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

Sponsor
AbbVie (prior sponsor, Abbott) (Industry)
Overall Status
Completed
CT.gov ID
NCT01441635
Collaborator
(none)
271
10
32.3

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
271 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 8, 2011
Actual Primary Completion Date :
Nov 1, 2013
Actual Study Completion Date :
May 17, 2014

Arms and Interventions

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®
  • Outcome Measures

    Primary Outcome Measures

    1. Mean 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)]

      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

    1. 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)]

      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.

    2. 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)]

      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.

    3. 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)]

      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.

    4. 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)]

      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.

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

    6. Change in Hemoglobin Concentration From Baseline to Month 3 [Baseline and Month 3]

    7. Change From Baseline to Month 3 in Uterine Bleeding Score [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.

    8. Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding [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.

    9. Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding [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.

    10. Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 [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.

    11. Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment [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.

    12. Percent Change From Baseline to Month 3 in Uterine Volume [Baseline and month 3]

      Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.

    13. Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit [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.

    14. Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid [Baseline and month 3]

      The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.

    15. Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit [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.

    16. Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) [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.

    17. Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores [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.

    18. Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 [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: 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?

    19. Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 [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: 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?

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 49 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • AbbVie (prior sponsor, Abbott)

    Investigators

    • Study Director: AbbVie Inc., AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    AbbVie (prior sponsor, Abbott)
    ClinicalTrials.gov Identifier:
    NCT01441635
    Other Study ID Numbers:
    • M12-663
    First Posted:
    Sep 28, 2011
    Last Update Posted:
    Jul 13, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Keywords provided by AbbVie (prior sponsor, Abbott)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Overall, 271 female participants were enrolled into the study across 45 sites in the United States.
    Pre-assignment Detail Six cohorts of participants were enrolled, with 3 double-blind cohorts comparing elagolix with placebo, 2 open-label cohorts assessing add-back therapies, and 1 open-label cohort assessing the elagolix 600 mg QD dosing regimen.
    Arm/Group Title 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/Group 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.
    Period Title: Overall Study
    STARTED 32 33 16 35 18 34 30 30 16 27
    COMPLETED 26 27 13 28 16 29 24 26 14 25
    NOT COMPLETED 6 6 3 7 2 5 6 4 2 2

    Baseline Characteristics

    Arm/Group Title 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 Total
    Arm/Group 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. Total of all reporting groups
    Overall Participants 32 33 16 35 18 34 30 30 16 27 271
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    40.8
    (5.50)
    42.1
    (5.09)
    41.1
    (5.88)
    43.1
    (4.29)
    44.0
    (4.24)
    40.9
    (6.02)
    40.8
    (5.78)
    42.6
    (5.55)
    41.6
    (7.10)
    41.6
    (5.26)
    41.8
    (5.4)
    Age, Customized (Count of Participants)
    < 35 years
    7
    21.9%
    3
    9.1%
    2
    12.5%
    2
    5.7%
    0
    0%
    5
    14.7%
    4
    13.3%
    3
    10%
    3
    18.8%
    3
    11.1%
    32
    11.8%
    35 to < 40 years
    6
    18.8%
    5
    15.2%
    5
    31.3%
    5
    14.3%
    2
    11.1%
    8
    23.5%
    6
    20%
    5
    16.7%
    3
    18.8%
    6
    22.2%
    51
    18.8%
    40 to < 45 years
    8
    25%
    13
    39.4%
    2
    12.5%
    13
    37.1%
    7
    38.9%
    10
    29.4%
    11
    36.7%
    9
    30%
    3
    18.8%
    10
    37%
    86
    31.7%
    ≥ 45 years
    11
    34.4%
    12
    36.4%
    7
    43.8%
    15
    42.9%
    9
    50%
    11
    32.4%
    9
    30%
    13
    43.3%
    7
    43.8%
    8
    29.6%
    102
    37.6%
    Sex: Female, Male (Count of Participants)
    Female
    32
    100%
    33
    100%
    16
    100%
    35
    100%
    18
    100%
    34
    100%
    30
    100%
    30
    100%
    16
    100%
    27
    100%
    271
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    3.1%
    8
    24.2%
    1
    6.3%
    1
    2.9%
    1
    5.6%
    1
    2.9%
    6
    20%
    0
    0%
    2
    12.5%
    12
    44.4%
    33
    12.2%
    Not Hispanic or Latino
    31
    96.9%
    25
    75.8%
    15
    93.8%
    34
    97.1%
    17
    94.4%
    33
    97.1%
    24
    80%
    30
    100%
    14
    87.5%
    15
    55.6%
    238
    87.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    White
    5
    15.6%
    10
    30.3%
    3
    18.8%
    7
    20%
    3
    16.7%
    7
    20.6%
    5
    16.7%
    6
    20%
    6
    37.5%
    11
    40.7%
    63
    23.2%
    Black
    25
    78.1%
    23
    69.7%
    13
    81.3%
    28
    80%
    14
    77.8%
    26
    76.5%
    24
    80%
    23
    76.7%
    9
    56.3%
    15
    55.6%
    200
    73.8%
    Asian
    1
    3.1%
    0
    0%
    0
    0%
    0
    0%
    1
    5.6%
    1
    2.9%
    0
    0%
    0
    0%
    1
    6.3%
    0
    0%
    4
    1.5%
    Other
    1
    3.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3.3%
    1
    3.3%
    0
    0%
    0
    0%
    3
    1.1%
    Multirace
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3.7%
    1
    0.4%

