /ID# 144011
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trial Serv /ID# 152424
    • Los Angeles, California, United States, 90057
      • National Research Institute /ID# 151629
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles /ID# 144107
    • Newport Beach, California, United States, 92663-3657
      • Beach OBGYN Medical Group /ID# 151414
    • Westminster, California, United States, 92683-4567
      • Advanced RX Clinical Research /ID# 149168
  • Colorado
    • Colorado Springs, Colorado, United States, 80923
      • Bluebird Clinical Trials, LLC /ID# 144843
    • Greenwood Village, Colorado, United States, 80111
      • Advanced Women's Health Institution /ID# 144108
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Health Research Institute /ID# 145933
    • Washington, District of Columbia, United States, 20036
      • James A. Simon, MD, PC /ID# 139675
  • Florida
    • Boynton Beach, Florida, United States, 33436-6634
      • Helix Biomedics, LLC /ID# 147114
    • Brandon, Florida, United States, 33510-3107
      • Brandon Premier Health Care, PA /ID# 153130
    • Ckearwater, Florida, United States, 33759
      • Florida Clin Res Group /ID# 139811
    • Doral, Florida, United States, 33166
      • Universal Clinical Research A /ID# 139742
    • Fort Myers, Florida, United States, 33912
      • Clinical Physiology Associates /ID# 139736
    • Kenneth City, Florida, United States, 33709-3113
      • Meridien Research /ID# 139663
    • Lake Worth, Florida, United States, 33461
      • Altus Research, Inc /ID# 139662
    • Margate, Florida, United States, 33063
      • South Florida Wellness & Clinic /ID# 143558
    • Miami, Florida, United States, 33126
      • LCC Medical Research Institute /ID# 143551
    • Miami, Florida, United States, 33161
      • Healthcare Clinical Data, Inc /ID# 139650
    • Miami, Florida, United States, 33166
      • Ocean Blue Med Research Ctr /ID# 139826
    • Miramar, Florida, United States, 33027
      • Salom Tangir, LLC /ID# 151732
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute /ID# 143554
    • Orlando, Florida, United States, 32806
      • Clinical Associates of Orlando /ID# 148123
    • Orlando, Florida, United States, 32810
      • Omega Research Consultants /ID# 139648
    • Panama City, Florida, United States, 32045
      • Unified Womens Clin Research /ID# 145169
    • West Palm Beach, Florida, United States, 33409
      • Comprehensive Clinical Trials /ID# 139644
  • Georgia
    • Alpharetta, Georgia, United States, 30005-4419
      • Atlanta Medical Research Insti /ID# 147117
    • Alpharetta, Georgia, United States, 30005
      • Paramount Research Solutions /ID# 139645
    • Atlanta, Georgia, United States, 30328
      • Agile Clinical Research Trials /ID# 143563
    • Atlanta, Georgia, United States, 30338
      • Perimeter Inst Clinical Resear /ID# 148298
    • Augusta, Georgia, United States, 30909
      • Masters of Clinical Research, Inc. /ID# 139658
    • Savannah, Georgia, United States, 31406
      • Fellows Research Alliance, Inc /ID# 139655
  • Idaho
    • Boise, Idaho, United States, 83709
      • Boise Family Medical Center /ID# 139844
  • Illinois
    • Champaign, Illinois, United States, 61820
      • Women's Health Practice, LLC /ID# 143569
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials /ID# 148135
    • Oak Brook, Illinois, United States, 60523
      • Affinity Clinical Research /ID# 150980
  • Indiana
    • Avon, Indiana, United States, 46123
      • American Health Network of IN /ID# 139822
  • Kansas
    • Kansas City, Kansas, United States, 66218
      • GTC Research /ID# 141854
    • Wichita, Kansas, United States, 67226
      • Cypress Medical Research Ctr /ID# 147116
  • Kentucky
    • Owensboro, Kentucky, United States, 42303-1089
      • Research Integrity, LLC /ID# 139727
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Clinical Trials Management, LLC - Covington /ID# 139651
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Baptist Medical Center /ID# 139740
    • Shreveport, Louisiana, United States, 71118
      • Omni Fertility and Laser Insti /ID# 139836
  • Maryland
