Efficacy and Safety of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (Replicate Study)

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT02691494
Collaborator
(none)
378
105
3
35.6
3.6
0.1

Study Details

Study Description

Brief Summary

This study seeks to evaluate the efficacy, safety and tolerability of elagolix alone and in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Condition or Disease Intervention/Treatment Phase
  • Drug: Elagolix
  • Drug: Placebo for Estradiol/Norethindrone Acetate
  • Drug: Estradiol/Norethindrone Acetate
  • Drug: Placebo for Elagolix
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
378 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Study to Evaluate the Efficacy and Safety of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women
Actual Study Start Date :
Feb 3, 2016
Actual Primary Completion Date :
Feb 14, 2018
Actual Study Completion Date :
Jan 23, 2019

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Placebo for both elagolix twice daily (BID) and norethindrone acetate (E2/ NETA) once daily (QD)

Drug: Placebo for Estradiol/Norethindrone Acetate
Placebo capsules

Drug: Placebo for Elagolix
Film-coated placebo tablets

Experimental: Elagolix

Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD

Drug: Elagolix
Film-coated tablets
Other Names:
  • ABT-620
  • elagolix sodium
  • Drug: Placebo for Estradiol/Norethindrone Acetate
    Placebo capsules

    Experimental: Elagolix + E2/NETA

    Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD

    Drug: Elagolix
    Film-coated tablets
    Other Names:
  • ABT-620
  • elagolix sodium
  • Drug: Estradiol/Norethindrone Acetate
    Commercially-available E2/NETA tablets were over-encapsulated to maintain study blinding.
    Other Names:
  • E2/NETA
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Meeting the Criteria for Responder [Final Month (the last 28 days prior to and including the Reference Day), up to Month 6]

      Percentage of responders, defined as participants who met the following conditions: Menstrual blood loss (MBL) volume < 80 mL during the Final Month (the last 28 days prior to and including the Reference Day, which is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date), and ≥ 50% reduction in MBL volume from Baseline to the Final Month. Participants who prematurely discontinued study drug due to "lack of efficacy," "requires surgery or invasive intervention for treatment of uterine fibroids," or "adverse events" were considered non-responders regardless of whether she meets the two aforementioned responder criteria or not.

    Secondary Outcome Measures

    1. Change From Baseline in MBL Volume to the Final Month [Baseline and Final Month (the last 28 days prior to and including the Reference Day), up to Month 6]

      Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.

    2. Percentage of Participants With Suppression of Bleeding at the Final Month [Final Month (the last 28 days prior to and including the Reference Day), up to Month 6]

      Suppression of bleeding is defined as having 0 days of bleeding (spotting is allowed) during the Final Month with the interval starting from Study Day 11. The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.

    3. Change From Baseline in MBL Volume to Month 6 [Month 0 (Baseline), Month 6]

      Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

    4. Change From Baseline in MBL Volume to Month 3 [Month 0 (Baseline), Month 3]

      Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

    5. Percentage of Participants With Baseline Hemoglobin <= 10.5 g/dL Who Have an Increase in Hemoglobin > 2 g/dL at Month 6 [Month 0 (Baseline), Month 6]

    6. Change From Baseline in MBL Volume to Month 1 [Month 0 (Baseline), Month 1]

      Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

    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 a premenopausal female at the time of Screening.

    • Subject has a diagnosis of uterine fibroids documented by a pelvic ultrasound (transabdominal ultrasound/transvaginal ultrasound).

    • Subject has heavy menstrual bleeding associated with uterine fibroids as evidenced by menstrual blood loss > 80 mL during each of two screening menses as measured by the alkaline hematin method.

    • Subject has negative urine and/or serum pregnancy test in Screening and just prior to first dose.

    • Subject has an adequate endometrial biopsy performed during Screening, the results of which show no clinically significant endometrial pathology.

    Exclusion Criteria:
    • Subject has screening pelvic ultrasound or saline infusion sonohysterography results that show a clinically significant gynecological disorder.

