An Extension Study to Evaluate the Efficacy and Safety of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Study Overview
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Brief Summary
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This is an extension study for women who have already received six months of treatment in the phase III clinical trial M12-815 (NCT02654054) or M12-817 (NCT02691494), and will evaluate the long-term efficacy and safety of elagolix administered alone and in combination with estradiol/norethindrone acetate for an additional six months in the treatment of heavy menstrual bleeding associated with uterine fibroids.

Official Title
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Extension Study to Evaluate the Efficacy and Safety of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Conditions
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Uterine Fibroids, Heavy Menstrual Bleeding

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has completed the 6-Month Treatment Period of their respective Pivotal Study (either Study M12-815 or Study M12-817). Participant did not meet removal criteria in bone mineral density (BMD) decrease in the spine, total hip and femoral neck at Month 6 of the Treatment Period of their respective Pivotal Study Participant has negative urine and/or serum pregnancy test(s) results were consistently negative during the Treatment Period of their respective Pivotal Study and prior to first dose in this study. Participant's endometrial biopsy from the Month 6 Visit of their respective Pivotal Study shows no clinically significant endometrial pathology. Exclusion Criteria: Participant met criteria for removal from therapy in her respective Pivotal Study. Participant is planning a pregnancy within the next 18 months. Participant has current suicidal markers as noted at the Month 6 visit of her respective pivotal study. Participant has any new medical conditions that may be unsuitable for participation. Participant is using any systemic corticosteroids for over 14 days 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 |
| --- | --- |
| Experimental: Elagolix plus Estradiol/Norethindrone Acetate (E2/NETA)<br>Elagolix 300 mg twice daily (BID) and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) once daily (QD) | Drug: Estradiol/Norethindrone Acetate<br>* capsules<br>Drug: Elagolix<br>* film-coated tablets<br>* Other names: elagolix sodium;|
| 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;|

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 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. | From Month 0 (Baseline in Pivotal Study) to Final Month of Treatment Period (up through Month 6 in Extension Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period | Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, 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 in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through Month 6) | 
| Percent Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period | Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, 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 in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through 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. | Final Month of Treatment Period (up through Month 6) | 
| Percentage of Participants With Baseline Hemoglobin Concentration ≤ 10.5 g/dL and an Increase From Baseline > 2 g/dL at Month 6 During the Treatment Period |  | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elagolix, Uterine Fibroids, Heavy Menstrual Bleeding, Elagolix Sodium, Elagolix plus Norethindrone Acetate