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

July 9, 2021 updated by: AbbVie (prior sponsor, Abbott)

Phase 2a Proof Of Concept Study to Evaluate the Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

271

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 49 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cohort 4 Elagolix 400 mg QD
Participants received elagolix 400 mg once a day (QD) for 3 months.
Drug: Elagolix
Elagolix tablets
Other Names:
  • ABT-620
EXPERIMENTAL: Cohort 4 Elagolix 100 mg BID
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Drug: Elagolix
Elagolix tablets
Other Names:
  • ABT-620
PLACEBO_COMPARATOR: Cohort 4 Placebo
Participants received placebo to elagolix BID for 3 months.
Drug: Placebo
Matching placebo tablets
EXPERIMENTAL: Cohort 1 Elagolix 200 mg BID
Participants received elagolix 200 mg twice a day for 3 months.
Drug: Elagolix
Elagolix tablets
Other Names:
  • ABT-620
PLACEBO_COMPARATOR: Cohort 1 Placebo
Participants received placebo to elagolix twice a day for 3 months.
Drug: Placebo
Matching placebo tablets
PLACEBO_COMPARATOR: 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.
Drug: Elagolix
Elagolix tablets
Other Names:
  • ABT-620
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.
Other Names:
  • Activella®
EXPERIMENTAL: Cohort 5 Elagolix 600 mg QD
Participants received elagolix 600 mg once a day for 3 months.
Drug: Elagolix
Elagolix tablets
Other Names:
  • ABT-620
EXPERIMENTAL: Cohort 2 Elagolix 300 mg BID
Participants received elagolix 300 mg twice a day for 3 months.
Drug: Elagolix
Elagolix tablets
Other Names:
  • ABT-620
EXPERIMENTAL: Cohort 2 Placebo
Participants received placebo to elagolix BID for 3 months.
Drug: Placebo
Matching placebo tablets
EXPERIMENTAL: 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.
Drug: Elagolix
Elagolix tablets
Other Names:
  • ABT-620
Drug: Estradiol
1.0 mg micronized estradiol tablets administered once a day
Other Names:
  • Estrace®
Drug: Progesterone
Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle
Other Names:
  • Prometrium®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
Time Frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
Time Frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

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)
Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
Time Frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

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)
Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment
Time Frame: The last 28 days of treatment (approximately days 61 to 90)

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

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)
Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3
Time Frame: Baseline and Month 3

The percentage of subjects with changes in hemoglobin concentration from Baseline to Month 3 in each of the following categories:

  • No change from baseline in hemoglobin
  • Decrease from baseline in hemoglobin ≥ -0.5 g/dL
  • Decrease from baseline in hemoglobin ≥ -1.0 g/dL
  • Increase from baseline in hemoglobin ≥ 0.5 g/dL
  • Increase from baseline in hemoglobin ≥ 1.0 g/dL

The above categories are not all mutually exclusive or exhaustive.
Baseline and Month 3
Change in Hemoglobin Concentration From Baseline to Month 3
Time Frame: Baseline and Month 3
Baseline and Month 3
Change From Baseline to Month 3 in Uterine Bleeding Score
Time Frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)

Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

  • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
  • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
  • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
  • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
  • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
  • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.
Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding
Time Frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)

Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

  • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
  • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
  • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
  • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
  • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
  • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

A day with any uterine bleeding is defined as a days with a bleeding score ≥ 1.
Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding
Time Frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)

Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

  • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
  • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
  • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
  • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
  • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
  • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

A day with moderate to very heavy bleeding is defined as a days with a bleeding score ≥ 3.
Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3
Time Frame: Month 3 (average bleeding score over days 61 to 90)

Participants recorded the previous days' presence and severity of bleeding every morning in an eDiary according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

  • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
  • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
  • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
  • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
  • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
  • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

Any bleeding is defined as a score ≥ 1 and moderate to very heavy bleeding is defined as a score ≥ 3.
Month 3 (average bleeding score over days 61 to 90)
Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment
Time Frame: The last 56 days of treatment (approximately days 33 to 90)

Suppression of bleeding is defined as no record of bleeding (spotting allowed) in the e-diary and no record of bleeding Indicated in the alkaline hematin data during the last 56 days of treatment.

Amenorrhea is defined as no record of bleeding or spotting indicated in the e-diary and no record of bleeding or spotting Indicated in the alkaline hematin data during the last 56 days of treatment.
The last 56 days of treatment (approximately days 33 to 90)
Percent Change From Baseline to Month 3 in Uterine Volume
Time Frame: Baseline and month 3
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Baseline and month 3
Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit
Time Frame: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid
Time Frame: Baseline and month 3
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Baseline and month 3
Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit
Time Frame: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)
Time Frame: Baseline and month 3

The UFS-QoL is a disease-specific, self-administered, validated questionnaire developed to evaluate the symptoms associated with uterine fibroids and their impact on health-related quality of life (HRQL) in women with symptomatic uterine fibroids. The questionnaire consists of 37 questions, divided into 2 parts: 1) an 8-item symptom severity scale and 2) a 29-item HRQL subscale comprising 6 domains (concern, activities, energy/mood, control, self-consiousness, and sexual function), with a 4-week recall. All items are scored on a 5-point scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores were summed and transformed into a 0 to 100 point scale to provide a total score for each of the 2 components.

Lower symptom severity scores indicate better quality of life and higher total HRQL scores indicate better quality of life.
Baseline and month 3
Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores
Time Frame: Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90)
The uterine fibroid daily symptom scale is self-administered questionnaire, with a scale that ranges from 0 to 10 for the symptoms of pelvic pain, fatigue, and cramping and the impact of uterine fibroids on the subject's daily life, with 0 being the absence of the symptom and 10 being the worst severity of the symptoms or completely preventing the subjects from performing daily activities. Participants self-reported values daily in the e-Diary.
Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90)
Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0
Time Frame: Baseline and month 3

The Subject Intention Questionnaire (SSIQ) is a non-validated, exploratory questionnaires intended to evaluate the subject's intent to undergo surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to consider surgery) to 10 (very likely to consider surgery).

SSIQ included the 2 following questions:

  1. How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now?
  2. How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now?
Baseline and month 3
Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0
Time Frame: Baseline and month 3

The Physician Intention Questionnaire (PSIQ) is a non-validated, exploratory questionnaire intended to evaluate the investigator's intent to recommend surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to recommend surgery) to 10 (very likely to recommend surgery).

The PSIQ included the 2 following questions:

  1. How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now?
  2. How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now?
Baseline and month 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie (prior sponsor, Abbott)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 8, 2011

Primary Completion (ACTUAL)

November 1, 2013

Study Completion (ACTUAL)

May 17, 2014

Study Registration Dates

First Submitted

September 6, 2011

First Submitted That Met QC Criteria

September 26, 2011

First Posted (ESTIMATE)

September 28, 2011

Study Record Updates

Last Update Posted (ACTUAL)

July 13, 2021

Last Update Submitted That Met QC Criteria

July 9, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M12-663

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

IPD Sharing Time Frame

Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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