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Safety and Efficacy in Premenopausal Women With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF)

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT01817530
Collaborator
(none)
571
Enrollment
8
Arms
31.8
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This is a Phase 2b randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of elagolix alone and in combination with add-back therapy versus placebo on heavy menstrual bleeding in premenopausal women 18 to 51 years of age with uterine fibroids.

Condition or Disease Intervention/Treatment Phase
  • Other: Elagolix placebo
  • Drug: Elagolix
  • Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate
  • Drug: 1 mg estradiol / 0.5 mg norethindrone acetate
  • Drug: E2/NETA placebo
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
571 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Actual Study Start Date :
Apr 8, 2013
Actual Primary Completion Date :
Jun 1, 2015
Actual Study Completion Date :
Dec 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Cohort 1: Placebo

Placebo for elagolix and placebo for E2/NETA twice daily (BID)

Other: Elagolix placebo
oral coated tablet

Drug: E2/NETA placebo
oral hard capsule
Experimental: Cohort 1: Elagolix 300 mg BID

Elagolix 300 mg BID alone

Drug: Elagolix
oral coated tablet
Other Names:
  • ABT-620

    • Drug: E2/NETA placebo
    oral hard capsule
    Experimental: Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD

    Elagolix 300 mg BID plus low-dose (LD) E2/NETA once daily (QD)

    Drug: Elagolix
    oral coated tablet
    Other Names:
  • ABT-620

    • Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate
    oral hard capsule
    Other Names:
  • Activelle, Activella, low dose (LD) E2/NETA

    		•
    Experimental: Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD

    Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD

    Drug: Elagolix
    oral coated tablet
    Other Names:
  • ABT-620

    • Drug: 1 mg estradiol / 0.5 mg norethindrone acetate
    oral hard capsule
    Other Names:
  • Activelle
  • Activella
  • standard dose (SD) E2/NETA

    		•
    Placebo Comparator: Cohort 2: Placebo

    Placebo for elagolix and E2/NETA QD

    Other: Elagolix placebo
    oral coated tablet

    Drug: E2/NETA placebo
    oral hard capsule
    Experimental: Cohort 2: Elagolix 600 mg QD

    Elagolix 600 mg QD alone

    Drug: Elagolix
    oral coated tablet
    Other Names:
  • ABT-620

    • Drug: E2/NETA placebo
    oral hard capsule
    Experimental: Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD

    Elagolix 600 mg QD plus LD E2/NETA QD

    Drug: Elagolix
    oral coated tablet
    Other Names:
  • ABT-620

    • Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate
    oral hard capsule
    Other Names:
  • Activelle, Activella, low dose (LD) E2/NETA

    		•
    Experimental: Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD

    Elagolix 600 mg QD plus SD E2/NETA QD

    Drug: Elagolix
    oral coated tablet
    Other Names:
  • ABT-620

    • Drug: 1 mg estradiol / 0.5 mg norethindrone acetate
    oral hard capsule
    Other Names:
  • Activelle
  • Activella
  • standard dose (SD) E2/NETA

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month [Baseline, Final Month (last 28 days of treatment)]

      The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL Volume of < 80 mL at the Final Month and a ≥50% Reduction in MBL Volume from Baseline to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.

    Secondary Outcome Measures

    1. Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment [Baseline, second last 28 days of treatment (last 56 to 29 days of treatment)]

      The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 56 to 29 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.

    2. Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment [Baseline, third last 28 days of treatment (last 84 to 57 days of treatment)]

      The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 84 to 57 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.

    3. Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month [Final Month (last 28 days of treatment)]

      Percentage of participants who achieved an MBL volume of < 80 mL at the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.

    4. Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month [Baseline, Final Month (last 28 days of treatment)]

      Percentage of participants with a >= 50% reduction from baseline in MBL to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.

    5. Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment [Last 56 days of treatment (after 10 days from first dose date)]

      Amenorrhea is defined as having 0 days of bleeding or spotting based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding or spotting, based on imputed electronic diary data during the last 56 days of treatment. Participants needed to have at least 66 days on treatment.

    6. Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment [Last 56 days of treatment (after 10 days from first dose date)]

      Suppression of bleeding is defined as having 0 days of bleeding based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding (spotting is allowed) based on imputed electronic diary data during the last 56 days of treatment.

    7. Mean Change in the Number of Bleeding Days From Baseline to Month 6 [Baseline, Month 6]

      The number of days with any bleeding including spotting was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.

    8. Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 [Baseline, Month 6]

      The number of days with heavy bleeding (either heavy or very heavy/gushing bleeding) was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.

    9. Change in Bleeding Severity Scores From Baseline at the Final Month [Baseline, Final Month (last 28 days of treatment)]

      The average bleeding score was calculated for each 28-day interval starting on Day 29 using data collected on daily bleeding diary using the Mansfield-Voda-Jorgenson (MVJ) Menstrual Bleeding Scale (1=spotting, 2 = very light bleeding, 3 = light bleeding, 4 = moderate bleeding, 5 = heavy bleeding, 6 = very heavy/gushing bleeding). Baseline is defined as the last 28 days prior to the first day of study drug.

    10. Mean Change in Hemoglobin Concentration From Baseline to Final Visit [Baseline, Final Visit during treatment period (Month 6 or early termination)]

      Baseline is defined as the last measurement prior to the first dose of study drug.

    11. Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit [Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)]

      Volume of the total fibroid volume (3 largest fibroids), as measured by transvaginal ultrasound, or transabdominal ultrasound.

    12. Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit [Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)]

      Volume of the largest fibroid (primary fibroid), as measured by transvaginal ultrasound, or transabdominal ultrasound.

    13. Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit [Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)]

      Uterine volume, as measured by transvaginal ultrasound or transabdominal ultrasound.

    14. Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit [Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)]

      Total fibroid volume (3 largest fibroids) was measured by transvaginal ultrasound, or transabdominal ultrasound.

