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 (Replicate Study)

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): 378
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Sudbury, Ontario, Canada, P3A 1W8
      • Medicor Research Inc. /ID# 153406
    • Windsor, Ontario, Canada, N8W 5R7
      • Victory Reproductive Care /ID# 150247
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235-3430
      • Alabama Clinical Therapeutics, LLC /ID# 152258
    • Dothan, Alabama, United States, 36303
      • Choice Research, LLC /ID# 150988
    • Fairhope, Alabama, United States, 36532
      • Brown, Pearson, Guepet Gynecology /ID# 151020
    • Mobile, Alabama, United States, 36608
      • Mobile, Ob-Gyn, P.C. /ID# 144294
  • Arizona
    • Mesa, Arizona, United States, 85209
      • Mesa Obstetricians and Gynecol /ID# 149139
    • Tucson, Arizona, United States, 85712
      • Visions Clinical Research-Tucs /ID# 151017
  • California
    • Cerritos, California, United States, 90703
      • Core Healthcare Group /ID# 151016
    • Encinitas, California, United States, 92024
      • Diagnamics Inc. /ID# 152469
    • Huntington Beach, California, United States, 92646
      • HCP Clinical Research LLC /ID# 154434
    • Laguna Hills, California, United States, 92653-3621
      • Alliance Research Centers /ID# 149752
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles /ID# 149760
    • Norwalk, California, United States, 90650
      • Futura Research, Inc. /ID# 149759
    • San Fernando, California, United States, 91340
      • Farid Yasharpour MD Medical Co /ID# 149770
    • Tustin, California, United States, 92780
      • Clinical Trial Investigators /ID# 152470
    • Valley Village, California, United States, 91607
      • Bayview Research Group LLC /ID# 153799
  • District of Columbia
    • Washington, District of Columbia, United States, 20011
      • Emerson Clinical Research Inst /ID# 152348
  • Florida
    • Aventura, Florida, United States, 33180
      • Ideal Clinical Research Inc. /ID# 149757
    • Brandon, Florida, United States, 33510
      • Seffner Premier Health Care, P /ID# 167480
    • Clearwater, Florida, United States, 33756
      • Olympian Clinical Research /ID# 149756
    • Fort Lauderdale, Florida, United States, 33316
      • KO Clinical Research, LLC /ID# 144299
    • Gainesville, Florida, United States, 32610
      • University of Florida /ID# 149751
    • Jacksonville, Florida, United States, 32256
      • Solutions Through Adv Rch /ID# 151021
    • Kenneth City, Florida, United States, 33709-3113
      • Meridien Research /ID# 167100
    • Miami, Florida, United States, 33144
      • Invictus Clinical Research Group,LLC /ID# 141859
    • Miami Lakes, Florida, United States, 33016-1501
      • Precision Research Org, LLC /ID# 144335
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research /ID# 149765
    • Plantation, Florida, United States, 33324
      • All Wmns HC of West Broward /ID# 144298
    • Saint Cloud, Florida, United States, 34769
      • Oncova Clinical Research, Inc. /ID# 149764
    • Sarasota, Florida, United States, 34239
      • Physician Care Clin. Res., LLC /ID# 149766
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc /Id# 144325
    • Stuart, Florida, United States, 34994
      • Martin Health System Center /ID# 152263
    • Tampa, Florida, United States, 33612
      • University of South Florida /ID# 149754
    • Wellington, Florida, United States, 33414
      • Axcess Medical Research /ID# 149769
    • Wellington, Florida, United States, 33414
      • Virtus Research Consultant,LLC /ID# 144296
  • Georgia
    • Alpharetta, Georgia, United States, 30005
      • Paramount Research Solutions /ID# 149291
    • Atlanta, Georgia, United States, 30328
      • Agile Clinical Research Trials /ID# 167074
    • Atlanta, Georgia, United States, 30328
      • Mount Vernon Clinical Res, LLC /ID# 144297
    • Atlanta, Georgia, United States, 30342
      • Atlanta Women's Research Inst /ID# 144303
    • Augusta, Georgia, United States, 30909
      • Masters of Clinical Research, Inc. /ID# 167400
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University /ID# 144295
    • Savannah, Georgia, United States, 31406-2675
      • Meridian Clinical Research, LLC /ID# 149144
    • Smyrna, Georgia, United States, 30080
      • Gyn-Care, Inc. /ID# 149341
    • Suwanee, Georgia, United States, 30024-7159
      • Atlanta Gynecology Research Institute /ID# 151014
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Womens Healthcare Assoc, DBA /ID# 149762
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research /ID# 149767
  • Illinois
    • Chicago, Illinois, United States, 60637-1443
      • University of Chicago /ID# 152257
    • Oak Brook, Illinois, United States, 60523
      • Affinity Clinical Research /ID# 167119
    • Palos Heights, Illinois, United States, 60463-1440
      • Center for Women's Research, Inc /ID# 144300
  • Indiana
    • Fort Wayne, Indiana, United States, 46825
      • Women's Health Advantage /ID# 144301
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic /ID# 150105
  • Kansas
    • Wichita, Kansas, United States, 67205
      • PRN Professional Research Network of Kansas, LLC /ID# 152265
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • Bluegrass Clinical Research /ID# 150103
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Clinical Trials Management, LLC - Covington /ID# 144314
    • New Orleans, Louisiana, United States, 70125-1923
      • Women Under Study, LLC /ID# 144312
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Baltimore Suburban Health /ID# 154638
    • Glen Burnie, Maryland, United States, 21063
      • Womens Health Center /ID# 154209
    • Lutherville, Maryland, United States, 21093
      • Maryland Ctr for Sexual Health /ID# 149778
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720-2972
