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

NCT ID: NCT01441635

Last Updated: 2021-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 271 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-08
• Study Completion Date: 2014-05-17

Brief Summary

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.

Conditions

Heavy Uterine Bleeding; Uterine Fibroids

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cohort 4 Elagolix 400 mg QD

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

Group Type: EXPERIMENTAL

Elagolix

Intervention Type: DRUG

Elagolix tablets

Cohort 4 Elagolix 100 mg BID

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

Group Type: EXPERIMENTAL

Elagolix

Intervention Type: DRUG

Elagolix tablets

Cohort 4 Placebo

Participants received placebo to elagolix BID for 3 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo tablets

Cohort 1 Elagolix 200 mg BID

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

Group Type: EXPERIMENTAL

Elagolix

Intervention Type: DRUG

Elagolix tablets

Cohort 1 Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo tablets

Cohort 3 Elagolix 200 mg BID + LD E2/NETA

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.

Group Type: PLACEBO_COMPARATOR

Elagolix

Intervention Type: DRUG

Elagolix tablets

Estradiol/Norethindrone acetate (E2/NETA)

Intervention Type: DRUG

A continuous once-daily oral tablet containing estrogen and progestin; the low-dose strength contains estradiol 0.5 mg and norethindrone acetate 0.1 mg.

Cohort 5 Elagolix 600 mg QD

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

Group Type: EXPERIMENTAL

Elagolix

Intervention Type: DRUG

Elagolix tablets

Cohort 2 Elagolix 300 mg BID

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

Group Type: EXPERIMENTAL

Elagolix

Intervention Type: DRUG

Elagolix tablets

Cohort 2 Placebo

Participants received placebo to elagolix BID for 3 months.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo tablets

Cohort 6 Elagolix 300 mg BID + CEP

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.

Group Type: EXPERIMENTAL

Elagolix

Intervention Type: DRUG

Elagolix tablets

Estradiol

Intervention Type: DRUG

1.0 mg micronized estradiol tablets administered once a day

Progesterone

Intervention Type: DRUG

Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle

Interventions

Elagolix

Elagolix tablets

Intervention Type: DRUG

Placebo

Matching placebo tablets

Intervention Type: DRUG

Estradiol/Norethindrone acetate (E2/NETA)

A continuous once-daily oral tablet containing estrogen and progestin; the low-dose strength contains estradiol 0.5 mg and norethindrone acetate 0.1 mg.

Intervention Type: DRUG

Estradiol

1.0 mg micronized estradiol tablets administered once a day

Intervention Type: DRUG

Progesterone

Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle

Intervention Type: DRUG

Other Intervention Names

ABT-620; Activella®; Estrace®; Prometrium®

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

References

Archer DF, Stewart EA, Jain RI, Feldman RA, Lukes AS, North JD, Soliman AM, Gao J, Ng JW, Chwalisz K. Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study. Fertil Steril. 2017 Jul;108(1):152-160.e4. doi: 10.1016/j.fertnstert.2017.05.006. Epub 2017 Jun 1.

Reference Type: BACKGROUND

PMID: 28579415 (View on PubMed)

Coyne KS, Soliman AM, Margolis MK, Thompson CL, Chwalisz K. Validation of the 4 week recall version of the Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) Questionnaire. Curr Med Res Opin. 2017 Feb;33(2):193-200. doi: 10.1080/03007995.2016.1248382. Epub 2016 Nov 18.

Reference Type: DERIVED

PMID: 27733082 (View on PubMed)

Other Identifiers

M12-663

Identifier Type: -

Identifier Source: org_study_id