    15. Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit [Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)]

      Volume of the largest fibroid (primary fibroid) was measured by transvaginal ultrasound or transabdominal ultrasound.

    16. Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit [Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)]

      Uterine volume was measured by transvaginal ultrasound or transabdominal ultrasound.

    17. Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire [Baseline, Days 1-28, Days 29-56, Days 57-84, Days 85-112, Days 113-140, Days 141-168, Final Month of treatment, Post-treatment (PT) Days 1-28, PT Days 29-56, PT Days 57-84, PT Days 85-112, PT Days 113-140, PT Days 141-168]

      The NBUFSQ (8 items) is a brief patient-reported daily diary that assesses non-bleeding symptoms experienced by women with uterine fibroids. It includes 6 items, asking women to rate their symptoms (abdominal/pelvic pain, pressure, and cramping, back pain, bloating, and urinary problems) in the past 24 hours using an 11-point numeric response scale that ranges from 0 (i.e., no symptom) to 10 (i.e., worst possible symptom) and 2 items to address urinary frequency during the daytime and at night. Data presented in the sum of scores to the 6 symptom questions, ranging from 0 (no symptoms) to 60 (worst possible symptoms). Baseline is defined as the last 28 days prior to the first day of study drug. Final Month is defined as the last 28 days prior to and including the last dose date of study drug.

    18. Percentage of Participants Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids [Month 6]

      The percentage of participants who successfully avoided surgical or invasive procedures for Uterine Fibroids was assessed.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 51 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Subject is pre-menopausal female 18 to 51 years of age at Screening.

    • Subject has diagnosis of uterine fibroids documented by a Pelvic Ultrasound.

    • Subject has heavy uterine bleeding associated with uterine fibroids.

    Exclusion Criteria:

    • Subject has had a myomectomy, uterine artery embolization or high intensity focused ultrasound for fibroid destruction within 6 months prior to Screening or endometrial ablation within 5 years prior to Screening.

    • 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, schizophrenia, bipolar disorder), or neurologic diseases or any uncontrolled medical illness such as uncontrolled type 2 diabetes. Subject has any history of attempted suicide.

    • Subject has a history of clinically significant condition(s) including but not limited to: * Symptomatic Endometriosis * Epilepsy or seizures * Type 1 diabetes * Chronic kidney disease * Any cancer (except treated 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

    Investigators

    • Study Director: Charlotte Owens, MD, AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT01817530
    Other Study ID Numbers:
    • M12-813
    • 2013-000082-37
    First Posted:
    Mar 25, 2013
    Last Update Posted:
    Jul 21, 2020
    Last Verified:
    Jun 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by AbbVie
    Uterine Fibroids
    Leiomyomata
    Elagolix
    Menorrhagia
    Elagolix sodium
    Heavy Uterine Bleeding
    ABT-620
    Additional relevant MeSH terms:
    Leiomyoma
    Myofibroma
    Uterine Hemorrhage
    Menorrhagia
    Hemorrhage
    Estradiol 17 beta-cypionate
    Estradiol 3-benzoate
    Norethindrone
    Norethindrone Acetate
    Estradiol
    Polyestradiol phosphate

    Study Results

    Participant Flow

    Recruitment Details Overall, 571 female participants were enrolled into the study across 86 sites (5 sites in the UK, 4 in Chile, 2 in Canada, 4 in Puerto Rico, and 71 in the US).
    Pre-assignment Detail Four participants were randomized in error; they were not dosed and were excluded from all analyses including demographic summaries.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix twice daily (BID) and placebo for E2/NETA once daily (QD) Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus low-dose (LD) E2/NETA QD Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Period Title: Overall Study
    STARTED 65 65 64 65 78 77 76 77
    COMPLETED 50 52 53 52 67 58 53 53
    NOT COMPLETED 15 13 11 13 11 19 23 24

    Baseline Characteristics

    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD Total
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD Total of all reporting groups
    Overall Participants 65 65 64 65 78 77 76 77 567
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    42.5
    (6.14)
    42.0
    (4.76)
    43.0
    (5.02)
    43.8
    (4.66)
    42.3
    (4.78)
    42.1
    (4.93)
    41.1
    (5.74)
    42.2
    (5.40)
    42.3
    (5.22)
    Sex: Female, Male (Count of Participants)
    Female
    65
    100%
    65
    100%
    64
    100%
    65
    100%
    78
    100%
    77
    100%
    76
    100%
    77
    100%
    567
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month
    Description The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL Volume of < 80 mL at the Final Month and a ≥50% Reduction in MBL Volume from Baseline to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.
    Time Frame Baseline, Final Month (last 28 days of treatment)