    Outcome Measures

    1. Primary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. Last observation carried forward (LOCF) imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
    Arm/Group Title 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/Group 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.
    Measure Participants 31 31 15 32 18 33 28 30 15 26
    Baseline
    213.70
    (108.08)
    269.36
    (163.17)
    321.73
    (327.57)
    335.11
    (322.68)
    251.72
    (160.29)
    247.70
    (177.72)
    215.62
    (122.84)
    206.27
    (125.08)
    349.17
    (424.12)
    257.99
    (207.33)
    Change from Baseline
    -183.97
    (132.19)
    -184.69
    (187.05)
    -10.46
    (85.04)
    -272.97
    (271.39)
    -79.00
    (161.33)
    -192.33
    (191.51)
    -189.05
    (151.15)
    -202.57
    (127.93)
    -175.31
    (342.14)
    -216.15
    (157.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -205.9
    Confidence Interval (2-Sided) 95%
    -295.77 to -116.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 45.10
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -189.9
    Confidence Interval (2-Sided) 95%
    -278.33 to -101.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 44.36
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -138.0
    Confidence Interval (2-Sided) 95%
    -220.18 to -55.76
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 40.86
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -130.6
    Confidence Interval (2-Sided) 95%
    -206.70 to -54.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 37.68
    Estimation Comments
    2. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. Last observation carried forward (LOCF) imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the electronic diary.
    Arm/Group Title 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/Group 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.
    Measure Participants 31 31 15 32 18 33 28 30 15 26
    Mean (Standard Deviation) [percent change]
    -83.83
    (35.23)
    -71.85
    (49.20)
    -6.98
    (40.78)
    -81.03
    (55.77)
    -11.12
    (103.11)
    -79.60
    (43.63)
    -88.58
    (39.58)
    -97.31
    (12.57)
    -42.64
    (39.68)
    -85.39
    (28.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -75.60
    Confidence Interval (2-Sided) 95%
    -102.93 to -48.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 13.71
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -64.27
    Confidence Interval (2-Sided) 95%
    -91.14 to -37.39
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 13.48
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -67.67
    Confidence Interval (2-Sided) 95%
    -113.39 to -21.96
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 22.73
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS mean Difference
    Estimated Value -56.84
    Confidence Interval (2-Sided) 95%
    -73.24 to -40.45
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.12
    Estimation Comments
    3. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
    Arm/Group Title 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/Group 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.
    Measure Participants 31 31 15 33 18 33 28 30 15 26
    Number [percentage of participants]
    84
    262.5%
    74
    224.2%
    13
    81.3%
    85
    242.9%
    17
    94.4%
    85
    250%
    93
    310%
    97
    323.3%
    33
    206.3%
    85
    314.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
    Arm/Group Title 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/Group 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.
    Measure Participants 31 31 15 33 18 33 28 30 15 26
    Number [percentage of participants]
    84
    262.5%
    74
    224.2%
    13
    81.3%
    85
    242.9%
    22
    122.2%
    88
    258.8%
    93
    310%
    97
    323.3%
    47
    293.8%
    88
    325.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    5. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
    Arm/Group Title 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/Group 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.
    Measure Participants 31 31 15 33 18 33 28 30 15 26
    Number [percentage of participants]
    84
    262.5%
    74
    224.2%
    13
    81.3%
    91
    260%
    28
    155.6%
    85
    250%
    93
    310%
    97
    323.3%
    40
    250%
    88
    325.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    6. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available hemoglobin data.
    Arm/Group Title 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/Group 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.
    Measure Participants 23 24 11 27 14 28 23 25 14 21
    No Change
    0
    0%
    0
    0%
    9
    56.3%
    0
    0%
    0
    0%
    0
    0%
    4
    13.3%
    0
    0%
    0
    0%
    5
    18.5%
    Decreases from -0.5 to 0 g/dL
    9
    28.1%
    17
    51.5%
    0
    0%
    4
    11.4%
    21
    116.7%
    14
    41.2%
    4
    13.3%
    0
    0%
    21
    131.3%
    5
    18.5%
    Decreases from -1.0 to -0.5 g/dL
    4
    12.5%
    4
    12.1%
    27
    168.8%
    11
    31.4%
    14
    77.8%
    0
    0%
    4
    13.3%
    0
    0%
    7
    43.8%
    10
    37%
    Increase ≥ 0.5 g/dL
    78
    243.8%
    71
    215.2%
    18
    112.5%
    67
    191.4%
    29
    161.1%
    75
    220.6%
    83
    276.7%
    76
    253.3%
    29
    181.3%
    71
    263%
    Increase ≥ 1.0 g/dL
    61
    190.6%
    71
    215.2%
    9
    56.3%
    59
    168.6%
    29
    161.1%
    43
    126.5%
    57
    190%
    52
    173.3%
    29
    181.3%
    62
    229.6%
    7. Secondary Outcome
    Title Change in Hemoglobin Concentration From Baseline to Month 3
    Description
    Time Frame Baseline and Month 3

