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

AbbVie

Status and phase: Completed; Phase 3

Conditions: Uterine Fibroids; Heavy Menstrual Bleeding

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03271489

M16-283

Details and patient eligibility

About

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.

Full 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).

Enrollment: 478 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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478 participants in 2 patient groups, including a placebo group

Elagolix plus estradiol (E2)/norethindrone acetate (NETA)

Experimental group

Treatment:

Drug: Estradiol /norethindrone acetate (E2/NETA)

Drug: Elagolix

Placebo

Placebo Comparator group

Treatment:

Other: E2/NETA Placebo

Other: Elagolix Placebo