    Outcome Measure Data

    Analysis Population Description
    Modified Intent-to-Treat (ITT): randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with < 28 days of treatment.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 64 62 61 62 76 71 73 76
    Number [percentage of participants]
    26.56
    40.9%
    91.94
    141.4%
    85.25
    133.2%
    79.03
    121.6%
    31.58
    40.5%
    90.14
    117.1%
    72.6
    95.5%
    81.58
    105.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 32.51
    Confidence Interval (2-Sided) 95%
    11.12 to 95.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 16.66
    Confidence Interval (2-Sided) 95%
    6.72 to 41.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 11.13
    Confidence Interval (2-Sided) 95%
    4.79 to 25.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 19.62
    Confidence Interval (2-Sided) 95%
    7.81 to 49.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.02
    Confidence Interval (2-Sided) 95%
    2.95 to 12.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 10.34
    Confidence Interval (2-Sided) 95%
    4.79 to 22.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    2. Secondary Outcome
    Title Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment
    Description The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 56 to 29 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.
    Time Frame Baseline, second last 28 days of treatment (last 56 to 29 days of treatment)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with < 56 days of treatment.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 62 58 59 60 76 68 64 70
    Number [percentage of participants]
    11.29
    17.4%
    94.83
    145.9%
    88.14
    137.7%
    85.00
    130.8%
    18.42
    23.6%
    85.29
    110.8%
    67.19
    88.4%
    77.14
    100.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 156.17
    Confidence Interval (2-Sided) 95%
    38.04 to 641.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 66.07
    Confidence Interval (2-Sided) 95%
    21.1 to 206.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 52.15
    Confidence Interval (2-Sided) 95%
    17.42 to 156.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 25.45
    Confidence Interval (2-Sided) 95%
    10.45 to 61.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 9.65
    Confidence Interval (2-Sided) 95%
    4.38 to 21.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 16.17
    Confidence Interval (2-Sided) 95%
    7.13 to 36.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    3. Secondary Outcome
    Title Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment
    Description The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 84 to 57 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.
    Time Frame Baseline, third last 28 days of treatment (last 84 to 57 days of treatment)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with < 84 days of treatment.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 61 56 57 58 74 66 62 65
    Number [percentage of participants]
    19.67
    30.3%
    96.43
    148.4%
    89.47
    139.8%
    79.31
    122%
    21.62
    27.7%
    86.36
    112.2%
    74.19
    97.6%
    72.31
    93.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 123.14
    Confidence Interval (2-Sided) 95%
    25.93 to 584.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 40.56
    Confidence Interval (2-Sided) 95%
    13.59 to 121.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 19.01
    Confidence Interval (2-Sided) 95%
    7.44 to 48.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 22.77
    Confidence Interval (2-Sided) 95%
    9.29 to 55.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 10.89
    Confidence Interval (2-Sided) 95%
    4.88 to 24.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 9.72
    Confidence Interval (2-Sided) 95%
    4.46 to 21.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    4. Secondary Outcome
    Title Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month
    Description Percentage of participants who achieved an MBL volume of < 80 mL at the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.
    Time Frame Final Month (last 28 days of treatment)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with < 28 days of treatment.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 64 62 61 62 76 71 73 76
    Number [percentage of participants]
    32.81
    50.5%
    91.94
    141.4%
    88.52
    138.3%
    79.03
    121.6%
    36.84
    47.2%
    91.55
    118.9%
    72.6
    95.5%
    85.53
    111.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 24.73
    Confidence Interval (2-Sided) 95%
    8.57 to 71.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 17.21
    Confidence Interval (2-Sided) 95%
    6.57 to 45.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 8.69
    Confidence Interval (2-Sided) 95%
    3.79 to 19.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 18.67
    Confidence Interval (2-Sided) 95%
    7.11 to 49.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.94
    Confidence Interval (2-Sided) 95%
    2.43 to 10.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Regression, Logistic
    Comments P value is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 11.76
    Confidence Interval (2-Sided) 95%
    5.17 to 26.79
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    5. Secondary Outcome
    Title Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month
    Description Percentage of participants with a >= 50% reduction from baseline in MBL to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.
    Time Frame Baseline, Final Month (last 28 days of treatment)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with < 28 days of treatment.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 64 62 61 62 76 71 73 76
    Number [percentage of participants]
    31.25
    48.1%
    93.55
    143.9%
    86.89
    135.8%
    82.26
    126.6%
    35.53
    45.6%
    90.14
    117.1%
    79.45
    104.5%
    85.53
    111.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 31.48
    Confidence Interval (2-Sided) 95%
    10.02 to 98.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 14.39
    Confidence Interval (2-Sided) 95%
    5.77 to 35.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 9.82
    Confidence Interval (2-Sided) 95%
    4.23 to 22.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 16.58
    Confidence Interval (2-Sided) 95%
    6.66 to 41.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 7.02
    Confidence Interval (2-Sided) 95%
    3.36 to 14.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 10.73
    Confidence Interval (2-Sided) 95%
    4.85 to 23.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a chi-square test.
    Method Chi-squared
    Comments
    6. Secondary Outcome
    Title Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment
    Description Amenorrhea is defined as having 0 days of bleeding or spotting based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding or spotting, based on imputed electronic diary data during the last 56 days of treatment. Participants needed to have at least 66 days on treatment.
    Time Frame Last 56 days of treatment (after 10 days from first dose date)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with < 66 days of treatment.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 61 57 57 60 75 67 63 66
    Number [percentage of participants]
    1.6
    2.5%
    56.1
    86.3%
    33.3
    52%
    28.3
    43.5%
    1.3
    1.7%
    50.7
    65.8%
    17.5
    23%
    22.7
    29.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    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 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    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: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    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: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    7. Secondary Outcome
    Title Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment
    Description Suppression of bleeding is defined as having 0 days of bleeding based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding (spotting is allowed) based on imputed electronic diary data during the last 56 days of treatment.
    Time Frame Last 56 days of treatment (after 10 days from first dose date)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with < 66 days of treatment.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 61 57 57 60 75 67 63 66
    Number [percentage of participants]
    1.6
    2.5%
    75.4
    116%
    52.6
    82.2%
    43.3
    66.6%
    2.7
    3.5%
    67.2
    87.3%
    31.7
    41.7%
    34.8
    45.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    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 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    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: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    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: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments
    Method Fisher Exact
    Comments
    8. Secondary Outcome
    Title Mean Change in the Number of Bleeding Days From Baseline to Month 6
    Description The number of days with any bleeding including spotting was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.
    Time Frame Baseline, Month 6

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and Month 6.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 37 11 26 30 47 15 26 28
    Least Squares Mean (Standard Error) [days]
    -1.2
    (0.63)
    -4.9
    (1.15)
    -2.7
    (0.75)
    -1.1
    (0.69)
    -1.4
    (0.49)
    -3.3
    (0.87)
    -1.3
    (0.66)
    -1.8
    (0.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -6.28 to -1.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.32
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.132
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -3.44 to 0.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.98
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.876
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -1.71 to 2.00
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.94
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.055
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -3.92 to 0.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.00
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.898
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -1.52 to 1.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.82
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.59
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -2.05 to 1.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.81
    Estimation Comments
    9. Secondary Outcome
    Title Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6
    Description The number of days with heavy bleeding (either heavy or very heavy/gushing bleeding) was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.
    Time Frame Baseline, Month 6