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available hemoglobin data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 23 24 11 27 14 28 23 25 14 21
    Mean (Standard Deviation) [g/dL]
    1.18
    (0.99)
    1.30
    (1.19)
    -0.43
    (1.28)
    1.13
    (1.29)
    0.28
    (1.33)
    0.92
    (0.81)
    1.40
    (1.18)
    1.19
    (0.85)
    0.31
    (1.20)
    1.54
    (1.81)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    0.97 to 2.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    1.00 to 2.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.39
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.024
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    0.13 to 1.75
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.9
    Confidence Interval (2-Sided) 95%
    0.28 to 1.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.30
    Estimation Comments
    8. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 30 30 15 32 17 32 26 27 15 25
    Mean (Standard Deviation) [units on a scale]
    -0.50
    (0.56)
    -0.37
    (0.46)
    -0.19
    (0.33)
    -0.52
    (0.65)
    -0.22
    (0.32)
    -0.24
    (0.47)
    -0.44
    (0.71)
    -0.53
    (0.33)
    -0.38
    (0.77)
    -0.25
    (0.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.36
    Confidence Interval (2-Sided) 95%
    -0.63 to -0.08
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.14
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.030
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.31
    Confidence Interval (2-Sided) 95%
    -0.59 to -0.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.14
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.109
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.26
    Confidence Interval (2-Sided) 95%
    -0.59 to 0.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.50
    Confidence Interval (2-Sided) 95%
    -0.80 to -0.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.15
    Estimation Comments
    9. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 30 30 15 32 17 32 26 27 15 25
    Mean (Standard Deviation) [percentage of days]
    -15.22
    (14.77)
    -11.00
    (15.52)
    -5.78
    (10.58)
    -15.82
    (17.88)
    -6.99
    (12.82)
    3.63
    (24.74)
    -15.38
    (23.21)
    -16.91
    (11.13)
    -13.95
    (23.83)
    1.73
    (26.09)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -10.29
    Confidence Interval (2-Sided) 95%
    -18.90 to -1.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.32
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.087
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -7.62
    Confidence Interval (2-Sided) 95%
    -16.36 to 1.13
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.39
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.045
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -8.81
    Confidence Interval (2-Sided) 95%
    -17.43 to -0.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.28
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -13.69
    Confidence Interval (2-Sided) 95%
    -22.06 to -5.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.14
    Estimation Comments
    10. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 30 30 15 32 17 32 26 27 15 25
    Mean (Standard Deviation) [percentage of days]
    -7.22
    (9.27)
    -5.00
    (7.87)
    -4.00
    (5.37)
    -7.03
    (10.89)
    -3.08
    (5.88)
    -7.92
    (6.43)
    -6.15
    (8.47)
    -8.02
    (5.41)
    -3.31
    (10.40)
    -6.80
    (10.69)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -5.51
    Confidence Interval (2-Sided) 95%
    -9.56 to -1.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.03
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -4.95
    Confidence Interval (2-Sided) 95%
    -9.11 to -0.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.08
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.194
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -3.63
    Confidence Interval (2-Sided) 95%
    -9.18 to 1.91
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.75
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments ANCOVA model with treatment as a factor and baseline as a covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -7.20
    Confidence Interval (2-Sided) 95%
    -11.33 to -3.07
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.04
    Estimation Comments
    11. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 30 30 15 32 17 32 26 27 15 26
    Any bleeding
    37
    115.6%
    57
    172.7%
    93
    581.3%
    47
    134.3%
    94
    522.2%
    78
    229.4%
    27
    90%
    26
    86.7%
    80
    500%
    69
    255.6%
    Moderate to Very Heavy Bleeding
    27
    84.4%
    40
    121.2%
    87
    543.8%
    28
    80%
    82
    455.6%
    31
    91.2%
    15
    50%
    7
    23.3%
    73
    456.3%
    35
    129.6%
    12. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants including participants with less than 56 days of treatment who bled but excluded those who did not bleed.
    Arm/Group Title 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/Group 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.
    Measure Participants 30 29 15 32 18 32 26 29 16 26
    Suppression of bleeding
    66
    206.3%
    45
    136.4%
    0
    0%
    66
    188.6%
    0
    0%
    31
    91.2%
    77
    256.7%
    79
    263.3%
    0
    0%
    32
    118.5%
    Amenorrhea
    60
    187.5%
    31
    93.9%
    0
    0%
    44
    125.7%
    0
    0%
    19
    55.9%
    73
    243.3%
    66
    220%
    0
    0%
    19
    70.4%
    13. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 22 20 9 22 12 22 20 20 12 11
    Mean (Standard Deviation) [percent change]
    -21.01
    (26.79)
    -21.37
    (24.84)
    18.72
    (15.59)
    -21.68
    (29.80)
    -8.62
    (20.58)
    -17.43
    (19.51)
    -27.99
    (23.34)
    -33.25
    (16.55)
    -1.92
    (17.52)
    -10.06
    (30.93)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Kruskal-Wallis
    Comments One-way Kruskal-Wallis test with treatment as a factor.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Kruskal-Wallis
    Comments One-way Kruskal-Wallis test with treatment as a factor.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.052
    Comments
    Method Kruskal-Wallis
    Comments One-way Kruskal-Wallis test with treatment as a factor.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Kruskal-Wallis
    Comments One-way Kruskal-Wallis test with treatment as a factor.
    14. Secondary Outcome
    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.

