An Extension Study to Evaluate the Efficacy and Safety of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Extension Study to Evaluate the Efficacy and Safety of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

This is an extension study for women who have already received six months of treatment in the phase III clinical trial M12-815 (NCT02654054) or M12-817 (NCT02691494), and will evaluate the long-term efficacy and safety of elagolix administered alone and in combination with estradiol/norethindrone acetate for an additional six months in the treatment of heavy menstrual bleeding associated with uterine fibroids.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 433
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Windsor, Ontario, Canada, N8W 5R7
      • Victory Reproductive Care /ID# 153299
• Puerto Rico
  • San Juan, Puerto Rico, 00917
    • Rodriguez-Ginorio, San Juan /ID# 153328
  • San Juan, Puerto Rico, 00935
    • School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 153329
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235-3430
      • Alabama Clinical Therapeutics, LLC /ID# 153217
    • Birmingham, Alabama, United States, 35235-3430
      • Alabama Clinical Therapeutics, LLC /ID# 153336
    • Dothan, Alabama, United States, 36303
      • Choice Research, LLC /ID# 153492
    • Fairhope, Alabama, United States, 36532
      • Brown, Pearson, Guepet Gynecology /ID# 153278
    • Mobile, Alabama, United States, 36604-3302
      • University of South Alabama /ID# 153415
    • Mobile, Alabama, United States, 36608
      • Mobile, Ob-Gyn, P.C. /ID# 153442
  • Arizona
    • Mesa, Arizona, United States, 85209
      • Mesa Obstetricians and Gynecol /ID# 153269
  • California
    • Cerritos, California, United States, 90703
      • Core Healthcare Group /ID# 153282
    • Encinitas, California, United States, 92024
      • Diagnamics Inc. /ID# 153347
    • La Mesa, California, United States, 91942
      • Grossmont Ctr Clin Research /ID# 153324
    • Norwalk, California, United States, 90650
      • Futura Research, Inc. /ID# 153345
    • San Fernando, California, United States, 91340
      • Farid Yasharpour MD Medical Co /ID# 153482
  • Colorado
    • Greenwood Village, Colorado, United States, 80111
      • Advanced Women's Health Institution /ID# 153401
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Health Research Institute /ID# 153321
    • Washington, District of Columbia, United States, 20011
      • Emerson Clinical Research Inst /ID# 162755
    • Washington, District of Columbia, United States, 20036
      • James A. Simon, MD, PC /ID# 153323
  • Florida
    • Boynton Beach, Florida, United States, 33436-6634
      • Helix Biomedics, LLC /ID# 153440
    • Brandon, Florida, United States, 33510-3107
      • Brandon Premier Health Care, PA /ID# 165791
    • Clearwater, Florida, United States, 33759
      • Florida Fertility Institute /ID# 153308
    • DeBary, Florida, United States, 32713-2260
      • Omega Research Consultants, LLC /ID# 153381
    • Fort Lauderdale, Florida, United States, 33316
      • KO Clinical Research, LLC /ID# 153198
    • Fort Myers, Florida, United States, 33916
      • Clinical Physiology Assoc. /ID# 153444
    • Jacksonville, Florida, United States, 32256
      • Solutions Through Adv Rch /ID# 153283
    • Kenneth City, Florida, United States, 33709-3113
      • Meridien Research /ID# 153310
    • Lake Worth, Florida, United States, 33461
      • Altus Research, Inc /ID# 153307
    • Margate, Florida, United States, 33063
      • South Florida Wellness & Clinic /ID# 153420
    • Miami, Florida, United States, 33126
      • LCC Medical Research Institute /ID# 153296
    • Miami, Florida, United States, 33144
      • Invictus Clinical Research Group,LLC /ID# 153196
    • Miami, Florida, United States, 33161
      • Healthcare Clinical Data, Inc /ID# 153425
    • Miami, Florida, United States, 33166
      • Ocean Blue Med Research Ctr /ID# 153225
    • Miami Lakes, Florida, United States, 33016-1501
      • Precision Research Org, LLC /ID# 153276
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research /ID# 153206
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute /ID# 153413
    • Orlando, Florida, United States, 32806
      • Clinical Associates of Orlando /ID# 153427
    • Panama City, Florida, United States, 32045
      • Unified Womens Clin Research /ID# 153229
    • Plantation, Florida, United States, 33324
      • All Wmns HC of West Broward /ID# 153434
    • Saint Cloud, Florida, United States, 34769
      • Oncova Clinical Research, Inc. /ID# 153497
    • Sarasota, Florida, United States, 34239
      • Physician Care Clin. Res., LLC /ID# 153210
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc /Id# 153456
    • Tampa, Florida, United States, 33612
      • University of South Florida /ID# 153271
    • Wellington, Florida, United States, 33414
      • Axcess Medical Research /ID# 153500
    • Wellington, Florida, United States, 33414
      • Virtus Research Consultant,LLC /ID# 153398
    • West Palm Beach, Florida, United States, 33409
      • Comprehensive Clinical Trials /ID# 153350
  • Georgia
    • Alpharetta, Georgia, United States, 30005-4419
      • Atlanta Medical Research Insti /ID# 153298
    • Alpharetta, Georgia, United States, 30005
      • Paramount Research Solutions /ID# 153424
    • Alpharetta, Georgia, United States, 30005
      • Paramount Research Solutions /ID# 160974
    • Atlanta, Georgia, United States, 30328
      • Mount Vernon Clinical Res, LLC /ID# 153403
    • Atlanta, Georgia, United States, 30342
      • Atlanta Women's Research Inst /ID# 153212
    • Augusta, Georgia, United States, 30909
      • Masters of Clinical Research, Inc. /ID# 153295
    • College Park, Georgia, United States, 30349
      • Paramount Research Solutions /ID# 153351
    • Savannah, Georgia, United States, 31406
      • Fellows Research Alliance, Inc /ID# 153227
    • Suwanee, Georgia, United States, 30024-6988
      • Clinical Research Consultants of Atlanta /ID# 153285
    • Suwanee, Georgia, United States, 30024-7159
      • Atlanta Gynecology Research Institute /ID# 200074
  • Idaho
    • Meridian, Idaho, United States, 83646-1144
      • Sonora Clinical Research /ID# 153231
