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)

Uterine Fibroids Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02691494
• Other study ID #: M12-817
• Status: Completed
• Phase: Phase 3
• Start date: February 3, 2016
• Est. completion date: January 23, 2019

Study information

• Verified date: July 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 378
• Est. completion date: January 23, 2019
• Est. primary completion date: February 14, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 51 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heavy Menstrual Bleeding
• Hemorrhage
• Leiomyoma
• Menorrhagia
• Uterine Fibroids

Intervention

Drug:
• Elagolix
Film-coated tablets
• Placebo for Estradiol/Norethindrone Acetate
Placebo capsules
• Estradiol/Norethindrone Acetate
Commercially-available E2/NETA tablets were over-encapsulated to maintain study blinding.
• Placebo for Elagolix
Film-coated placebo tablets

Locations

Country	Name	City	State
Canada	Medicor Research Inc. /ID# 153406	Sudbury	Ontario
Canada	Victory Reproductive Care /ID# 150247	Windsor	Ontario
United States	Paramount Research Solutions /ID# 149291	Alpharetta	Georgia
United States	Agile Clinical Research Trials /ID# 167074	Atlanta	Georgia
United States	Atlanta Women's Research Inst /ID# 144303	Atlanta	Georgia
United States	Mount Vernon Clinical Res, LLC /ID# 144297	Atlanta	Georgia
United States	Georgia Regents University /ID# 144295	Augusta	Georgia
United States	Masters of Clinical Research, Inc. /ID# 167400	Augusta	Georgia
United States	Lotus Gynecology /ID# 149140	Austin	Texas
United States	Ideal Clinical Research Inc. /ID# 149757	Aventura	Florida
United States	Baltimore Suburban Health /ID# 154638	Baltimore	Maryland
United States	Inquest Clinical Research /ID# 149755	Baytown	Texas
United States	Clinical Inquest Center Ltd /ID# 148728	Beavercreek	Ohio
United States	Alabama Clinical Therapeutics, LLC /ID# 152258	Birmingham	Alabama
United States	Seffner Premier Health Care, P /ID# 167480	Brandon	Florida
United States	Holston Medical Group /ID# 149763	Bristol	Tennessee
United States	Montefiore Medical Center /ID# 149582	Bronx	New York
United States	SUNY Downstate Medical Center /ID# 144311	Brooklyn	New York
United States	Core Healthcare Group /ID# 151016	Cerritos	California
United States	Chattanooga Medical Research /ID# 145667	Chattanooga	Tennessee
United States	University of Chicago /ID# 152257	Chicago	Illinois
United States	CTI Clinical Research Center /ID# 149761	Cincinnati	Ohio
United States	The Christ Hospital /ID# 150104	Cincinnati	Ohio
United States	Olympian Clinical Research /ID# 149756	Clearwater	Florida
United States	Clinical Trials Management, LLC - Covington /ID# 144314	Covington	Louisiana
United States	Texas Health Presbyterian Hosp /ID# 149142	Dallas	Texas
United States	Alpha Research Associates LLC /ID# 152471	Dayton	Ohio
United States	Choice Research, LLC /ID# 150988	Dothan	Alabama
United States	Diagnamics Inc. /ID# 152469	Encinitas	California
United States	Brown, Pearson, Guepet Gynecology /ID# 151020	Fairhope	Alabama
United States	NECCR Fall River LLC /ID# 149584	Fall River	Massachusetts
United States	Duplicate_Unified Women's Clinical Research-Fayetteville /ID# 149587	Fayetteville	North Carolina
United States	KO Clinical Research, LLC /ID# 144299	Fort Lauderdale	Florida
United States	Women's Health Advantage /ID# 144301	Fort Wayne	Indiana
United States	Southampton Women's Health /ID# 152325	Franklin	Virginia
United States	University of Florida /ID# 149751	Gainesville	Florida
United States	Womens Health Center /ID# 154209	Glen Burnie	Maryland
United States	Unified Women's Clinical Research-Greensboro /ID# 149588	Greensboro	North Carolina
United States	Pinewest Ob-Gyn, Inc. /ID# 145671	High Point	North Carolina
United States	Chattanooga Women for Women /ID# 167051	Hixson	Tennessee
United States	Baylor College of Medicine /ID# 149141	Houston	Texas
United States	BI Research Center /ID# 149143	Houston	Texas
United States	Centex Studies, Inc. - Houston /ID# 150106	Houston	Texas
United States	The Woman's Hospital of Texas /ID# 144319	Houston	Texas
United States	HCP Clinical Research LLC /ID# 154434	Huntington Beach	California
United States	Womens Healthcare Assoc, DBA /ID# 149762	Idaho Falls	Idaho
United States	The Jackson Clinic, PA /ID# 145670	Jackson	Tennessee