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and Month 6.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 37 11 26 30 47 15 26 28
    Least Squares Mean (Standard Error) [days]
    -1.0
    (0.15)
    -2.0
    (0.27)
    -1.9
    (0.18)
    -1.7
    (0.16)
    -0.7
    (0.14)
    -1.2
    (0.25)
    -1.4
    (0.19)
    -1.8
    (0.18)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -1.00
    Confidence Interval (2-Sided) 95%
    -1.64 to -0.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.31
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -1.00
    Confidence Interval (2-Sided) 95%
    -1.42 to -0.48
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.23
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.12 to -0.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.22
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.118
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -1.04 to 0.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.16 to -0.22
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -1.00
    Confidence Interval (2-Sided) 95%
    -1.51 to -0.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.23
    Estimation Comments
    10. Secondary Outcome
    Title Change in Bleeding Severity Scores From Baseline at the Final Month
    Description The average bleeding score was calculated for each 28-day interval starting on Day 29 using data collected on daily bleeding diary using the Mansfield-Voda-Jorgenson (MVJ) Menstrual Bleeding Scale (1=spotting, 2 = very light bleeding, 3 = light bleeding, 4 = moderate bleeding, 5 = heavy bleeding, 6 = very heavy/gushing bleeding). Baseline is defined as the last 28 days prior to the first day of study drug.
    Time Frame Baseline, Final Month (last 28 days of treatment)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and final month.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 51 19 33 37 61 24 48 42
    Least Squares Mean (Standard Error) [units on a scale]
    -0.3
    (0.08)
    -0.7
    (0.14)
    -0.4
    (0.10)
    -0.1
    (0.10)
    -0.2
    (0.08)
    -0.4
    (0.14)
    -0.3
    (0.10)
    -0.1
    (0.10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -0.79 to -0.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.314
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.13
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.307
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.12 to 0.39
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.106
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.58 to 0.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.424
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.36 to 0.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.528
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS mean change
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.18 to 0.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    11. Secondary Outcome
    Title Mean Change in Hemoglobin Concentration From Baseline to Final Visit
    Description Baseline is defined as the last measurement prior to the first dose of study drug.
    Time Frame Baseline, Final Visit during treatment period (Month 6 or early termination)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and final month.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 64 61 59 61 76 71 72 74
    Least Squares Mean (Standard Error) [g/dL]
    0.6
    (0.17)
    1.9
    (0.17)
    1.9
    (0.17)
    1.4
    (0.17)
    0.3
    (0.15)
    1.4
    (0.16)
    1.1
    (0.16)
    1.2
    (0.16)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    0.80 to 1.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    0.78 to 1.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value 0.8
    Confidence Interval (2-Sided) 95%
    0.33 to 1.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.65 to 1.52
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.22
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    0.29 to 1.16
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.22
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value 0.8
    Confidence Interval (2-Sided) 95%
    0.4 to 1.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.22
    Estimation Comments
    12. Secondary Outcome
    Title Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit
    Description Volume of the total fibroid volume (3 largest fibroids), as measured by transvaginal ultrasound, or transabdominal ultrasound.
    Time Frame Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and final month.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 65 65 64 65 78 77 76 77
    Month 3
    1.7
    (33.61)
    -41.9
    (24.87)
    -24.6
    (27.58)
    -9.8
    (40.31)
    5.4
    (27.18)
    -34.4
    (25.56)
    -17.5
    (27.76)
    -4.6
    (39.97)
    Month 6
    8.3
    (50.97)
    -40.2
    (27.6)
    -23.3
    (30.34)
    -8.8
    (47.81)
    -1.8
    (30.1)
    -34.2
    (31.14)
    -17.8
    (30.49)
    -1.1
    (46.66)
    Final Visit
    4.6
    (48.59)
    -39.6
    (28.66)
    -24.0
    (29.93)
    -12.9
    (46.2)
    0.1
    (28.82)
    -36.4
    (30.07)
    -16.6
    (32.65)
    -1.6
    (42.75)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.021
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.032
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.495
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.329
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    13. Secondary Outcome
    Title Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit
    Description Volume of the largest fibroid (primary fibroid), as measured by transvaginal ultrasound, or transabdominal ultrasound.
    Time Frame Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 65 65 64 65 78 77 76 77
    Month 3
    6.9
    (35.31)
    -35.5
    (26.32)
    -20.3
    (33.54)
    -3.7
    (39.13)
    6.7
    (27.66)
    -33.6
    (23.74)
    -17.2
    (27.39)
    -1.9
    (39.22)
    Month 6
    13.2
    (48.65)
    -36.1
    (30.59)
    -19.6
    (32.1)
    0.0
    (47.07)
    1.4
    (30.03)
    -33.5
    (31.89)
    -12.2