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • Affinity Clinical Research /ID# 153417
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • Bluegrass Clinical Research /ID# 153280
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Clinical Trials Management, LLC - Covington /ID# 153211
    • Covington, Louisiana, United States, 70433
      • Clinical Trials Management, LLC - Covington /ID# 153439
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Baptist Medical Center /ID# 153459
    • Shreveport, Louisiana, United States, 71118
      • Omni Fertility and Laser Insti /ID# 153228
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Baltimore Suburban Health /ID# 168386
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720-2972
      • NECCR Fall River LLC /ID# 153274
    • Fall River, Massachusetts, United States, 02720
      • Genesis Clinical Research /ID# 153379
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group,Inc /ID# 153302
    • Saginaw, Michigan, United States, 48604
      • Saginaw Valley Med Res Group /ID# 153498
    • Southfield, Michigan, United States, 48034
      • Wayne State University Physician Group - Southfield /ID# 153418
  • Nevada
    • Las Vegas, Nevada, United States, 89106-4017
      • Accent Clinical Trials /ID# 153474
    • Las Vegas, Nevada, United States, 89113
      • Office of Edmond E. Pack, MD /ID# 153411
    • Las Vegas, Nevada, United States, 89128
      • Mabey, Las Vegas, NV /ID# 153314
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrence OB/GYN /ID# 153218
    • Neptune, New Jersey, United States, 07753-4859
      • Jersey Shore University Medical Center /ID# 153495
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Bosque Women's Care /ID# 153223
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center /ID# 153344
    • New York, New York, United States, 10016-6023
      • Manhattan Medical Research /ID# 153386
    • New York, New York, United States, 10032-3725
      • Weill Cornell Medicine /ID# 153275
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Cwrwc /Id# 153313
    • Greensboro, North Carolina, United States, 27408
      • Unified Women's Clinical Research-Greensboro /ID# 153499
    • High Point, North Carolina, United States, 27262
      • Pinewest Ob-Gyn, Inc. /ID# 153197
    • New Bern, North Carolina, United States, 28562
      • Eastern Carolina Women's Centr /ID# 153341
    • Raleigh, North Carolina, United States, 27607
      • Unified Women's Clinical Resea /ID# 153312
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC /ID# 153402
    • Winston-Salem, North Carolina, United States, 27103
      • Unified Women's Clinical Resea /ID# 153297
  • Ohio
    • Beavercreek, Ohio, United States, 45432
      • Clinical Inquest Center Ltd /ID# 153436
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center /ID# 153201
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland /ID# 153450
    • Toledo, Ohio, United States, 43614
      • University of Toledo /ID# 153409
    • Westerville, Ohio, United States, 43081
      • Comprehensive Womens Care /ID# 153396
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Medical Group-Portland /ID# 168286
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Main Line Fertility Center /ID# 153410
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University and Milton S. Hershey Medical Center /ID# 153443
    • Philadelphia, Pennsylvania, United States, 19104-5502
      • University of Pennsylvania /ID# 153203
    • Philadelphia, Pennsylvania, United States, 19107-4414
      • Thomas Jefferson University /ID# 153319
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research of Philadelphia, LLC /ID# 153279
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hosp Clncl Trials Ofc /ID# 153475
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina /ID# 153325
    • Columbia, South Carolina, United States, 29201
      • Vista Clinical Research /ID# 153399
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Medical Research /ID# 153405
    • Chattanooga, Tennessee, United States, 37421-1605
      • WR-ClinSearch /ID# 153404
    • Memphis, Tennessee, United States, 38119-3895
      • Research Memphis Associates, LLC /ID# 153322
    • Menphis, Tennessee, United States, 38104
      • Women's Health Trials /ID# 153426
    • Nashville, Tennessee, United States, 37203
      • Access Clinical Trials, Inc. /ID# 153441
  • Texas
    • Austin, Texas, United States, 78703-1448
      • Lotus Gynecology /ID# 153476
    • Dallas, Texas, United States, 75231
      • Texas Health Presbyterian Hosp /ID# 153339
    • Dallas, Texas, United States, 75390-7208
      • UT Southwestern Medical Center /ID# 153400
    • Fort Worth, Texas, United States, 76104-4110
      • Baylor Scott & White /ID# 153273
    • Frisco, Texas, United States, 75035
      • Willowbend Health and Wellness /ID# 153458
    • Houston, Texas, United States, 77030
      • Advances in Health, Inc. /ID# 153414
    • Houston, Texas, United States, 77054
      • The Woman's Hospital of Texas /ID# 153270
    • Lampasas, Texas, United States, 76550
      • FMC Science /ID# 153289
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas,Inc. /ID# 153209
    • San Antonio, Texas, United States, 78258
      • Discovery Clinical Trials-San Antonio /ID# 153315
    • Sugar Land, Texas, United States, 77479
      • Houston Ctr for Clin Research /ID# 153221
    • Webster, Texas, United States, 77598
      • Center of Reproductive Medicin /ID# 153320
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Tidewater Physicians for Women /ID# 153432
    • Norfolk, Virginia, United States, 23507-1627
      • Eastern Virginia Med School /ID# 153380
    • North Chesterfield, Virginia, United States, 23235-4722
      • Clinical Research Partners, LL /ID# 153412
    • Richmond, Virginia, United States, 23220-4459
      • Clinical Research Partners, LLC /ID# 153343
    • Richmond, Virginia, United States, 23225
      • Clinical Trials Virginia, Inc. /ID# 153419
    • Vienna, Virginia, United States, 22182
      • Emerson Clinical Research Inst /ID# 153416
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center /ID# 153342
    • Seattle, Washington, United States, 98105
      • Seattle Women's Health, Research, Gynecology /ID# 153306

