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

NCT02654054 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: M12-815
• Study Type: interventional
• Target: 413
• Locations: 3 countries
• Sites: 96

Brief Summary

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.

Conditions

Uterine Fibroids; Heavy Menstrual Bleeding

Keywords

Elagolix; Elagolix Sodium; Heavy Uterine Bleeding; Heavy Menstrual Bleeding; Leiomyomata; Menorrhagia; ABT-620; Elagolix + E2/NETA; Elagolix + Norethindrone Acetate; HMB

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change From Baseline in MBL Volume to the Final Month

  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

  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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo for both elagolix twice daily (BID) and norethindrone acetate (E2/NETA) once daily (QD)

Drug: Placebo for Estradiol/Norethindrone Acetate; Drug: Placebo for Elagolix

Elagolix

EXPERIMENTAL

Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD

Drug: Elagolix; Drug: Placebo for Estradiol/Norethindrone Acetate

Elagolix + E2/NETA

EXPERIMENTAL

Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD

Drug: Elagolix; Drug: Estradiol/Norethindrone Acetate

Interventions

Elagolix DRUG

Film-coated tablets

Also known as: ABT-620, elagolix sodium

Elagolix; Elagolix + E2/NETA

Placebo for Estradiol/Norethindrone Acetate DRUG

Placebo capsules

Elagolix; Placebo

Estradiol/Norethindrone Acetate DRUG

Commercially-available E2/NETA tablets were over-encapsulated to maintain study blinding.

Also known as: E2/NETA

Elagolix + E2/NETA

Placebo for Elagolix DRUG

Film-coated placebo tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 51 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (96)

