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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

Phase 3
Completed
Conditions
Uterine Fibroids
Heavy Menstrual Bleeding
Interventions
Registration Number
NCT02654054
Lead Sponsor
AbbVie
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
413
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ElagolixElagolixElagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
PlaceboPlacebo for Estradiol/Norethindrone AcetatePlacebo for both elagolix twice daily (BID) and norethindrone acetate (E2/NETA) once daily (QD)
ElagolixPlacebo for Estradiol/Norethindrone AcetateElagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
Elagolix + E2/NETAEstradiol/Norethindrone AcetateElagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
PlaceboPlacebo for ElagolixPlacebo for both elagolix twice daily (BID) and norethindrone acetate (E2/NETA) once daily (QD)
Elagolix + E2/NETAElagolixElagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Meeting the Criteria for ResponderFinal Month (the last 28 days prior to and including the Reference Day), up to Month 6

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in MBL Volume to the Final MonthMonth 0 (Baseline), Final Month (the last 28 days prior to and including the Reference Day), up 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.

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.

Percentage of Participants With Suppression of Bleeding at the Final MonthFinal Month (the last 28 days prior to and including the Reference Day), up to Month 6

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.

Change From Baseline in MBL Volume to Month 6Month 0 (Baseline), Month 6
Change From Baseline in MBL Volume to Month 3Month 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 6Month 0 (Baseline), Month 6
Change From Baseline in MBL Volume to Month 1Month 0 (Baseline), Month 1

Trial Locations

Locations (96)

Houston Ctr for Clin Research /ID# 149149

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Sugar Land, Texas, United States

Fellows Research Alliance, Inc /ID# 139655

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Savannah, Georgia, United States

University of California, Los Angeles /ID# 144107

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Los Angeles, California, United States

Agile Clinical Research Trials /ID# 143563

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Atlanta, Georgia, United States

Perimeter Inst Clinical Resear /ID# 148298

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Atlanta, Georgia, United States

Great Lakes Clinical Trials /ID# 148135

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Chicago, Illinois, United States

Rodriguez-Ginorio, San Juan /ID# 139847

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San Juan, Puerto Rico

Advances in Health, Inc. /ID# 139672

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Houston, Texas, United States

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

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Seattle, Washington, United States

LCC Medical Research Institute /ID# 143551

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Miami, Florida, United States

Healthcare Clinical Data, Inc /ID# 139650

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Miami, Florida, United States

Ocean Blue Med Research Ctr /ID# 139826

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Miami, Florida, United States

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

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Las Vegas, Nevada, United States

Cwrwc /Id# 139664

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Durham, North Carolina, United States

Access Clinical Trials, Inc. /ID# 139730

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Nashville, Tennessee, United States

Victorium Clinical Research /ID# 149630

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San Antonio, Texas, United States

Discovery Clinical Trials-San Antonio /ID# 139776

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San Antonio, Texas, United States

Summers, Birmingham, AL /ID# 139684

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Birmingham, Alabama, United States

Long Beach Clinical Trial Serv /ID# 152424

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Long Beach, California, United States

Unified Womens Clin Research /ID# 145169

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Panama City, Florida, United States

Cypress Medical Research Ctr /ID# 147116

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Wichita, Kansas, United States

American Health Network of IN /ID# 139822

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Avon, Indiana, United States

Temple University Hospital /ID# 151429

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Philadelphia, Pennsylvania, United States

Center of Reproductive Medicin /ID# 139813

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Webster, Texas, United States

IWK Health Center /ID# 149066

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Halifax, Nova Scotia, Canada

GTC Research /ID# 141854

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Kansas City, Kansas, United States

Legacy Medical Group-Portland /ID# 148807

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Portland, Oregon, United States

Froedtert and Medical College /ID# 143566

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Milwaukee, Wisconsin, United States

PMG Research of Wilmington LLC /ID# 152563

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Wilmington, North Carolina, United States

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

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Greensboro, North Carolina, United States

WCCT Global, LLC /ID# 145666

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Costa Mesa, California, United States

University of South Alabama /ID# 148763

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Mobile, Alabama, United States

American Clinical Trials /ID# 147374

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Hawaiian Gardens, California, United States

Grossmont Ctr Clin Research /ID# 144011

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La Mesa, California, United States

National Research Institute /ID# 151629

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Los Angeles, California, United States

Beach OBGYN Medical Group /ID# 151414

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Newport Beach, California, United States

Bluebird Clinical Trials, LLC /ID# 144843

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Colorado Springs, Colorado, United States

Advanced RX Clinical Research /ID# 149168

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Westminster, California, United States

Medstar Health Research Institute /ID# 145933

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Washington, District of Columbia, United States

