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

NCT01441635 | Completed Phase 2 Results FDA Drug

• 1 other identifier: M12-663
• Study Type: interventional
• Target: 271
• Locations: 0 countries
• Sites: N/A

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

Keywords

Uterine Fibroids; Heavy Uterine Bleeding; Elagolix; Menorrhagia; ABT-620; Leiomyomata; Elagolix sodium

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)

  The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.

  Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

Secondary Outcomes (19)

• Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)

  Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

• Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment

  Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

• Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment

  The last 28 days of treatment (approximately days 61 to 90)

• Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment

  Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

• Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3

  Baseline and Month 3

Study Arms (10)

Cohort 4 Elagolix 400 mg QD

EXPERIMENTAL

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

Drug: Elagolix

Cohort 4 Elagolix 100 mg BID

EXPERIMENTAL

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

Drug: Elagolix

Cohort 4 Placebo

PLACEBO COMPARATOR

Participants received placebo to elagolix BID for 3 months.

Drug: Placebo

Cohort 1 Elagolix 200 mg BID

EXPERIMENTAL

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

Drug: Elagolix

Cohort 1 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Cohort 3 Elagolix 200 mg BID + LD E2/NETA

PLACEBO COMPARATOR

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.

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

Cohort 5 Elagolix 600 mg QD

EXPERIMENTAL

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

Drug: Elagolix

Cohort 2 Elagolix 300 mg BID

EXPERIMENTAL

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

Drug: Elagolix

Cohort 2 Placebo

EXPERIMENTAL

Participants received placebo to elagolix BID for 3 months.

Drug: Placebo

Cohort 6 Elagolix 300 mg BID + CEP

EXPERIMENTAL

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.

Drug: Elagolix; Drug: Estradiol; Drug: Progesterone

Interventions

Elagolix DRUG

Elagolix tablets

Also known as: ABT-620

Cohort 1 Elagolix 200 mg BID; Cohort 2 Elagolix 300 mg BID; Cohort 3 Elagolix 200 mg BID + LD E2/NETA; Cohort 4 Elagolix 100 mg BID; Cohort 4 Elagolix 400 mg QD; Cohort 5 Elagolix 600 mg QD; Cohort 6 Elagolix 300 mg BID + CEP

Placebo DRUG

Matching placebo tablets

Cohort 1 Placebo; Cohort 2 Placebo; Cohort 4 Placebo

Estradiol/Norethindrone acetate (E2/NETA) 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.

Also known as: Activella®

Cohort 3 Elagolix 200 mg BID + LD E2/NETA

Estradiol DRUG

1.0 mg micronized estradiol tablets administered once a day

Also known as: Estrace®

Cohort 6 Elagolix 300 mg BID + CEP

Progesterone DRUG

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

Also known as: Prometrium®

Cohort 6 Elagolix 300 mg BID + CEP

Eligibility Criteria

• Age: 20 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Related Publications (2)

• 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.

  PMID: 28579415 BACKGROUND

• 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.

  PMID: 27733082 DERIVED

MeSH Terms

Conditions

Leiomyoma; Menorrhagia

Interventions

elagolix; Estradiol; Norethindrone Acetate; estradiol, norethindrone drug combination; Progesterone

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norethindrone; Norpregnenes; Norpregnanes; Norsteroids; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2011
• First Posted: September 28, 2011
• Study Start: September 8, 2011
• Primary Completion: November 1, 2013
• Study Completion: May 17, 2014
• Last Updated: July 13, 2021
• Results First Posted: July 15, 2020

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.