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 30 30 15 31 18 33 27 29 15 24
    Number [percentage of participants]
    53
    165.6%
    43
    130.3%
    7
    43.8%
    48
    137.1%
    11
    61.1%
    42
    123.5%
    56
    186.7%
    69
    230%
    7
    43.8%
    25
    92.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.016
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    15. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available fibroid volume data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 19 18 9 22 12 22 18 20 12 10
    Mean (Standard Deviation) [percent change]
    14.23
    (187.83)
    -22.19
    (51.14)
    -7.26
    (36.35)
    -38.52
    (41.72)
    -2.05
    (71.83)
    -25.77
    (46.64)
    -16.60
    (39.61)
    -35.79
    (24.49)
    6.70
    (45.42)
    -4.94
    (100.68)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.161
    Comments
    Method Kruskal-Wallis
    Comments One-way Kruskal-Wallis test with treatment as a factor
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.173
    Comments
    Method Kruskal-Wallis
    Comments One-way Kruskal-Wallis test with treatment as a factor.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.072
    Comments
    Method Kruskal-Wallis
    Comments One-way Kruskal-Wallis test with treatment as a factor.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Kruskal-Wallis
    Comments One-way Kruskal-Wallis test with treatment as a factor.
    16. Secondary Outcome
    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.

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 28 29 15 31 17 33 25 29 15 21
    Number [percentage of participants]
    57
    178.1%
    52
    157.6%
    33
    206.3%
    68
    194.3%
    35
    194.4%
    58
    170.6%
    60
    200%
    55
    183.3%
    27
    168.8%
    48
    177.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.203
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.342
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.038
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.111
    Comments
    Method Fisher Exact
    Comments
    17. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available UFS-QoL data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 23 21 9 26 13 22 20 25 13 14
    Symptom severity
    -39.0
    (24.70)
    -33.2
    (28.17)
    -19.6
    (32.80)
    -31.6
    (28.87)
    -21.4
    (20.63)
    -20.3
    (25.35)
    -36.4
    (24.74)
    -44.1
    (22.12)
    -12.0
    (22.49)
    -39.1
    (24.09)
    HRQL total
    35.3
    (21.87)
    29.1
    (30.96)
    16.3
    (30.43)
    36.0
    (27.91)
    18.3
    (36.66)
    28.6
    (24.12)
    29.9
    (30.72)
    33.5
    (29.42)
    11.0
    (20.90)
    33.1
    (30.34)
    18. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 18 18 9 18 11 22 16 20 9 11
    Pelvic pain
    -1.0
    (2.27)
    -0.2
    (2.39)
    -0.3
    (1.45)
    -0.6
    (1.75)
    -1.4
    (1.62)
    -1.1
    (1.35)
    -0.9
    (2.15)
    -1.0
    (1.75)
    -1.2
    (1.73)
    -2.4
    (3.00)
    Fatigue
    -0.5
    (1.26)
    -0.0
    (2.23)
    -0.6
    (1.45)
    -0.6
    (1.29)
    -0.5
    (1.69)
    -1.2
    (1.92)
    -1.0
    (2.57)
    -1.5
    (1.16)
    -0.5
    (2.88)
    -2.1
    (3.11)
    Menstrual cramping
    -1.2
    (1.31)
    -0.7
    (2.51)
    -0.5
    (1.55)
    -0.9
    (1.16)
    -1.2
    (0.80)
    -0.9
    (1.25)
    -1.1
    (1.35)
    -1.2
    (1.09)
    -1.0
    (2.33)
    -1.3
    (2.15)
    Impact of uterine fibroids
    -1.1
    (1.18)
    -0.4
    (1.86)
    -0.8
    (1.40)
    -1.0
    (1.37)
    -1.0
    (1.81)
    -0.9
    (1.62)
    -1.7
    (2.41)
    -1.3
    (1.11)
    -1.0
    (2.18)
    -3.1
    (2.78)
    19. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 23 21 9 9 6 22 20 25 13 14
    Likelihood of having myomectomy
    -1.2
    (3.68)
    -3.1
    (4.52)
    1.0
    (2.12)
    -1.8
    (4.70)
    2.3
    (5.35)
    -1.4
    (4.34)
    -1.7
    (4.18)
    -0.6
    (5.10)
    0.4
    (4.16)
    0.1
    (2.63)
    Likelihood of having hysterectomy
    0.0
    (4.04)
    -1.9
    (4.19)
    2.0
    (3.64)
    -0.8
    (4.91)
    -0.3
    (0.52)
    -0.7
    (3.10)
    -0.8
    (4.42)
    0.2
    (3.65)
    0.0
    (1.96)
    -1.5
    (3.92)
    20. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
    Arm/Group Title 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/Group 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.
    Measure Participants 23 21 9 9 7 22 20 24 13 14
    Likelihood to recommend myomectomy
    -0.9
    (2.86)
    -1.3
    (3.31)
    -2.7
    (3.53)
    -0.8
    (1.76)
    0.7
    (1.11)
    -0.6
    (2.97)
    -1.3
    (3.62)
    -1.2
    (3.59)
    0.0
    (3.25)
    0.0
    (3.94)
    Likelihood to recommend hysterectomy
    -0.8
    (3.34)
    -1.8
    (4.37)
    -0.2
    (3.15)
    -2.2
    (2.82)
    0.4
    (1.62)
    -1.4
    (3.08)
    -2.3
    (3.99)
    -1.5
    (3.96)
    -0.6
    (2.81)
    -2.8
    (2.98)