Advanced Women's Health Institution /ID# 144108

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Greenwood Village, Colorado, United States

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

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Washington, District of Columbia, United States

Helix Biomedics, LLC /ID# 147114

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Boynton Beach, Florida, United States

Universal Clinical Research A /ID# 139742

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Doral, Florida, United States

Brandon Premier Health Care, PA /ID# 153130

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Brandon, Florida, United States

Florida Clin Res Group /ID# 139811

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Ckearwater, Florida, United States

Clinical Physiology Associates /ID# 139736

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Fort Myers, Florida, United States

Meridien Research /ID# 139663

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Kenneth City, Florida, United States

Altus Research, Inc /ID# 139662

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Lake Worth, Florida, United States

South Florida Wellness & Clinic /ID# 143558

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Margate, Florida, United States

Advanced Research Institute /ID# 143554

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New Port Richey, Florida, United States

Salom Tangir, LLC /ID# 151732

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Miramar, Florida, United States

Paramount Research Solutions /ID# 139645

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Alpharetta, Georgia, United States

Comprehensive Clinical Trials /ID# 139644

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West Palm Beach, Florida, United States

Masters of Clinical Research, Inc. /ID# 139658

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Augusta, Georgia, United States

Women's Health Practice, LLC /ID# 143569

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Champaign, Illinois, United States

Affinity Clinical Research /ID# 150980

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Oak Brook, Illinois, United States

Boise Family Medical Center /ID# 139844

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Boise, Idaho, United States

Research Integrity, LLC /ID# 139727

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Owensboro, Kentucky, United States

Omni Fertility and Laser Insti /ID# 139836

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Shreveport, Louisiana, United States

Clinical Trials Management, LLC - Covington /ID# 139651

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Covington, Louisiana, United States

Capital Women's Care /ID# 144109

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Frederick, Maryland, United States

Great Lakes Research Group,Inc /ID# 139659

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Bay City, Michigan, United States

Genesis Clinical Research - Fall River /ID# 148449

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Fall River, Massachusetts, United States

Wayne State University Physician Group - Southfield /ID# 139802

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Southfield, Michigan, United States

Grand Rapids Womens Health /ID# 139705

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Grand Rapids, Michigan, United States

Lawrence OB/GYN /ID# 143567

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Lawrenceville, New Jersey, United States

Mabey, Las Vegas, NV /ID# 148138

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Las Vegas, Nevada, United States

Bosque Women's Care /ID# 145934

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Albuquerque, New Mexico, United States

Manhattan Medical Research /ID# 144471

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New York, New York, United States

Unified Women's Clinical Resea /ID# 139774

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Raleigh, North Carolina, United States

University of Cincinnati /ID# 139820

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Cincinnati, Ohio, United States

Univ Hosp Cleveland /ID# 139741

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Cleveland, Ohio, United States

Miami Valley Hospital /ID# 144430

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Dayton, Ohio, United States

Complete Healthcare for Women /ID# 139673

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Columbus, Ohio, United States

University of Toledo /ID# 139787

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Toledo, Ohio, United States

Thomas Jefferson University /ID# 139812

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Philadelphia, Pennsylvania, United States

Main Line Fertility Center /ID# 150295

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Bryn Mawr, Pennsylvania, United States

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

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Hershey, Pennsylvania, United States

Vista Clinical Research /ID# 139797

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Columbia, South Carolina, United States

WR-ClinSearch /ID# 143538

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Chattanooga, Tennessee, United States

Research Memphis Associates, LLC /ID# 139674

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Memphis, Tennessee, United States

Clinical Trials Research Svcs /ID# 139707

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Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center /ID# 143537

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Dallas, Texas, United States

Eastern Virginia Med School /ID# 139647

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Norfolk, Virginia, United States

Clinical Research Partners, LL /ID# 143999

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North Chesterfield, Virginia, United States

Emerson Clinical Research /ID# 147373

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Vienna, Virginia, United States

Premier Clinical Research /ID# 148145

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Spokane, Washington, United States

The Ottawa Hospital /ID# 148695

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Ottawa, Ontario, Canada

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

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San Juan, Puerto Rico

Clinical Associates of Orlando /ID# 148123

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Orlando, Florida, United States

Omega Research Consultants /ID# 139648

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Orlando, Florida, United States

Ochsner Baptist Medical Center /ID# 139740

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New Orleans, Louisiana, United States

Unified Women's Clinical Resea /ID# 144721

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Winston-Salem, North Carolina, United States

Medical University of South Carolina /ID# 148754

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Charleston, South Carolina, United States

Clinical Trials Virginia, Inc. /ID# 139801

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Richmond, Virginia, United States

Atlanta Medical Research Insti /ID# 147117

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Alpharetta, Georgia, United States

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