United States	Solutions Through Adv Rch /ID# 151021	Jacksonville	Florida
United States	Meridien Research /ID# 167100	Kenneth City	Florida
United States	Alliance Research Centers /ID# 149752	Laguna Hills	California
United States	FMC Science /ID# 151802	Lampasas	Texas
United States	Accent Clinical Trials /ID# 149753	Las Vegas	Nevada
United States	Family Medical Associates /ID# 145668	Levittown	Pennsylvania
United States	University of California, Los Angeles /ID# 149760	Los Angeles	California
United States	Bluegrass Clinical Research /ID# 150103	Louisville	Kentucky
United States	Maryland Ctr for Sexual Health /ID# 149778	Lutherville	Maryland
United States	The Womens Physician Group /ID# 144317	Memphis	Tennessee
United States	Advanced Clinical Research /ID# 149767	Meridian	Idaho
United States	Mesa Obstetricians and Gynecol /ID# 149139	Mesa	Arizona
United States	Invictus Clinical Research Group,LLC /ID# 141859	Miami	Florida
United States	Precision Research Org, LLC /ID# 144335	Miami Lakes	Florida
United States	Mobile, Ob-Gyn, P.C. /ID# 144294	Mobile	Alabama
United States	Access Clinical Trials, Inc. /ID# 167333	Nashville	Tennessee
United States	Jersey Shore University Medical Center /ID# 149779	Neptune	New Jersey
United States	Eastern Carolina Women's Centr /ID# 144309	New Bern	North Carolina
United States	Women Under Study, LLC /ID# 144312	New Orleans	Louisiana
United States	Suncoast Clinical Research /ID# 149765	New Port Richey	Florida
United States	Manhattan Medical Research /ID# 167077	New York	New York
United States	Weill Cornell Medicine /ID# 149585	New York	New York
United States	Tidewater Physicians for Women /ID# 144321	Norfolk	Virginia
United States	Futura Research, Inc. /ID# 149759	Norwalk	California
United States	Affinity Clinical Research /ID# 167119	Oak Brook	Illinois
United States	Center for Women's Research, Inc /ID# 144300	Palos Heights	Illinois
United States	Clinical Research of Philadelphia, LLC /ID# 151015	Philadelphia	Pennsylvania
United States	University of Pennsylvania /ID# 149586	Philadelphia	Pennsylvania
United States	Willowbend Health and Wellness /ID# 144318	Plano	Texas
United States	All Wmns HC of West Broward /ID# 144298	Plantation	Florida
United States	Wake Research Associates, LLC /ID# 144307	Raleigh	North Carolina
United States	Zain Research /ID# 151018	Richland	Washington
United States	Alliance Womens Health /ID# 152468	Richmond	Virginia
United States	Clinical Research Partners, LLC /ID# 144310	Richmond	Virginia
United States	Saginaw Valley Med Res Group /ID# 149768	Saginaw	Michigan
United States	Oncova Clinical Research, Inc. /ID# 149764	Saint Cloud	Florida
United States	Clinical Trials of Texas,Inc. /ID# 144322	San Antonio	Texas
United States	Farid Yasharpour MD Medical Co /ID# 149770	San Fernando	California
United States	Physician Care Clin. Res., LLC /ID# 149766	Sarasota	Florida
United States	Meridian Clinical Research, LLC /ID# 149144	Savannah	Georgia
United States	Virginia Mason Medical Center /ID# 149758	Seattle	Washington
United States	Gyn-Care, Inc. /ID# 149341	Smyrna	Georgia
United States	Qps-Mra, Llc /Id# 144325	South Miami	Florida
United States	Rowan University SOM /ID# 152697	Stratford	New Jersey
United States	Martin Health System Center /ID# 152263	Stuart	Florida
United States	Atlanta Gynecology Research Institute /ID# 151014	Suwanee	Georgia
United States	University of South Florida /ID# 149754	Tampa	Florida
United States	Visions Clinical Research-Tucs /ID# 151017	Tucson	Arizona
United States	Clinical Trial Investigators /ID# 152470	Tustin	California
United States	Bayview Research Group LLC /ID# 153799	Valley Village	California
United States	Emerson Clinical Research Inst /ID# 152348	Washington	District of Columbia
United States	Center of Reproductive Medicin /ID# 167235	Webster	Texas
United States	Axcess Medical Research /ID# 149769	Wellington	Florida
United States	Virtus Research Consultant,LLC /ID# 144296	Wellington	Florida
United States	The Iowa Clinic /ID# 150105	West Des Moines	Iowa
United States	Reading Hosp Clncl Trials Ofc /ID# 149583	West Reading	Pennsylvania
United States	Comprehensive Womens Care /ID# 144306	Westerville	Ohio
United States	PRN Professional Research Network of Kansas, LLC /ID# 152265	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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