    Adverse Events

    Time Frame From the date of the first dose of study drug through up to 30 days after the last dose of study drug, up to 4 months.
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1 Placebo Cohort 1 Elagolix 200 mg BID Cohort 2 Placebo Cohort 2 Elagolix 300 mg BID Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 4 Placebo Cohort 4 Elagolix 100 mg BID Cohort 4 Golix 400 mg QD Cohort 5 Elagolix 600 mg QD Cohort 6 Elagolix 300 mg BID + CEP
    Arm/Group Description Participants received placebo to elagolix twice a day for 3 months. Participants received elagolix 200 mg twice a day for 3 months. Participants received placebo to elagolix BID for 3 months. Participants received elagolix 300 mg 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 placebo to elagolix BID for 3 months. Participants received elagolix 100 mg twice a day (BID) for 3 months. Participants received elagolix 400 mg once a day (QD) for 3 months. Participants received elagolix 600 mg once a day 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.
    All Cause Mortality
    Cohort 1 Placebo Cohort 1 Elagolix 200 mg BID Cohort 2 Placebo Cohort 2 Elagolix 300 mg BID Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 4 Placebo Cohort 4 Elagolix 100 mg BID Cohort 4 Golix 400 mg QD Cohort 5 Elagolix 600 mg QD Cohort 6 Elagolix 300 mg BID + CEP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 0/32 (0%) 0/30 (0%) 0/27 (0%)
    Serious Adverse Events
    Cohort 1 Placebo Cohort 1 Elagolix 200 mg BID Cohort 2 Placebo Cohort 2 Elagolix 300 mg BID Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 4 Placebo Cohort 4 Elagolix 100 mg BID Cohort 4 Golix 400 mg QD Cohort 5 Elagolix 600 mg QD Cohort 6 Elagolix 300 mg BID + CEP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/18 (5.6%) 0/35 (0%) 0/16 (0%) 1/30 (3.3%) 0/34 (0%) 2/16 (12.5%) 2/33 (6.1%) 0/32 (0%) 2/30 (6.7%) 0/27 (0%)
    Blood and lymphatic system disorders
    ANAEMIA 1/18 (5.6%) 1 0/35 (0%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 2/16 (12.5%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    Gastrointestinal disorders
    PANCREATITIS 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 0/32 (0%) 1/30 (3.3%) 1 0/27 (0%) 1
    General disorders
    NECROSIS 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 1/33 (3%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Hepatobiliary disorders
    CHOLECYSTITIS 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 1/33 (3%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Metabolism and nutrition disorders
    HYPOVOLAEMIA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    UTERINE LEIOMYOMA 0/18 (0%) 0/35 (0%) 0/16 (0%) 1/30 (3.3%) 1 0/34 (0%) 1 0/16 (0%) 1 1/33 (3%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Reproductive system and breast disorders
    UTERINE HAEMORRHAGE 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 1/33 (3%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Surgical and medical procedures
    ABORTION INDUCED 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 0/32 (0%) 1/30 (3.3%) 1 0/27 (0%) 1
    Other (Not Including Serious) Adverse Events
    Cohort 1 Placebo Cohort 1 Elagolix 200 mg BID Cohort 2 Placebo Cohort 2 Elagolix 300 mg BID Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 4 Placebo Cohort 4 Elagolix 100 mg BID Cohort 4 Golix 400 mg QD Cohort 5 Elagolix 600 mg QD Cohort 6 Elagolix 300 mg BID + CEP