    (40.59)
    -0.7
    (42.98)
    Final Visit
    9.0
    (46.63)
    -35.6
    (30.81)
    20.0
    (31.73)
    -2.7
    (46.63)
    3.0
    (28.7)
    -34.8
    (30.36)
    -12.8
    (39.65)
    0.0
    (40.17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.036
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.040
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.098
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.409
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.094
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.393
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    14. Secondary Outcome
    Title Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit
    Description Uterine volume, as measured by transvaginal ultrasound or transabdominal ultrasound.
    Time Frame Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 65 65 64 65 78 77 76 77
    Month 3
    7.3
    (25.12)
    -30.9
    (28.87)
    -19.4
    (22.48)
    -7.3
    (20.7)
    8.4
    (24.26)
    -24.7
    (21.98)
    -15.7
    (21.84)
    -6.1
    (18.81)
    Month 6
    17.5
    (40.25)
    -35.6
    (25.74)
    -21.9
    (27.64)
    -13.2
    (23.86)
    10.7
    (20.73)
    -26.00
    (29.51)
    -13.5
    (25.09)
    -9.0
    (22.12)
    Final Visit
    15.9
    (38.06)
    -31.5
    (31.44)
    -22.0
    (28.52)
    -11.8
    (22.56)
    11.6
    (25.38)
    -26.6
    (28.26)
    -11.5
    (25.33)
    -6.7
    (21.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from Kruskal-Wallis analysis with treatment as the main effect.
    Method Kruskal-Wallis
    Comments
    15. Secondary Outcome
    Title Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit
    Description Total fibroid volume (3 largest fibroids) was measured by transvaginal ultrasound, or transabdominal ultrasound.
    Time Frame Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 65 65 64 65 78 77 76 77
    Month 3
    13.2
    20.3%
    79.6
    122.5%
    50.0
    78.1%
    31.9
    49.1%
    9.4
    12.1%
    66.7
    86.6%
    34.0
    44.7%
    22.4
    29.1%
    Month 6
    24.4
    37.5%
    75.0
    115.4%
    54.2
    84.7%
    40.5
    62.3%
    18.2
    23.3%
    62.0
    80.5%
    40.9
    53.8%
    34.8
    45.2%
    Final Visit
    24.5
    37.7%
    73.6
    113.2%
    57.4
    89.7%
    41.2
    63.4%
    16.7
    21.4%
    64.4
    83.6%
    40.0
    52.6%
    30.0
    39%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.061
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.085
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.049
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.056
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.088
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    16. Secondary Outcome
    Title Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit
    Description Volume of the largest fibroid (primary fibroid) was measured by transvaginal ultrasound or transabdominal ultrasound.
    Time Frame Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 65 65 64 65 78 77 76 77
    Month 3
    13.2
    20.3%
    67.3
    103.5%
    46.2
    72.2%
    23.4
    36%
    10.9
    14%
    63.2
    82.1%
    37.7
    49.6%
    22.4
    29.1%
    Month 6
    24.4
    37.5%
    70.5
    108.5%
    47.9
    74.8%
    26.2
    40.3%
    14.5
    18.6%
    64.0
    83.1%
    38.6
    50.8%
    34.8
    45.2%
    Final Visit
    24.5
    37.7%
    69.8
    107.4%
    50.0
    78.1%
    27.5
    42.3%
    13.6
    17.4%
    66.1
    85.8%
    40.0
    52.6%
    30.0
    39%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.188
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.104
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.021
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.859
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.722
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.032
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    17. Secondary Outcome
    Title Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit
    Description Uterine volume was measured by transvaginal ultrasound or transabdominal ultrasound.
    Time Frame Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 65 65 64 65 78 77 76 77
    Month 3
    5.2
    8%
    73.1
    112.5%
    42.9
    67%
    18.5
    28.5%
    1.4
    1.8%
    57.1
    74.2%
    36.8
    48.4%
    17.5
    22.7%
    Month 6
    2.0
    3.1%
    78.7
    121.1%
    58.0
    90.6%
    31.9
    49.1%
    1.6
    2.1%
    62.5
    81.2%
    32.7
    43%
    26.0
    33.8%
    Final Visit
    3.4
    5.2%
    73.2
    112.6%
    58.9
    92%
    26.8
    41.2%
    1.4
    1.8%
    63.1
    81.9%
    29.3
    38.6%
    23.4
    30.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.041
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 3
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Final Visit
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.
    Method Regression, Logistic
    Comments
    18. Secondary Outcome
    Title Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire
    Description The NBUFSQ (8 items) is a brief patient-reported daily diary that assesses non-bleeding symptoms experienced by women with uterine fibroids. It includes 6 items, asking women to rate their symptoms (abdominal/pelvic pain, pressure, and cramping, back pain, bloating, and urinary problems) in the past 24 hours using an 11-point numeric response scale that ranges from 0 (i.e., no symptom) to 10 (i.e., worst possible symptom) and 2 items to address urinary frequency during the daytime and at night. Data presented in the sum of scores to the 6 symptom questions, ranging from 0 (no symptoms) to 60 (worst possible symptoms). Baseline is defined as the last 28 days prior to the first day of study drug. Final Month is defined as the last 28 days prior to and including the last dose date of study drug.
    Time Frame Baseline, Days 1-28, Days 29-56, Days 57-84, Days 85-112, Days 113-140, Days 141-168, Final Month of treatment, Post-treatment (PT) Days 1-28, PT Days 29-56, PT Days 57-84, PT Days 85-112, PT Days 113-140, PT Days 141-168