Summers, Birmingham, AL /ID# 139684

Birmingham, Alabama, 35235, United States

Location

University of South Alabama /ID# 148763

Mobile, Alabama, 36604-3302, United States

Location

WCCT Global, LLC /ID# 145666

Costa Mesa, California, 92626, United States

Location

American Clinical Trials /ID# 147374

Hawaiian Gardens, California, 90716, United States

Location

Grossmont Ctr Clin Research /ID# 144011

La Mesa, California, 91942, United States

Location

Long Beach Clinical Trial Serv /ID# 152424

Long Beach, California, 90806, United States

Location

National Research Institute /ID# 151629

Los Angeles, California, 90057, United States

Location

University of California, Los Angeles /ID# 144107

Los Angeles, California, 90095, United States

Location

Beach OBGYN Medical Group /ID# 151414

Newport Beach, California, 92663-3657, United States

Location

Advanced RX Clinical Research /ID# 149168

Westminster, California, 92683-4567, United States

Location

Bluebird Clinical Trials, LLC /ID# 144843

Colorado Springs, Colorado, 80923, United States

Location

Advanced Women's Health Institution /ID# 144108

Greenwood Village, Colorado, 80111, United States

Location

Medstar Health Research Institute /ID# 145933

Washington D.C., District of Columbia, 20010, United States

Location

James A. Simon, MD, PC /ID# 139675

Washington D.C., District of Columbia, 20036, United States

Location

Helix Biomedics, LLC /ID# 147114

Boynton Beach, Florida, 33436-6634, United States

Location

Brandon Premier Health Care, PA /ID# 153130

Brandon, Florida, 33510-3107, United States

Location

Florida Clin Res Group /ID# 139811

Ckearwater, Florida, 33759, United States

Location

Universal Clinical Research A /ID# 139742

Doral, Florida, 33166, United States

Location

Clinical Physiology Associates /ID# 139736

Fort Myers, Florida, 33912, United States

Location

Meridien Research /ID# 139663

Kenneth City, Florida, 33709-3113, United States

Location

Altus Research, Inc /ID# 139662

Lake Worth, Florida, 33461, United States

Location

South Florida Wellness & Clinic /ID# 143558

Margate, Florida, 33063, United States

Location

LCC Medical Research Institute /ID# 143551

Miami, Florida, 33126, United States

Location

Healthcare Clinical Data, Inc /ID# 139650

Miami, Florida, 33161, United States

Location

Ocean Blue Med Research Ctr /ID# 139826

Miami, Florida, 33166, United States

Location

Salom Tangir, LLC /ID# 151732

Miramar, Florida, 33027, United States

Location

Advanced Research Institute /ID# 143554

New Port Richey, Florida, 34653, United States

Location

Clinical Associates of Orlando /ID# 148123

Orlando, Florida, 32806, United States

Location

Omega Research Consultants /ID# 139648

Orlando, Florida, 32810, United States

Location

Unified Womens Clin Research /ID# 145169

Panama City, Florida, 32045, United States

Location

Comprehensive Clinical Trials /ID# 139644

West Palm Beach, Florida, 33409, United States

Location

Atlanta Medical Research Insti /ID# 147117

Alpharetta, Georgia, 30005-4419, United States

Location

Paramount Research Solutions /ID# 139645

Alpharetta, Georgia, 30005, United States

Location

Agile Clinical Research Trials /ID# 143563

Atlanta, Georgia, 30328, United States

Location

Perimeter Inst Clinical Resear /ID# 148298

Atlanta, Georgia, 30338, United States

Location

Masters of Clinical Research, Inc. /ID# 139658

Augusta, Georgia, 30909, United States

Location

Fellows Research Alliance, Inc /ID# 139655

Savannah, Georgia, 31406, United States

Location

Boise Family Medical Center /ID# 139844

Boise, Idaho, 83709, United States

Location

Women's Health Practice, LLC /ID# 143569

Champaign, Illinois, 61820, United States

Location

Great Lakes Clinical Trials /ID# 148135

Chicago, Illinois, 60640, United States

Location

Affinity Clinical Research /ID# 150980

Oak Brook, Illinois, 60523, United States

Location

American Health Network of IN /ID# 139822

Avon, Indiana, 46123, United States

Location

GTC Research /ID# 141854

Kansas City, Kansas, 66218, United States

Location

Cypress Medical Research Ctr /ID# 147116

Wichita, Kansas, 67226, United States

Location

Research Integrity, LLC /ID# 139727

Owensboro, Kentucky, 42303-1089, United States

Location

Clinical Trials Management, LLC - Covington /ID# 139651

Covington, Louisiana, 70433, United States

Location

Ochsner Baptist Medical Center /ID# 139740

New Orleans, Louisiana, 70115, United States

Location

Omni Fertility and Laser Insti /ID# 139836

Shreveport, Louisiana, 71118, United States

Location

Capital Women's Care /ID# 144109

Frederick, Maryland, 21708, United States

Location

Genesis Clinical Research - Fall River /ID# 148449

Fall River, Massachusetts, 02723, United States

Location

Great Lakes Research Group,Inc /ID# 139659

Bay City, Michigan, 48706, United States

Location

Grand Rapids Womens Health /ID# 139705

Grand Rapids, Michigan, 49503, United States

Location

Wayne State University Physician Group - Southfield /ID# 139802

Southfield, Michigan, 48034, United States

Location

Office of Edmond E. Pack, MD /ID# 139792

Las Vegas, Nevada, 89113, United States

Location

Mabey, Las Vegas, NV /ID# 148138

Las Vegas, Nevada, 89128, United States

Location

Lawrence OB/GYN /ID# 143567

Lawrenceville, New Jersey, 08648, United States

Location

Bosque Women's Care /ID# 145934