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/18 (44.4%) 26/35 (74.3%) 10/16 (62.5%) 20/30 (66.7%) 20/34 (58.8%) 9/16 (56.3%) 20/33 (60.6%) 24/32 (75%) 22/30 (73.3%) 11/27 (40.7%)
    Blood and lymphatic system disorders
    ANAEMIA 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 1/30 (3.3%) 1 0/34 (0%) 1 1/16 (6.3%) 1 2/33 (6.1%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    LEUKOCYTOSIS 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Gastrointestinal disorders
    ABDOMINAL PAIN 1/18 (5.6%) 1 2/35 (5.7%) 2 0/16 (0%) 2 3/30 (10%) 5 0/34 (0%) 5 0/16 (0%) 5 0/33 (0%) 5 0/32 (0%) 5 2/30 (6.7%) 2 4/27 (14.8%) 5
    NAUSEA 0/18 (0%) 3/35 (8.6%) 4 2/16 (12.5%) 2 2/30 (6.7%) 2 0/34 (0%) 2 1/16 (6.3%) 1 0/33 (0%) 1 5/32 (15.6%) 5 9/30 (30%) 9 4/27 (14.8%) 4
    ABDOMINAL DISCOMFORT 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 1/30 (3.3%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    ABDOMINAL DISTENSION 0/18 (0%) 0/35 (0%) 0/16 (0%) 2/30 (6.7%) 2 0/34 (0%) 2 1/16 (6.3%) 1 1/33 (3%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    ABDOMINAL PAIN LOWER 0/18 (0%) 0/35 (0%) 0/16 (0%) 2/30 (6.7%) 2 0/34 (0%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    CONSTIPATION 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 2/16 (12.5%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    DIARRHOEA 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 1/30 (3.3%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 3/30 (10%) 3 3/27 (11.1%) 3
    GASTROOESOPHAGEAL REFLUX DISEASE 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 2/16 (12.5%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    VOMITING 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 1/30 (3.3%) 2 0/34 (0%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 2/30 (6.7%) 2 0/27 (0%) 2
    DRY MOUTH 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 2/32 (6.3%) 2 0/30 (0%) 2 0/27 (0%) 2
    PEPTIC ULCER 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    General disorders
    FATIGUE 1/18 (5.6%) 1 2/35 (5.7%) 2 0/16 (0%) 2 0/30 (0%) 2 4/34 (11.8%) 4 0/16 (0%) 4 1/33 (3%) 1 4/32 (12.5%) 4 2/30 (6.7%) 2 0/27 (0%) 2
    OEDEMA PERIPHERAL 1/18 (5.6%) 1 0/35 (0%) 1 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 2/32 (6.3%) 2 0/30 (0%) 2 0/27 (0%) 2
    CHILLS 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    INFLUENZA LIKE ILLNESS 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    IRRITABILITY 0/18 (0%) 0/35 (0%) 2/16 (12.5%) 2 0/30 (0%) 2 0/34 (0%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    MALAISE 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    VESSEL PUNCTURE SITE PAIN 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Immune system disorders
    HYPERSENSITIVITY 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 0/32 (0%) 0/30 (0%) 2/27 (7.4%) 2
    Infections and infestations
    BRONCHITIS 1/18 (5.6%) 1 0/35 (0%) 1 0/16 (0%) 1 0/30 (0%) 1 2/34 (5.9%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    VAGINITIS BACTERIAL 1/18 (5.6%) 1 1/35 (2.9%) 1 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    FUNGAL INFECTION 0/18 (0%) 0/35 (0%) 2/16 (12.5%) 2 0/30 (0%) 2 0/34 (0%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    VULVOVAGINITIS 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    FURUNCLE 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    INFECTED BITES 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    NASOPHARYNGITIS 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 2/32 (6.3%) 2 0/30 (0%) 2 0/27 (0%) 2