      • NECCR Fall River LLC /ID# 149584
  • Michigan
    • Saginaw, Michigan, United States, 48604
      • Saginaw Valley Med Res Group /ID# 149768
  • Nevada
    • Las Vegas, Nevada, United States, 89106-4017
      • Accent Clinical Trials /ID# 149753
  • New Jersey
    • Neptune, New Jersey, United States, 07753-4859
      • Jersey Shore University Medical Center /ID# 149779
    • Stratford, New Jersey, United States, 08084
      • Rowan University SOM /ID# 152697
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center /ID# 149582
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center /ID# 144311
    • New York, New York, United States, 10016-6023
      • Manhattan Medical Research /ID# 167077
    • New York, New York, United States, 10032-3725
      • Weill Cornell Medicine /ID# 149585
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Duplicate_Unified Women's Clinical Research-Fayetteville /ID# 149587
    • Greensboro, North Carolina, United States, 27408
      • Unified Women's Clinical Research-Greensboro /ID# 149588
    • High Point, North Carolina, United States, 27262
      • Pinewest Ob-Gyn, Inc. /ID# 145671
    • New Bern, North Carolina, United States, 28562
      • Eastern Carolina Women's Centr /ID# 144309
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC /ID# 144307
  • Ohio
    • Beavercreek, Ohio, United States, 45432
      • Clinical Inquest Center Ltd /ID# 148728
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center /ID# 149761
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital /ID# 150104
    • Dayton, Ohio, United States, 45417
      • Alpha Research Associates LLC /ID# 152471
    • Westerville, Ohio, United States, 43081
      • Comprehensive Womens Care /ID# 144306
  • Pennsylvania
    • Levittown, Pennsylvania, United States, 19056
      • Family Medical Associates /ID# 145668
    • Philadelphia, Pennsylvania, United States, 19104-5502
      • University of Pennsylvania /ID# 149586
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research of Philadelphia, LLC /ID# 151015
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hosp Clncl Trials Ofc /ID# 149583
  • Tennessee
    • Bristol, Tennessee, United States, 37620-7346
      • Holston Medical Group /ID# 149763
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Medical Research /ID# 145667
    • Hixson, Tennessee, United States, 37343-3992
      • Chattanooga Women for Women /ID# 167051
    • Jackson, Tennessee, United States, 38305
      • The Jackson Clinic, PA /ID# 145670
    • Memphis, Tennessee, United States, 38104
      • The Womens Physician Group /ID# 144317
    • Nashville, Tennessee, United States, 37203
      • Access Clinical Trials, Inc. /ID# 167333
  • Texas
    • Austin, Texas, United States, 78703-1448
      • Lotus Gynecology /ID# 149140
    • Baytown, Texas, United States, 77521-2415
      • Inquest Clinical Research /ID# 149755
    • Dallas, Texas, United States, 75231
      • Texas Health Presbyterian Hosp /ID# 149142
    • Houston, Texas, United States, 77030-3411
      • Baylor College of Medicine /ID# 149141
    • Houston, Texas, United States, 77054
      • The Woman's Hospital of Texas /ID# 144319
    • Houston, Texas, United States, 77058
      • Centex Studies, Inc. - Houston /ID# 150106
    • Houston, Texas, United States, 77084
      • BI Research Center /ID# 149143
    • Lampasas, Texas, United States, 76550
      • FMC Science /ID# 151802
    • Plano, Texas, United States, 75035
      • Willowbend Health and Wellness /ID# 144318
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas,Inc. /ID# 144322
    • Webster, Texas, United States, 77598
      • Center of Reproductive Medicin /ID# 167235
  • Virginia
    • Franklin, Virginia, United States, 23851
      • Southampton Women's Health /ID# 152325
    • Norfolk, Virginia, United States, 23502
      • Tidewater Physicians for Women /ID# 144321
    • Richmond, Virginia, United States, 23220-4459
      • Clinical Research Partners, LLC /ID# 144310
    • Richmond, Virginia, United States, 23226-1930
      • Alliance Womens Health /ID# 152468
  • Washington
    • Richland, Washington, United States, 99352
      • Zain Research /ID# 151018
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center /ID# 149758

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 51 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
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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 + 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
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
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 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.	Baseline and 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	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.	Month 0 (Baseline), Month 6
Change From Baseline in MBL Volume to Month 3	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.	Month 0 (Baseline), Month 3
Change From Baseline in MBL Volume to Month 1	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.	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.
• 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): February 3, 2016
• Primary Completion (ACTUAL): February 14, 2018
• Study Completion (ACTUAL): January 23, 2019

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: February 22, 2016
• First Posted (ESTIMATE): February 25, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2021
• Last Update Submitted That Met QC Criteria: July 9, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Elagolix; ABT-620; Menorrhagia; Heavy menstrual bleeding (HMB); Elagolix Sodium; Leiomyomata; Heavy uterine bleeding; 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: M12-817

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; SAP; ANALYTIC_CODE; CSR

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