Albuquerque, New Mexico, 87109, United States

Location

Manhattan Medical Research /ID# 144471

New York, New York, 10016-6023, United States

Location

Cwrwc /Id# 139664

Durham, North Carolina, 27713, United States

Location

Unified Women's Clinical Research-Greensboro /ID# 139829

Greensboro, North Carolina, 27408, United States

Location

Unified Women's Clinical Resea /ID# 139774

Raleigh, North Carolina, 27607, United States

Location

PMG Research of Wilmington LLC /ID# 152563

Wilmington, North Carolina, 28401, United States

Location

Unified Women's Clinical Resea /ID# 144721

Winston-Salem, North Carolina, 27103, United States

Location

University of Cincinnati /ID# 139820

Cincinnati, Ohio, 45267-0585, United States

Location

Univ Hosp Cleveland /ID# 139741

Cleveland, Ohio, 44106, United States

Location

Complete Healthcare for Women /ID# 139673

Columbus, Ohio, 43231, United States

Location

Miami Valley Hospital /ID# 144430

Dayton, Ohio, 45409, United States

Location

University of Toledo /ID# 139787

Toledo, Ohio, 43614, United States

Location

Legacy Medical Group-Portland /ID# 148807

Portland, Oregon, 97210, United States

Location

Main Line Fertility Center /ID# 150295

Bryn Mawr, Pennsylvania, 19010, United States

Location

Penn State University and Milton S. Hershey Medical Center /ID# 139733

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University /ID# 139812

Philadelphia, Pennsylvania, 19107-4414, United States

Location

Temple University Hospital /ID# 151429

Philadelphia, Pennsylvania, 19140, United States

Location

Clinical Trials Research Svcs /ID# 139707

Pittsburgh, Pennsylvania, 15206, United States

Location

Medical University of South Carolina /ID# 148754

Charleston, South Carolina, 29425, United States

Location

Vista Clinical Research /ID# 139797

Columbia, South Carolina, 29201, United States

Location

WR-ClinSearch /ID# 143538

Chattanooga, Tennessee, 37421-1605, United States

Location

Research Memphis Associates, LLC /ID# 139674

Memphis, Tennessee, 38119-3895, United States

Location

Access Clinical Trials, Inc. /ID# 139730

Nashville, Tennessee, 37203, United States

Location

UT Southwestern Medical Center /ID# 143537

Dallas, Texas, 75390-7208, United States

Location

Advances in Health, Inc. /ID# 139672

Houston, Texas, 77030, United States

Location

Victorium Clinical Research /ID# 149630

San Antonio, Texas, 78230, United States

Location

Discovery Clinical Trials-San Antonio /ID# 139776

San Antonio, Texas, 78258, United States

Location

Houston Ctr for Clin Research /ID# 149149

Sugar Land, Texas, 77479, United States

Location

Center of Reproductive Medicin /ID# 139813

Webster, Texas, 77598, United States

Location

Eastern Virginia Med School /ID# 139647

Norfolk, Virginia, 23507-1627, United States

Location

Clinical Research Partners, LL /ID# 143999

North Chesterfield, Virginia, 23235-4722, United States

Location

Clinical Trials Virginia, Inc. /ID# 139801

Richmond, Virginia, 23225, United States

Location

Emerson Clinical Research /ID# 147373

Vienna, Virginia, 22182, United States

Location

Seattle Women's Health, Research, Gynecology /ID# 139768

Seattle, Washington, 98105, United States

Location

Premier Clinical Research /ID# 148145

Spokane, Washington, 99202, United States

Location

Froedtert and Medical College /ID# 143566

Milwaukee, Wisconsin, 53226-3522, United States

Location

IWK Health Center /ID# 149066

Halifax, Nova Scotia, B3K 6R8, Canada

Location

The Ottawa Hospital /ID# 148695

Ottawa, Ontario, K1H 8L6, Canada

Location

Rodriguez-Ginorio, San Juan /ID# 139847

San Juan, 00917, Puerto Rico

Location

School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 139848

San Juan, 00935, Puerto Rico

Location

Related Publications (7)

• Simon JA, Stewart EA, Jewell S, Li M, Snabes MC. Impact of demographic and clinical factors on elagolix plus add-back therapy effects on patient-reported nonbleeding symptoms in women with heavy menstrual bleeding and uterine fibroids: a post hoc analysis of data from two clinical trials. F S Rep. 2024 Jun 14;5(3):285-295. doi: 10.1016/j.xfre.2024.06.002. eCollection 2024 Sep.

  PMID: 39381651 DERIVED

• 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.

  PMID: 34878624 DERIVED

• 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.

  PMID: 34582715 DERIVED

• 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.

  PMID: 34553161 DERIVED

• 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.

  PMID: 33650259 DERIVED

• 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.

  PMID: 32702363 DERIVED

• 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.

  PMID: 31971678 DERIVED

MeSH Terms

Conditions

Leiomyoma; Menorrhagia

Interventions

elagolix; Estradiol; Norethindrone Acetate; estradiol, norethindrone drug combination

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances

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

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: January 8, 2016
• First Posted: January 13, 2016
• Study Start: December 22, 2015
• Primary Completion: January 18, 2018
• Study Completion: December 12, 2018
• Last Updated: June 29, 2020
• Results First Posted: June 29, 2020

Record last verified: 2020-06

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

CA (2); PR (2); US (92)