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:

• Participant has completed the 6-Month Treatment Period of their respective Pivotal Study (either Study M12-815 or Study M12-817).
• Participant did not meet removal criteria in bone mineral density (BMD) decrease in the spine, total hip and femoral neck at Month 6 of the Treatment Period of their respective Pivotal Study
• Participant has negative urine and/or serum pregnancy test(s) results were consistently negative during the Treatment Period of their respective Pivotal Study and prior to first dose in this study.
• Participant's endometrial biopsy from the Month 6 Visit of their respective Pivotal Study shows no clinically significant endometrial pathology.

Exclusion Criteria:

• Participant met criteria for removal from therapy in her respective Pivotal Study.
• Participant is planning a pregnancy within the next 18 months.
• Participant has current suicidal markers as noted at the Month 6 visit of her respective pivotal study.
• Participant has any new medical conditions that may be unsuitable for participation.
• Participant is using any systemic corticosteroids for over 14 days 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Elagolix plus Estradiol/Norethindrone Acetate (E2/NETA); Elagolix 300 mg twice daily (BID) and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) once daily (QD)	Drug: Estradiol/Norethindrone Acetate; capsules; Drug: Elagolix; film-coated tablets; Other Names: ABT-620; elagolix sodium
EXPERIMENTAL: Elagolix; Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD	Drug: Elagolix; film-coated tablets; Other Names: ABT-620; elagolix sodium

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 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.	From Month 0 (Baseline in Pivotal Study) to Final Month of Treatment Period (up through Month 6 in Extension Study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period	Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, 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 in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through Month 6)
Percent Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period	Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, 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 in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through 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.	Final Month of Treatment Period (up through Month 6)
Percentage of Participants With Baseline Hemoglobin Concentration ≤ 10.5 g/dL and an Increase From Baseline > 2 g/dL at Month 6 During the Treatment Period		Month 6

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Simon JA, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Dayspring T, Feinberg EC, Gillispie V, Hurtado S, Kim J, Liu R, Owens CD, Muneyyirci-Delale O, Wang A, Watts NB, Schlaff WD. Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas. Obstet Gynecol. 2020 Jun;135(6):1313-1326. doi: 10.1097/AOG.0000000000003869.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 14, 2016
• Primary Completion (ACTUAL): May 7, 2018
• Study Completion (ACTUAL): March 22, 2019

Study Registration Dates

• First Submitted: September 24, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (ESTIMATE): October 6, 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; Uterine Fibroids; Heavy Menstrual Bleeding; Elagolix Sodium; Elagolix plus 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; Norethindrone; Norethindrone Acetate
• Other Study ID Numbers: M12-816

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