Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids

AbbVie

Status and phase: Completed; Phase 2

Conditions: Uterine Fibroids; Heavy Uterine Bleeding

Treatments: Drug: Placebo; Drug: Estradiol/Norethindrone acetate (E2/NETA); Drug: Estradiol; Drug: Elagolix; Drug: Progesterone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01441635

M12-663

Details and patient eligibility

About

The purpose of this proof-of-concept study is to assess the safety and effectiveness of elagolix versus placebo to reduce uterine bleeding associated with uterine fibroids, and to reduce fibroid volume and uterine volume in premenopausal women 20 to 49 years of age with heavy uterine bleeding.

Enrollment: 271 patients

Sex: Female

Ages: 20 to 49 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subject is a pre-menopausal female 20 to 49 years of age.

• Subject has a diagnosis of uterine fibroids documented by a pelvic ultrasound assessed by a central reader and verification that a fibroid present met the following criteria:

  • At least 1 fibroid with diameter ≥ 2 cm (longest diameter), or multiple small fibroids with a total uterine volume of ≥ 200 cm³ to ≤ 2,500 cm³ (approximately 22 weeks' gestation) as documented by a centrally read ultrasound.
  • Only intramural, submucosal non-pedunculated, and subserosal fibroids qualified subjects for enrollment (intracavitary pedunculated fibroids were exclusionary).
  • Ultrasound procedures were performed during the Screening Period, and subjects were not randomized until the investigator reviewed the central reader results verifying the inclusion requirements.

• Subject has a history of regular menstrual cycles between 24 to 35 days.

• Subject has heavy uterine bleeding associated with uterine fibroids as evidenced by blood loss > 80 mL during 2 screening menstrual cycles, measured by the alkaline hematin method.

Exclusion criteria

• Subject has had a myomectomy, uterine artery embolization, or high intensity focused ultrasound for fibroid destruction within 1 year prior to randomization or any history of endometrial ablation.

• Subject has a history of osteoporosis or other metabolic bone disease.

• Subject shows evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including depression), or neurologic diseases or any uncontrolled medical illness such as uncontrolled type 2 diabetes.

• Subject has a history of clinically significant condition(s) including but not limited to:

  • Endometriosis
  • Epilepsy or seizures
  • Type 1 diabetes
  • Any cancer (except basal cell carcinoma of the skin), including breast or ovarian cancer or subject has taken any systemic cancer chemotherapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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271 participants in 10 patient groups, including a placebo group

Cohort 4 Elagolix 400 mg QD

Experimental group

Description:

Participants received elagolix 400 mg once a day (QD) for 3 months.

Treatment:

Drug: Elagolix

Cohort 4 Elagolix 100 mg BID

Experimental group

Description:

Participants received elagolix 100 mg twice a day (BID) for 3 months.

Treatment:

Drug: Elagolix

Cohort 4 Placebo

Placebo Comparator group

Description:

Participants received placebo to elagolix BID for 3 months.

Treatment:

Drug: Placebo

Cohort 1 Elagolix 200 mg BID

Experimental group

Description:

Participants received elagolix 200 mg twice a day for 3 months.

Treatment:

Drug: Elagolix

Cohort 1 Placebo

Placebo Comparator group

Description:

Participants received placebo to elagolix twice a day for 3 months.

Treatment:

Drug: Placebo

Cohort 3 Elagolix 200 mg BID + LD E2/NETA

Placebo Comparator group

Description:

Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.

Treatment:

Drug: Elagolix

Drug: Estradiol/Norethindrone acetate (E2/NETA)

Cohort 5 Elagolix 600 mg QD

Experimental group

Description:

Participants received elagolix 600 mg once a day for 3 months.

Treatment:

Drug: Elagolix

Cohort 2 Elagolix 300 mg BID

Experimental group

Description:

Participants received elagolix 300 mg twice a day for 3 months.

Treatment:

Drug: Elagolix

Cohort 2 Placebo

Experimental group

Description:

Participants received placebo to elagolix BID for 3 months.

Treatment:

Drug: Placebo

Cohort 6 Elagolix 300 mg BID + CEP

Experimental group

Description:

Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.

Treatment:

Drug: Progesterone

Drug: Elagolix

Drug: Estradiol