    Outcome Measure Data

    Analysis Population Description
    Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 65 65 64 65 78 77 76 77
    Days 1-28
    -3.3
    (10.11)
    -3.4
    (8.21)
    -3.1
    (7.88)
    -1.4
    (6.42)
    0.4
    (4.71)
    -2.7
    (7.27)
    -2.1
    (4.44)
    0.0
    (6.26)
    Days 29-56
    -4.5
    (13.12)
    -5.8
    (8.78)
    -4.4
    (6.59)
    -2.9
    (9.44)
    -0.3
    (7.13)
    -4.2
    (7.72)
    -2.2
    (5.54)
    -2.3
    (9.31)
    Days 57-84
    -5.6
    (10.94)
    -7.2
    (11.04)
    -4.1
    (8.4)
    -3.2
    (11.26)
    0.1
    (7.34)
    -4.5
    (8.55)
    -2.2
    (6.22)
    -3.8
    (8.92)
    Days 85-112
    -7.0
    (10.74)
    -7.8
    (11.75)
    -5.2
    (9.05)
    -3.7
    (10.76)
    -0.2
    (7.47)
    -5.1
    (9.40)
    -3.6
    (7.35)
    -4.1
    (8.96)
    Days 113-140
    -4.1
    (13.16)
    -7.6
    (12.03)
    -5.3
    (9.43)
    -3.4
    (12.1)
    0.1
    (11.92)
    -5.5
    (8.44)
    -4.0
    (8.13)
    -5.3
    (8.99)
    Days 141-168
    -6.8
    (14.28)
    -8.0
    (12.65)
    -5.1
    (9.94)
    -3.3
    (13.01)
    -0.4
    (10.46)
    -5.9
    (9.45)
    -4.4
    (8.21)
    -4.8
    (9.3)
    Final Month
    -5.3
    (13.19)
    -6.7
    (11.94)
    -4.1
    (10.15)
    -3.5
    (12.59)
    -0.8
    (11.34)
    -4.0
    (9.40)
    -3.3
    (8.09)
    -2.3
    (10.56)
    PT Days 1-28
    -5.6
    (13.39)
    -5.2
    (12.13)
    -3.8
    (10.37)
    -3.0
    (10.69)
    -0.8
    (12.46)
    -3.8
    (10.53)
    -2.0
    (8.23)
    -2.3
    (7.82)
    PT Days 29-56
    -5.7
    (15.83)
    -4.1
    (13.1)
    -1.0
    (11.57)
    0.0
    (9.89)
    -0.2
    (12.49)
    -2.8
    (11.85)
    -2.7
    (7.58)
    -2.5
    (8.54)
    PT Days 57-84
    -5.4
    (17.08)
    -4.0
    (14.11)
    -2.1
    (10.91)
    -1.1
    (10.50)
    -0.5
    (13.08)
    -2.0
    (9.79)
    -1.6
    (8.35)
    -3.9
    (6.87)
    PT Days 85-112
    -4.4
    (17.82)
    -6.4
    (12.99)
    -4.8
    (10.33)
    0.7
    (6.59)
    -2.7
    (7.15)
    -2.4
    (14.37)
    -3.0
    (7.48)
    -5.0
    (5.12)
    PT Days 113-140
    3.4
    (27.8)
    -3.1
    (2.15)
    1.3
    (NA)
    1.4
    (1.75)
    -6.2
    (1.51)
    -17.3
    (26.2)
    -5.6
    (6.45)
    -7.0
    (7.12)
    PT Days 141-168
    7.5
    (27.75)
    -8.0
    (1.42)
    4.1
    (NA)
    -3.3
    (NA)
    -10.5
    (NA)
    -3.1
    (NA)
    -3.3
    (6.42)
    -6.4
    (5.94)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID
    Comments Final Month
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.556
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from ANCOVA model with treatment as the main effect and baseline as covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -6.65 to 3.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.58
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD
    Comments Final Month
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.672
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from ANCOVA model with treatment as the main effect and baseline as covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -6.33 to 4.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.63
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo, Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD
    Comments Final Month
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.274
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from ANCOVA model with treatment as the main effect and baseline as covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value 3.0
    Confidence Interval (2-Sided) 95%
    -2.39 to 8.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.71
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD
    Comments Final Month
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.223
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from ANCOVA model with treatment as the main effect and baseline as covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -5.26 to 1.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.65
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD
    Comments Final Month
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.215
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from ANCOVA model with treatment as the main effect and baseline as covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -5.38 to 1.22
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.68
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Cohort 2: Placebo, Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Comments Final Month
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.392
    Comments P value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from ANCOVA model with treatment as the main effect and baseline as covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter difference in LS means
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -4.75 to 1.87
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.68
    Estimation Comments
    19. Secondary Outcome
    Title Percentage of Participants Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids
    Description The percentage of participants who successfully avoided surgical or invasive procedures for Uterine Fibroids was assessed.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    This endpoint was not completed due to lack of data collection.
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    Measure Participants 0 0 0 0 0 0 0 0