    UPPER RESPIRATORY TRACT INFECTION 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 2/32 (6.3%) 2 2/30 (6.7%) 2 0/27 (0%) 2
    URINARY TRACT INFECTION 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 1/33 (3%) 1 3/32 (9.4%) 3 0/30 (0%) 3 0/27 (0%) 3
    Injury, poisoning and procedural complications
    LACERATION 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 0/32 (0%) 2/30 (6.7%) 2 0/27 (0%) 2
    Investigations
    BLOOD PRESSURE INCREASED 1/18 (5.6%) 1 0/35 (0%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 2/27 (7.4%) 2
    WEIGHT INCREASED 1/18 (5.6%) 1 0/35 (0%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    BLOOD GLUCOSE INCREASED 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    ALANINE AMINOTRANSFERASE INCREASED 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 1/32 (3.1%) 1 0/30 (0%) 1 0/27 (0%) 1
    ASPARTATE AMINOTRANSFERASE INCREASED 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Metabolism and nutrition disorders
    DECREASED APPETITE 0/18 (0%) 2/35 (5.7%) 2 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    DIABETES MELLITUS 1/18 (5.6%) 1 1/35 (2.9%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Musculoskeletal and connective tissue disorders
    BACK PAIN 1/18 (5.6%) 1 3/35 (8.6%) 4 0/16 (0%) 4 2/30 (6.7%) 3 0/34 (0%) 3 1/16 (6.3%) 1 1/33 (3%) 1 3/32 (9.4%) 3 5/30 (16.7%) 5 0/27 (0%) 5
    MUSCLE SPASMS 1/18 (5.6%) 1 0/35 (0%) 1 1/16 (6.3%) 1 0/30 (0%) 1 3/34 (8.8%) 3 0/16 (0%) 3 0/33 (0%) 3 0/32 (0%) 3 2/30 (6.7%) 2 0/27 (0%) 2
    PAIN IN EXTREMITY 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 2/34 (5.9%) 3 0/16 (0%) 3 0/33 (0%) 3 0/32 (0%) 3 0/30 (0%) 3 0/27 (0%) 3
    ARTHRALGIA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 3/33 (9.1%) 3 1/32 (3.1%) 1 2/30 (6.7%) 3 0/27 (0%) 3
    OSTEOPENIA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 0/33 (0%) 2/32 (6.3%) 2 0/30 (0%) 2 0/27 (0%) 2
    Nervous system disorders
    DIZZINESS 0/18 (0%) 2/35 (5.7%) 2 2/16 (12.5%) 2 3/30 (10%) 3 3/34 (8.8%) 3 0/16 (0%) 3 1/33 (3%) 1 3/32 (9.4%) 3 6/30 (20%) 6 0/27 (0%) 6
    HEADACHE 0/18 (0%) 3/35 (8.6%) 3 3/16 (18.8%) 3 6/30 (20%) 6 5/34 (14.7%) 5 0/16 (0%) 5 3/33 (9.1%) 3 4/32 (12.5%) 4 9/30 (30%) 11 2/27 (7.4%) 2
    MIGRAINE 1/18 (5.6%) 1 0/35 (0%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    BALANCE DISORDER 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    LETHARGY 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Psychiatric disorders
    DEPRESSION 2/18 (11.1%) 2 1/35 (2.9%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    MOOD SWINGS 1/18 (5.6%) 1 2/35 (5.7%) 3 0/16 (0%) 3 0/30 (0%) 3 0/34 (0%) 3 0/16 (0%) 3 0/33 (0%) 3 0/32 (0%) 3 0/30 (0%) 3 0/27 (0%) 3
    LIBIDO DECREASED 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 2/34 (5.9%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    ANXIETY 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 2/33 (6.1%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    INSOMNIA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 2/33 (6.1%) 2 1/32 (3.1%) 1 0/30 (0%) 1 0/27 (0%) 1
