Long-Term Safety Study 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

Interventions: Drug: Elagolix
Other: E2/NETA Placebo
Drug: Estradiol /norethindrone acetate (E2/NETA)
Other: Elagolix Placebo

Brief Summary: This randomized multicenter phase 3b study seeks to evaluate the safety of elagolix in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. This study was double-blind (DB) during the first 12 months and open-label (OL) for the next 36 months.

Detailed Description: 478 participants were randomly assigned at a ratio of 2:1 to the following treatment groups:

1. Elagolix 300 mg twice daily (BID) plus estradiol 1.0 mg/norethindrone acetate 0.5 mg (E2/NETA) once daily (QD) for 48 months, followed by 12 months PTFU

2. Placebo for 12 months, followed by elagolix 300 mg BID plus E2/NETA QD for 36 months, followed by 12 months PTFU

This study was double-blinded during the first 12 months and open-label for the next 36 months. Participants entered up to 12 months of PTFU after completing treatment Month 48 (or at any time a participant prematurely discontinued treatment).

Recruitment & Eligibility

Inclusion Criteria

Participant is a premenopausal female at the time of Screening.
Participant has a diagnosis of uterine fibroids documented by a Pelvic Ultrasound [Transabdominal ultrasound (TAU) or transvaginal ultrasound (TVU)].
Participant has Heavy Menstrual Bleeding (HMB) associated with uterine fibroids as evidenced by Menstrual Blood Loss (MBL) > 80 mL during each of two screening menses as measured by the alkaline hematin method.
Participant has negative urine and/or serum pregnancy test during Washout (if applicable) and/or Screening and just prior to first dose.
Participant has an adequate endometrial biopsy performed during Screening, the results of which show no clinical significant endometrial pathology.

Exclusion Criteria

Participant has screening pelvic ultrasound or Saline Infusion Sonohysterography (SIS) results that show a clinically significant gynecological disorder.
Participant has history of osteoporosis or other metabolic bone disease.
Participant has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.
Participant has a history of major depression or post-traumatic stress disorder (PTSD) episode within 2 years of screening, OR a history of other major psychiatric disorder at any time (e.g., schizophrenia, bipolar disorder).
Participant 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 intra-articular injectable (for occasional use) corticosteroids are allowed.

Arm && Interventions

Group	Intervention	Description
Elagolix plus estradiol (E2)/norethindrone acetate (NETA)	Elagolix	-
Elagolix plus estradiol (E2)/norethindrone acetate (NETA)	Estradiol /norethindrone acetate (E2/NETA)	-
Placebo	E2/NETA Placebo	-
Placebo	Elagolix Placebo	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs)	Baseline to 60 months	An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. AEs during the 12-month DB period were defined as any AEs with onset on/after first dose of study drug during the DB period and no more than 30 days after the last dose of study drug for participants who discontinued early during the DB period, or until the first dose of study drug in the OL period for participants who entered the OL Treatment Period. AEs during the OL period were defined as AEs with onset on/after first dose of study drug during the OL period and no more than 30 days after the last dose of study drug. During the post-treatment follow-up (PTFU) period, adverse events were collected from 30 days post-last dose until end of study. Safety reporting during the PTFU period included AESIs. Other AEs may have also been reported.

Secondary Outcome Measures

Name	Time	Method
Bone Mineral Density (BMD) Recovery After up to 48 Months of Treatment	Baseline through Month 60	Percent Recovery of BMD after 6 and 12 months of post-treatment follow-up (PTFU) for Spine, Total Hip, and Femoral Neck. BMD assessments were measured by dual X-ray absorptiometry (DXA). Analysis excludes participants who switched machine manufacturer type. Percent recovery is defined as 100\*(% change from Baseline to final on-treatment assessment - % change from Baseline to post-treatment visit) / (% change from Baseline to final on treatment assessment) and is defined only for subjects with BMD decrease at final on-treatment assessment.

Locations (157): Alabama Clinical Therapeutics /ID# 160835
🇺🇸
Birmingham, Alabama, United States
Alabama Clinical Therapeutics /ID# 160927
🇺🇸
Birmingham, Alabama, United States
Choice Research, LLC /ID# 161498
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Dothan, Alabama, United States
Southern Women's Specialists PC /ID# 161531
🇺🇸
Fairhope, Alabama, United States
E Squared Research /ID# 163645
🇺🇸
Huntsville, Alabama, United States
Women's Health Alliance of Mobile /ID# 161443
🇺🇸
Mobile, Alabama, United States
Mobile, OBGYN P.C. /ID# 161530
🇺🇸
Mobile, Alabama, United States
Mesa Obstetricians and Gynecologists /ID# 160955
🇺🇸
Mesa, Arizona, United States
Noble Clinical Research /ID# 166949
🇺🇸
Tucson, Arizona, United States
Vision's Clinical Research-Tucson /ID# 161508
🇺🇸
Tucson, Arizona, United States
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Alabama Clinical Therapeutics /ID# 160835
🇺🇸Birmingham, Alabama, United States