    Adverse Events

    Time Frame From the time of study drug administration through Final Visit (Month 6 or early termination) plus 30 days
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    Arm/Group Description Placebo for elagolix BID and placebo for E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD Placebo for elagolix QD and placebo for E2/NETA QD Elagolix 600 mg QD and placebo for E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD
    All Cause Mortality
    Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    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 0/65 (0%) 0/65 (0%) 0/64 (0%) 0/65 (0%) 0/78 (0%) 0/77 (0%) 0/76 (0%) 0/77 (0%)
    Serious Adverse Events
    Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    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 6/65 (9.2%) 3/65 (4.6%) 3/64 (4.7%) 1/65 (1.5%) 1/78 (1.3%) 5/77 (6.5%) 3/76 (3.9%) 4/77 (5.2%)
    Blood and lymphatic system disorders
    ANAEMIA 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 1/65 (1.5%) 1 1/78 (1.3%) 1 1/77 (1.3%) 1 0/76 (0%) 0 1/77 (1.3%) 1
    IRON DEFICIENCY ANAEMIA 1/65 (1.5%) 1 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    Cardiac disorders
    CORONARY ARTERY DISEASE 0/65 (0%) 0 0/65 (0%) 0 1/64 (1.6%) 1 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    Gastrointestinal disorders
    DIVERTICULAR PERFORATION 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1 0/76 (0%) 0 0/77 (0%) 0
    Infections and infestations
    APPENDICITIS 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 1/76 (1.3%) 1 0/77 (0%) 0
    PNEUMONIA 1/65 (1.5%) 1 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1 0/76 (0%) 0 0/77 (0%) 0
    VARICELLA 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1 0/76 (0%) 0 0/77 (0%) 0
    Injury, poisoning and procedural complications
    CONCUSSION 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 1/76 (1.3%) 1 0/77 (0%) 0
    CONTUSION 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 1/77 (1.3%) 1
    MENISCUS INJURY 1/65 (1.5%) 1 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    ROAD TRAFFIC ACCIDENT 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 1/76 (1.3%) 1 0/77 (0%) 0
    Musculoskeletal and connective tissue disorders
    NECK PAIN 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 1/77 (1.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BREAST CANCER 1/65 (1.5%) 1 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    ENDOMETRIAL ADENOCARCINOMA 0/65 (0%) 0 1/65 (1.5%) 1 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    GASTRINOMA MALIGNANT 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1 0/76 (0%) 0 0/77 (0%) 0
    UTERINE LEIOMYOMA 0/65 (0%) 0 0/65 (0%) 0 1/64 (1.6%) 1 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 1/76 (1.3%) 1 0/77 (0%) 0
    Nervous system disorders
    SYNCOPE 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 1/77 (1.3%) 1
    Reproductive system and breast disorders
    CYSTOCELE 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1 0/76 (0%) 0 0/77 (0%) 0
    DYSMENORRHOEA 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 1/76 (1.3%) 1 0/77 (0%) 0
    MENORRHAGIA 1/65 (1.5%) 1 1/65 (1.5%) 1 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 1/76 (1.3%) 1 0/77 (0%) 0
    PELVIC PAIN 1/65 (1.5%) 1 1/65 (1.5%) 1 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    UTERINE HAEMORRHAGE 1/65 (1.5%) 1 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    ASTHMA 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 1/77 (1.3%) 1
    PULMONARY EMBOLISM 0/65 (0%) 0 1/65 (1.5%) 1 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    Vascular disorders
    DEEP VEIN THROMBOSIS 0/65 (0%) 0 1/65 (1.5%) 1 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    HAEMATOMA 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 1/77 (1.3%) 1
    HYPERTENSION 0/65 (0%) 0 0/65 (0%) 0 1/64 (1.6%) 1 0/65 (0%) 0 0/78 (0%) 0 0/77 (0%) 0 0/76 (0%) 0 0/77 (0%) 0
    Other (Not Including Serious) Adverse Events
    Cohort 1: Placebo Cohort 1: Elagolix 300 mg BID Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Cohort 2: Placebo Cohort 2: Elagolix 600 mg QD Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD
    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 33/65 (50.8%) 45/65 (69.2%) 37/64 (57.8%) 44/65 (67.7%) 42/78 (53.8%) 59/77 (76.6%) 43/76 (56.6%) 51/77 (66.2%)
    Blood and lymphatic system disorders
    ANAEMIA 6/65 (9.2%) 6 1/65 (1.5%) 1 2/64 (3.1%) 2 2/65 (3.1%) 2 6/78 (7.7%) 6 3/77 (3.9%) 3 6/76 (7.9%) 6 4/77 (5.2%) 4