    Renal and urinary disorders
    NEPHROLITHIASIS 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    POLLAKIURIA 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    URINARY INCONTINENCE 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Reproductive system and breast disorders
    DYSMENORRHOEA 1/18 (5.6%) 1 0/35 (0%) 1 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 1/16 (6.3%) 1 0/33 (0%) 1 1/32 (3.1%) 1 0/30 (0%) 1 2/27 (7.4%) 2
    MENORRHAGIA 1/18 (5.6%) 1 2/35 (5.7%) 3 0/16 (0%) 3 0/30 (0%) 3 0/34 (0%) 3 0/16 (0%) 3 0/33 (0%) 3 0/32 (0%) 3 0/30 (0%) 3 0/27 (0%) 3
    PELVIC PAIN 0/18 (0%) 2/35 (5.7%) 2 0/16 (0%) 2 0/30 (0%) 2 0/34 (0%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    VULVOVAGINAL DRYNESS 0/18 (0%) 2/35 (5.7%) 2 0/16 (0%) 2 0/30 (0%) 2 0/34 (0%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    AMENORRHOEA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 2/34 (5.9%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    BREAST CYST 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 2/34 (5.9%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    METRORRHAGIA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 2/34 (5.9%) 2 0/16 (0%) 2 0/33 (0%) 2 0/32 (0%) 2 0/30 (0%) 2 0/27 (0%) 2
    DYSPAREUNIA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    OVARIAN CYST 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 0/16 (0%) 2/33 (6.1%) 2 1/32 (3.1%) 1 0/30 (0%) 1 0/27 (0%) 1
    Respiratory, thoracic and mediastinal disorders
    ASTHMA 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    DYSPNOEA 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Skin and subcutaneous tissue disorders
    ACNE 1/18 (5.6%) 1 0/35 (0%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 1/33 (3%) 2 2/32 (6.3%) 2 0/30 (0%) 2 0/27 (0%) 2
    NIGHT SWEATS 0/18 (0%) 3/35 (8.6%) 3 1/16 (6.3%) 1 1/30 (3.3%) 1 0/34 (0%) 1 0/16 (0%) 1 1/33 (3%) 1 2/32 (6.3%) 3 0/30 (0%) 3 0/27 (0%) 3
    RASH GENERALISED 1/18 (5.6%) 1 0/35 (0%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    RASH MACULAR 1/18 (5.6%) 1 0/35 (0%) 1 0/16 (0%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    DRY SKIN 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    HYPERHIDROSIS 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    CHLOASMA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    URTICARIA 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    Vascular disorders
    HOT FLUSH 1/18 (5.6%) 1 19/35 (54.3%) 20 3/16 (18.8%) 3 15/30 (50%) 15 9/34 (26.5%) 9 2/16 (12.5%) 2 15/33 (45.5%) 16 20/32 (62.5%) 21 15/30 (50%) 15 5/27 (18.5%) 5
    SPIDER VEIN 0/18 (0%) 0/35 (0%) 1/16 (6.3%) 1 0/30 (0%) 1 0/34 (0%) 1 0/16 (0%) 1 0/33 (0%) 1 0/32 (0%) 1 0/30 (0%) 1 0/27 (0%) 1
    HYPERTENSION 0/18 (0%) 0/35 (0%) 0/16 (0%) 0/30 (0%) 0/34 (0%) 1/16 (6.3%) 1 0/33 (0%) 1 0/32 (0%) 1 3/30 (10%) 3 0/27 (0%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.

    Results Point of Contact

    Name/Title Global Medical Services
    Organization AbbVie (prior sponsor, Abbott)
    Phone 800-633-9110
    Email
    Responsible Party:
    AbbVie (prior sponsor, Abbott)
    ClinicalTrials.gov Identifier:
    NCT01441635
    Other Study ID Numbers:
    • M12-663
    First Posted:
    Sep 28, 2011
    Last Update Posted:
    Jul 13, 2021
    Last Verified:
    Jul 1, 2021