    • Frederick, Maryland, United States, 21708
      • Capital Women's Care /ID# 144109
  • Massachusetts
    • Fall River, Massachusetts, United States, 02723
      • Genesis Clinical Research - Fall River /ID# 148449
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group,Inc /ID# 139659
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Womens Health /ID# 139705
    • Southfield, Michigan, United States, 48034
      • Wayne State University Physician Group - Southfield /ID# 139802
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Office of Edmond E. Pack, MD /ID# 139792
    • Las Vegas, Nevada, United States, 89128
      • Mabey, Las Vegas, NV /ID# 148138
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrence OB/GYN /ID# 143567
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Bosque Women's Care /ID# 145934
  • New York
    • New York, New York, United States, 10016-6023
      • Manhattan Medical Research /ID# 144471
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Cwrwc /Id# 139664
    • Greensboro, North Carolina, United States, 27408
      • Unified Women's Clinical Research-Greensboro /ID# 139829
    • Raleigh, North Carolina, United States, 27607
      • Unified Women's Clinical Resea /ID# 139774
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington LLC /ID# 152563
    • Winston-Salem, North Carolina, United States, 27103
      • Unified Women's Clinical Resea /ID# 144721
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0585
      • University of Cincinnati /ID# 139820
    • Cleveland, Ohio, United States, 44106
      • Univ Hosp Cleveland /ID# 139741
    • Columbus, Ohio, United States, 43231
      • Complete Healthcare for Women /ID# 139673
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital /ID# 144430
    • Toledo, Ohio, United States, 43614
      • University of Toledo /ID# 139787
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Medical Group-Portland /ID# 148807
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Main Line Fertility Center /ID# 150295
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University and Milton S. Hershey Medical Center /ID# 139733
    • Philadelphia, Pennsylvania, United States, 19107-4414
      • Thomas Jefferson University /ID# 139812
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital /ID# 151429
    • Pittsburgh, Pennsylvania, United States, 15206
      • Clinical Trials Research Svcs /ID# 139707
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina /ID# 148754
    • Columbia, South Carolina, United States, 29201
      • Vista Clinical Research /ID# 139797
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421-1605
      • WR-ClinSearch /ID# 143538
    • Memphis, Tennessee, United States, 38119-3895
      • Research Memphis Associates, LLC /ID# 139674
    • Nashville, Tennessee, United States, 37203
      • Access Clinical Trials, Inc. /ID# 139730
  • Texas
    • Dallas, Texas, United States, 75390-7208
      • UT Southwestern Medical Center /ID# 143537
    • Houston, Texas, United States, 77030
      • Advances in Health, Inc. /ID# 139672
    • San Antonio, Texas, United States, 78230
      • Victorium Clinical Research /ID# 149630
    • San Antonio, Texas, United States, 78258
      • Discovery Clinical Trials-San Antonio /ID# 139776
    • Sugar Land, Texas, United States, 77479
      • Houston Ctr for Clin Research /ID# 149149
    • Webster, Texas, United States, 77598
      • Center of Reproductive Medicin /ID# 139813
  • Virginia
    • Norfolk, Virginia, United States, 23507-1627
      • Eastern Virginia Med School /ID# 139647
    • North Chesterfield, Virginia, United States, 23235-4722
      • Clinical Research Partners, LL /ID# 143999
    • Richmond, Virginia, United States, 23225
      • Clinical Trials Virginia, Inc. /ID# 139801
    • Vienna, Virginia, United States, 22182
      • Emerson Clinical Research /ID# 147373
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Women's Health, Research, Gynecology /ID# 139768
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research /ID# 148145
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Froedtert and Medical College /ID# 143566