    Gastrointestinal disorders
    ABDOMINAL DISTENSION 1/65 (1.5%) 1 1/65 (1.5%) 1 0/64 (0%) 0 1/65 (1.5%) 1 3/78 (3.8%) 3 6/77 (7.8%) 6 1/76 (1.3%) 1 3/77 (3.9%) 3
    ABDOMINAL PAIN 2/65 (3.1%) 2 1/65 (1.5%) 1 2/64 (3.1%) 2 2/65 (3.1%) 2 2/78 (2.6%) 3 3/77 (3.9%) 3 3/76 (3.9%) 3 4/77 (5.2%) 4
    ABDOMINAL PAIN LOWER 0/65 (0%) 0 4/65 (6.2%) 4 0/64 (0%) 0 0/65 (0%) 0 2/78 (2.6%) 2 1/77 (1.3%) 1 0/76 (0%) 0 4/77 (5.2%) 5
    ABDOMINAL PAIN UPPER 0/65 (0%) 0 0/65 (0%) 0 1/64 (1.6%) 4 0/65 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1 0/76 (0%) 0 4/77 (5.2%) 5
    DIARRHOEA 3/65 (4.6%) 3 1/65 (1.5%) 1 2/64 (3.1%) 2 5/65 (7.7%) 6 4/78 (5.1%) 4 5/77 (6.5%) 5 3/76 (3.9%) 3 4/77 (5.2%) 5
    NAUSEA 6/65 (9.2%) 6 4/65 (6.2%) 4 4/64 (6.3%) 4 12/65 (18.5%) 13 3/78 (3.8%) 4 10/77 (13%) 11 12/76 (15.8%) 12 20/77 (26%) 23
    VOMITING 1/65 (1.5%) 2 1/65 (1.5%) 1 0/64 (0%) 0 3/65 (4.6%) 3 4/78 (5.1%) 5 4/77 (5.2%) 6 3/76 (3.9%) 3 5/77 (6.5%) 7
    General disorders
    FATIGUE 2/65 (3.1%) 2 3/65 (4.6%) 3 4/64 (6.3%) 4 3/65 (4.6%) 3 3/78 (3.8%) 3 0/77 (0%) 0 1/76 (1.3%) 1 5/77 (6.5%) 5
    Infections and infestations
    BACTERIAL VAGINOSIS 4/65 (6.2%) 4 4/65 (6.2%) 6 4/64 (6.3%) 5 1/65 (1.5%) 1 2/78 (2.6%) 2 2/77 (2.6%) 2 1/76 (1.3%) 1 0/77 (0%) 0
    NASOPHARYNGITIS 4/65 (6.2%) 4 3/65 (4.6%) 3 4/64 (6.3%) 4 0/65 (0%) 0 1/78 (1.3%) 1 2/77 (2.6%) 2 3/76 (3.9%) 3 4/77 (5.2%) 5
    SINUSITIS 0/65 (0%) 0 2/65 (3.1%) 2 2/64 (3.1%) 2 2/65 (3.1%) 2 5/78 (6.4%) 5 2/77 (2.6%) 2 2/76 (2.6%) 2 1/77 (1.3%) 1
    UPPER RESPIRATORY TRACT INFECTION 1/65 (1.5%) 2 3/65 (4.6%) 3 1/64 (1.6%) 1 1/65 (1.5%) 2 0/78 (0%) 0 4/77 (5.2%) 6 2/76 (2.6%) 2 2/77 (2.6%) 2
    URINARY TRACT INFECTION 2/65 (3.1%) 2 2/65 (3.1%) 3 5/64 (7.8%) 7 4/65 (6.2%) 4 5/78 (6.4%) 5 1/77 (1.3%) 1 2/76 (2.6%) 2 2/77 (2.6%) 2
    VULVOVAGINAL MYCOTIC INFECTION 1/65 (1.5%) 1 0/65 (0%) 0 2/64 (3.1%) 3 4/65 (6.2%) 4 2/78 (2.6%) 2 1/77 (1.3%) 1 0/76 (0%) 0 2/77 (2.6%) 2
    Investigations
    BLOOD CHOLESTEROL INCREASED 1/65 (1.5%) 1 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 4/77 (5.2%) 4 4/76 (5.3%) 5 2/77 (2.6%) 2
    BONE DENSITY DECREASED 1/65 (1.5%) 1 5/65 (7.7%) 5 2/64 (3.1%) 2 1/65 (1.5%) 1 2/78 (2.6%) 2 1/77 (1.3%) 1 1/76 (1.3%) 1 0/77 (0%) 0
    LIPIDS INCREASED 0/65 (0%) 0 0/65 (0%) 0 0/64 (0%) 0 0/65 (0%) 0 0/78 (0%) 0 4/77 (5.2%) 4 0/76 (0%) 0 0/77 (0%) 0
    WEIGHT INCREASED 0/65 (0%) 0 1/65 (1.5%) 1 1/64 (1.6%) 1 0/65 (0%) 0 0/78 (0%) 0 6/77 (7.8%) 6 1/76 (1.3%) 1 1/77 (1.3%) 1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 3/65 (4.6%) 3 3/65 (4.6%) 6 3/64 (4.7%) 3 0/65 (0%) 0 3/78 (3.8%) 3 5/77 (6.5%) 5 4/76 (5.3%) 4 1/77 (1.3%) 1
    BACK PAIN 6/65 (9.2%) 6 5/65 (7.7%) 5 2/64 (3.1%) 2 3/65 (4.6%) 3 2/78 (2.6%) 2 6/77 (7.8%) 7 6/76 (7.9%) 7 7/77 (9.1%) 7
    MUSCLE SPASMS 2/65 (3.1%) 2 0/65 (0%) 0 1/64 (1.6%) 1 2/65 (3.1%) 2 2/78 (2.6%) 4 5/77 (6.5%) 5 1/76 (1.3%) 1 3/77 (3.9%) 3
    MUSCULOSKELETAL PAIN 1/65 (1.5%) 1 4/65 (6.2%) 4 1/64 (1.6%) 1 0/65 (0%) 0 0/78 (0%) 0 3/77 (3.9%) 3 0/76 (0%) 0 0/77 (0%) 0
    PAIN IN EXTREMITY 2/65 (3.1%) 2 4/65 (6.2%) 4 2/64 (3.1%) 2 4/65 (6.2%) 4 0/78 (0%) 0 2/77 (2.6%) 2 1/76 (1.3%) 1 2/77 (2.6%) 2
    Nervous system disorders
    DIZZINESS 3/65 (4.6%) 3 3/65 (4.6%) 3 1/64 (1.6%) 1 3/65 (4.6%) 3 3/78 (3.8%) 4 3/77 (3.9%) 3 4/76 (5.3%) 5 5/77 (6.5%) 5
    HEADACHE 6/65 (9.2%) 7 8/65 (12.3%) 8 9/64 (14.1%) 9 13/65 (20%) 14 8/78 (10.3%) 9 13/77 (16.9%) 15 11/76 (14.5%) 11 14/77 (18.2%) 14
    Psychiatric disorders
    INSOMNIA 1/65 (1.5%) 1 7/65 (10.8%) 7 5/64 (7.8%) 5 0/65 (0%) 0 2/78 (2.6%) 2 4/77 (5.2%) 4 2/76 (2.6%) 2 5/77 (6.5%) 5
    Reproductive system and breast disorders
    DYSMENORRHOEA 2/65 (3.1%) 2 2/65 (3.1%) 2 1/64 (1.6%) 1 3/65 (4.6%) 3 2/78 (2.6%) 2 2/77 (2.6%) 2 5/76 (6.6%) 6 3/77 (3.9%) 4
    MENORRHAGIA 1/65 (1.5%) 1 2/65 (3.1%) 2 3/64 (4.7%) 3 4/65 (6.2%) 6 2/78 (2.6%) 2 1/77 (1.3%) 1 2/76 (2.6%) 2 7/77 (9.1%) 8
    PELVIC PAIN 0/65 (0%) 0 2/65 (3.1%) 2 1/64 (1.6%) 1 3/65 (4.6%) 3 1/78 (1.3%) 1 0/77 (0%) 0 1/76 (1.3%) 1 5/77 (6.5%) 5
    Vascular disorders
    HOT FLUSH 2/65 (3.1%) 2 29/65 (44.6%) 32 16/64 (25%) 16 7/65 (10.8%) 7 4/78 (5.1%) 4 38/77 (49.4%) 39 14/76 (18.4%) 14 11/77 (14.3%) 11
    HYPERTENSION 3/65 (4.6%) 3 1/65 (1.5%) 1 1/64 (1.6%) 1 5/65 (7.7%) 5 0/78 (0%) 0 5/77 (6.5%) 6 2/76 (2.6%) 2 1/77 (1.3%) 1

    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
    Phone 800-633-9110
    Email abbvieclinicaltrials@abbvie.com
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT01817530
    Other Study ID Numbers:
    • M12-813
    • 2013-000082-37