Back to resultsSafety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids
Primary Purpose
Heavy Uterine Bleeding, Uterine Fibroids
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Elagolix
Placebo
Estradiol/Norethindrone acetate (E2/NETA)
Estradiol
Progesterone
Sponsored by
About this trial
This is an interventional treatment trial for Heavy Uterine Bleeding focused on measuring Uterine Fibroids, Heavy Uterine Bleeding, Elagolix, Menorrhagia, ABT-620, Leiomyomata, Elagolix sodium
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 4 Elagolix 400 mg QD
Cohort 4 Elagolix 100 mg BID
Cohort 4 Placebo
Cohort 1 Elagolix 200 mg BID
Cohort 1 Placebo
Cohort 3 Elagolix 200 mg BID + LD E2/NETA
Cohort 5 Elagolix 600 mg QD
Cohort 2 Elagolix 300 mg BID
Cohort 2 Placebo
Cohort 6 Elagolix 300 mg BID + CEP
Arm Description
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
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.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Percent 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.
Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
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.
Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment
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.
Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
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.
Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at 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.
Change in Hemoglobin Concentration From Baseline to Month 3
Change From Baseline to Month 3 in Uterine Bleeding Score
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.
Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding
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.
Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding
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.
Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3
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.
Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment
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.
Percent Change From Baseline to Month 3 in Uterine Volume
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)
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.
Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores
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.
Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0
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:
How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now?
How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now?
Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0
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:
How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now?
How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now?
Full Information
NCT ID
NCT01441635
First Posted
September 6, 2011
Last Updated
July 9, 2021
Sponsor
AbbVie (prior sponsor, Abbott)
1. Study Identification
Unique Protocol Identification Number
NCT01441635
Brief Title
Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
September 8, 2011 (Actual)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
May 17, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heavy Uterine Bleeding, Uterine Fibroids
Keywords
Uterine Fibroids, Heavy Uterine Bleeding, Elagolix, Menorrhagia, ABT-620, Leiomyomata, Elagolix sodium
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
271 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 4 Elagolix 400 mg QD
Arm Type
Experimental
Arm Description
Participants received elagolix 400 mg once a day (QD) for 3 months.
Arm Title
Cohort 4 Elagolix 100 mg BID
Arm Type
Experimental
Arm Description
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Arm Title
Cohort 4 Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo to elagolix BID for 3 months.
Arm Title
Cohort 1 Elagolix 200 mg BID
Arm Type
Experimental
Arm Description
Participants received elagolix 200 mg twice a day for 3 months.
Arm Title
Cohort 1 Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo to elagolix twice a day for 3 months.
Arm Title
Cohort 3 Elagolix 200 mg BID + LD E2/NETA
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Cohort 5 Elagolix 600 mg QD
Arm Type
Experimental
Arm Description
Participants received elagolix 600 mg once a day for 3 months.
Arm Title
Cohort 2 Elagolix 300 mg BID
Arm Type
Experimental
Arm Description
Participants received elagolix 300 mg twice a day for 3 months.
Arm Title
Cohort 2 Placebo
Arm Type
Experimental
Arm Description
Participants received placebo to elagolix BID for 3 months.
Arm Title
Cohort 6 Elagolix 300 mg BID + CEP
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Elagolix
Other Intervention Name(s)
ABT-620
Intervention Description
Elagolix tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo tablets
Intervention Type
Drug
Intervention Name(s)
Estradiol/Norethindrone acetate (E2/NETA)
Other Intervention Name(s)
Activella®
Intervention Description
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
Intervention Name(s)
Estradiol
Other Intervention Name(s)
Estrace®
Intervention Description
1.0 mg micronized estradiol tablets administered once a day
Intervention Type
Drug
Intervention Name(s)
Progesterone
Other Intervention Name(s)
Prometrium®
Intervention Description
Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle
Primary Outcome Measure Information:
Title
Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
Description
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.
Time Frame
Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Secondary Outcome Measure Information:
Title
Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
Description
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.
Time Frame
Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Title
Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
Description
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.
Time Frame
Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Title
Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment
Description
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.
Time Frame
The last 28 days of treatment (approximately days 61 to 90)
Title
Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
Description
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.
Time Frame
Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Title
Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3
Description
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.
Time Frame
Baseline and Month 3
Title
Change in Hemoglobin Concentration From Baseline to Month 3
Time Frame
Baseline and Month 3
Title
Change From Baseline to Month 3 in Uterine Bleeding Score
Description
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.
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)
Title
Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding
Description
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.
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)
Title
Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding
Description
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.
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)
Title
Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3
Description
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.
Time Frame
Month 3 (average bleeding score over days 61 to 90)
Title
Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment
Description
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.
Time Frame
The last 56 days of treatment (approximately days 33 to 90)
Title
Percent Change From Baseline to Month 3 in Uterine Volume
Description
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time Frame
Baseline and month 3
Title
Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit
Description
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time Frame
Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Title
Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid
Description
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time Frame
Baseline and month 3
Title
Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit
Description
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time Frame
Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Title
Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)
Description
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.
Time Frame
Baseline and month 3
Title
Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores
Description
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.
Time Frame
Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90)
Title
Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0
Description
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:
How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now?
How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now?
Time Frame
Baseline and month 3
Title
Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0
Description
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:
How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now?
How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now?
Time Frame
Baseline and month 3
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Citations:
PubMed Identifier
28579415
Citation
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.
Results Reference
background
PubMed Identifier
27733082
Citation
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.
Results Reference
derived
Learn more about this trial
Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids
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