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

• 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

Study Timeline

• Study Start: 2015-12-22
• Study First Submitted: 2016-01-08
• Study First Submitted QC: 2016-01-11
• Study First Posted: 2016-01-13
• Primary Completion: 2018-01-18
• Disposition First Submitted: 2018-12-03
• Disposition First Submitted QC: 2018-12-03
• Disposition First Posted: 2018-12-05
• Study Completion: 2018-12-12
• Status Verified: 2020-06
• Results First Submitted: 2020-06-09
• Results First Submitted QC: 2020-06-09
• Last Update Submitted: 2020-06-09
• Results First Posted: 2020-06-29
• Last Update Posted: 2020-06-29

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

Group	Intervention	Description
Elagolix	Elagolix	Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
Placebo	Placebo for Estradiol/Norethindrone Acetate	Placebo for both elagolix twice daily (BID) and norethindrone acetate (E2/NETA) once daily (QD)
Elagolix	Placebo for Estradiol/Norethindrone Acetate	Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
Elagolix + E2/NETA	Estradiol/Norethindrone Acetate	Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
Placebo	Placebo for Elagolix	Placebo for both elagolix twice daily (BID) and norethindrone acetate (E2/NETA) once daily (QD)
Elagolix + E2/NETA	Elagolix	Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Meeting the Criteria for Responder	Final 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

Name	Time	Method
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	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 Month	Final 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 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
Change From Baseline in MBL Volume to Month 1	Month 0 (Baseline), Month 1

Trial Locations

Locations (96)

Summers, Birmingham, AL /ID# 139684; 🇺🇸 Birmingham, Alabama, United States

University of South Alabama /ID# 148763; 🇺🇸 Mobile, Alabama, United States

WCCT Global, LLC /ID# 145666; 🇺🇸 Costa Mesa, California, United States

American Clinical Trials /ID# 147374; 🇺🇸 Hawaiian Gardens, California, United States

Grossmont Ctr Clin Research /ID# 144011; 🇺🇸 La Mesa, California, United States

Long Beach Clinical Trial Serv /ID# 152424; 🇺🇸 Long Beach, California, United States

National Research Institute /ID# 151629; 🇺🇸 Los Angeles, California, United States

University of California, Los Angeles /ID# 144107; 🇺🇸 Los Angeles, California, United States

Beach OBGYN Medical Group /ID# 151414; 🇺🇸 Newport Beach, California, United States

Advanced RX Clinical Research /ID# 149168; 🇺🇸 Westminster, California, United States

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