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)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Uterine Fibroids, Heavy Menstrual Bleeding

Intervention / Treatment
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* Drug: Elagolix
* Drug: Placebo for Estradiol/Norethindrone Acetate
* Drug: Estradiol/Norethindrone Acetate
* Drug: Placebo for Elagolix


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 51 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo for both elagolix twice daily (BID) and norethindrone acetate (E2/ NETA) once daily (QD) | Drug: Placebo for Estradiol/Norethindrone Acetate<br>* Placebo capsules<br>Drug: Placebo for Elagolix<br>* Film-coated placebo tablets<br>|
| Experimental: Elagolix<br>Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD | Drug: Elagolix<br>* Film-coated tablets<br>* Other names: elagolix sodium;Drug: Placebo for Estradiol/Norethindrone Acetate<br>* Placebo capsules<br>|
| Experimental: Elagolix + E2/NETA<br>Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD | Drug: Elagolix<br>* Film-coated tablets<br>* Other names: elagolix sodium;Drug: Estradiol/Norethindrone Acetate<br>* Commercially-available E2/NETA tablets were over-encapsulated to maintain study blinding.<br>* Other names: E2/NETA;|

What is the study measuring?
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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 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elagolix Sodium, Heavy uterine bleeding, Heavy menstrual bleeding (HMB), Leiomyomata, Menorrhagia, ABT-620, Elagolix + E2/NETA (Elagolix + Norethindrone acetate), Elagolix