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subject is a premenopausal female at the time of Screening.
• Subject has a diagnosis of uterine fibroids documented by a pelvic ultrasound (transabdominal ultrasound/transvaginal ultrasound).
• Subject has heavy menstrual bleeding associated with uterine fibroids as evidenced by menstrual blood loss > 80 mL during each of two screening menses as measured by the alkaline hematin method.
• Subject has negative urine and/or serum pregnancy test in Screening and just prior to first dose.
• Subject has an adequate endometrial biopsy performed during Screening, the results of which show no clinically significant endometrial pathology.

Exclusion Criteria:

• Subject has screening pelvic ultrasound or saline infusion sonohysterography results that show a clinically significant gynecological disorder.
• Subject has history of osteoporosis or other metabolic bone disease.
• Subject has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.
• Subject has a history of major depression or post-traumatic stress disorder (PTSD) within 2 years of screening, OR a history of other major psychiatric disorder at any time (e.g., schizophrenia, bipolar disorder).
• Subject 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, intranasal or injectable (for occasional use) corticosteroids are allowed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo for both elagolix twice daily (BID) and norethindrone acetate (E2/NETA) once daily (QD)	Drug: Placebo for Estradiol/Norethindrone Acetate; Placebo capsules; Drug: Placebo for Elagolix; Film-coated placebo tablets
Experimental: Elagolix; Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD	Drug: Placebo for Estradiol/Norethindrone Acetate; Placebo capsules; Drug: Elagolix; Film-coated tablets; Other Names: ABT-620; elagolix sodium
Experimental: Elagolix + E2/NETA; Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD	Drug: Elagolix; Film-coated tablets; Other Names: ABT-620; elagolix sodium; Drug: Estradiol/Norethindrone Acetate; Commercially-available E2/NETA tablets were over-encapsulated to maintain study blinding.; Other Names: E2/NETA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Meeting the Criteria for Responder	Percentage of responders, defined as participants who met the following conditions: Menstrual blood loss (MBL) volume < 80 mL during the Final Month (the last 28 days prior to and including the Reference Day, which is defined as the last visit date during the Treatment Period [last treatment visit date] or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date), and; ≥ 50% reduction in MBL volume from Baseline to the Final Month. Participants who prematurely discontinued study drug due to "lack of efficacy," "requires surgery or invasive intervention for treatment of uterine fibroids," or "adverse events" were considered non-responders regardless of whether she meets the two aforementioned responder criteria or not.	Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in MBL Volume to the Final Month	Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.	Month 0 (Baseline), Final Month (the last 28 days prior to and including the Reference Day), up to Month 6
Percentage of Participants With Suppression of Bleeding at the Final Month	Suppression of bleeding is defined as having 0 days of bleeding (spotting is allowed) during the Final Month with the interval starting from Study Day 11. The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.	Final Month (the last 28 days prior to and including the Reference Day), up to Month 6
Change From Baseline in MBL Volume to Month 6		Month 0 (Baseline), Month 6
Change From Baseline in MBL Volume to Month 3		Month 0 (Baseline), Month 3
Percentage of Participants With Baseline Hemoglobin <= 10.5 g/dL Who Have an Increase in Hemoglobin > 2 g/dL at Month 6		Month 0 (Baseline), Month 6
Change From Baseline in MBL Volume to Month 1		Month 0 (Baseline), Month 1

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Beck D, Winzenborg I, Liu M, Degner J, Mostafa NM, Noertersheuser P, Shebley M. Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids. Clin Pharmacokinet. 2022 Apr;61(4):577-587. doi: 10.1007/s40262-021-01096-w. Epub 2021 Dec 8.
• Stewart EA, Archer DF, Owens CD, Barnhart KT, Bradley LD, Feinberg EC, Gillispie-Bell V, Imudia AN, Liu R, Kim JH, Al-Hendy A. Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids. J Womens Health (Larchmt). 2022 May;31(5):698-705. doi: 10.1089/jwh.2021.0152. Epub 2021 Sep 28.
• Muneyyirci-Delale O, Archer DF, Owens CD, Barnhart KT, Bradley LD, Feinberg E, Gillispie V, Hurtado S, Kim JH, Wang A, Wang H, Stewart EA. Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis. F S Rep. 2021 May 26;2(3):338-346. doi: 10.1016/j.xfre.2021.05.004. eCollection 2021 Sep.
• Beck D, Winzenborg I, Gao W, Mostafa NM, Noertersheuser P, Chiuve SE, Owens C, Shebley M. Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women. Clin Transl Sci. 2021 Jul;14(4):1452-1463. doi: 10.1111/cts.13006. Epub 2021 Apr 8. Erratum In: Clin Transl Sci. 2022 Mar;15(3):799.
• Al-Hendy A, Bradley L, Owens CD, Wang H, Barnhart KT, Feinberg E, Schlaff WD, Puscheck EE, Wang A, Gillispie V, Hurtado S, Muneyyirci-Delale O, Archer DF, Carr BR, Simon JA, Stewart EA. Predictors of response for elagolix with add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids. Am J Obstet Gynecol. 2021 Jan;224(1):72.e1-72.e50. doi: 10.1016/j.ajog.2020.07.032. Epub 2020 Jul 20.
• Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Feinberg EC, Hurtado SM, Kim J, Liu R, Mabey RG Jr, Owens CD, Poindexter A, Puscheck EE, Rodriguez-Ginorio H, Simon JA, Soliman AM, Stewart EA, Watts NB, Muneyyirci-Delale O. Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids. N Engl J Med. 2020 Jan 23;382(4):328-340. doi: 10.1056/NEJMoa1904351.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): January 18, 2018
• Study Completion (Actual): December 12, 2018

Study Registration Dates

• First Submitted: January 8, 2016
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (Estimate): January 13, 2016

Study Record Updates

• Last Update Posted (Actual): June 29, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Elagolix; ABT-620; Menorrhagia; HMB; Heavy Menstrual Bleeding; Elagolix Sodium; Heavy Uterine Bleeding; Leiomyomata; Elagolix + E2/NETA; Elagolix + Norethindrone Acetate
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Uterine Diseases; Connective Tissue Diseases; Neoplasms, Connective Tissue; Menstruation Disturbances; Neoplasms, Muscle Tissue; Uterine Hemorrhage; Hemorrhage; Leiomyoma; Myofibroma; Menorrhagia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Norethindrone; Norethindrone Acetate
• Other Study ID Numbers: M12-815

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No