    • Subject has history of osteoporosis or other metabolic bone disease.

    • Subject has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.

    • Subject has a history of major depression or post-traumatic stress disorder (PTSD) within 2 years of screening, OR a history of other major psychiatric disorder at any time (e.g., schizophrenia, bipolar disorder).

    • Subject is using any systemic corticosteroids for over 14 days within 3 months prior to Screening or is likely to require treatment with systemic corticosteroids during the course of the study. Over the counter and prescription topical, inhaled, intranasal or injectable (for occasional use) corticosteroids are allowed.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alabama Clinical Therapeutics, LLC /ID# 152258 Birmingham Alabama United States 35235-3430
    2 Choice Research, LLC /ID# 150988 Dothan Alabama United States 36303
    3 Brown, Pearson, Guepet Gynecology /ID# 151020 Fairhope Alabama United States 36532
    4 Mobile, Ob-Gyn, P.C. /ID# 144294 Mobile Alabama United States 36608
    5 Mesa Obstetricians and Gynecol /ID# 149139 Mesa Arizona United States 85209
    6 Visions Clinical Research-Tucs /ID# 151017 Tucson Arizona United States 85712
    7 Core Healthcare Group /ID# 151016 Cerritos California United States 90703
    8 Diagnamics Inc. /ID# 152469 Encinitas California United States 92024
    9 HCP Clinical Research LLC /ID# 154434 Huntington Beach California United States 92646
    10 Alliance Research Centers /ID# 149752 Laguna Hills California United States 92653-3621
    11 University of California, Los Angeles /ID# 149760 Los Angeles California United States 90095
    12 Futura Research, Inc. /ID# 149759 Norwalk California United States 90650
    13 Farid Yasharpour MD Medical Co /ID# 149770 San Fernando California United States 91340
    14 Clinical Trial Investigators /ID# 152470 Tustin California United States 92780
    15 Bayview Research Group LLC /ID# 153799 Valley Village California United States 91607
    16 Emerson Clinical Research Inst /ID# 152348 Washington District of Columbia United States 20011
    17 Ideal Clinical Research Inc. /ID# 149757 Aventura Florida United States 33180
    18 Seffner Premier Health Care, P /ID# 167480 Brandon Florida United States 33510
    19 Olympian Clinical Research /ID# 149756 Clearwater Florida United States 33756
    20 KO Clinical Research, LLC /ID# 144299 Fort Lauderdale Florida United States 33316
    21 University of Florida /ID# 149751 Gainesville Florida United States 32610
    22 Solutions Through Adv Rch /ID# 151021 Jacksonville Florida United States 32256
    23 Meridien Research /ID# 167100 Kenneth City Florida United States 33709-3113
    24 Precision Research Org, LLC /ID# 144335 Miami Lakes Florida United States 33016-1501
    25 Invictus Clinical Research Group,LLC /ID# 141859 Miami Florida United States 33144
    26 Suncoast Clinical Research /ID# 149765 New Port Richey Florida United States 34652
    27 All Wmns HC of West Broward /ID# 144298 Plantation Florida United States 33324
    28 Oncova Clinical Research, Inc. /ID# 149764 Saint Cloud Florida United States 34769
    29 Physician Care Clin. Res., LLC /ID# 149766 Sarasota Florida United States 34239
    30 Qps-Mra, Llc /Id# 144325 South Miami Florida United States 33143
    31 Martin Health System Center /ID# 152263 Stuart Florida United States 34994
    32 University of South Florida /ID# 149754 Tampa Florida United States 33612
    33 Axcess Medical Research /ID# 149769 Wellington Florida United States 33414
    34 Virtus Research Consultant,LLC /ID# 144296 Wellington Florida United States 33414
    35 Paramount Research Solutions /ID# 149291 Alpharetta Georgia United States 30005
    36 Agile Clinical Research Trials /ID# 167074 Atlanta Georgia United States 30328
    37 Mount Vernon Clinical Res, LLC /ID# 144297 Atlanta Georgia United States 30328
    38 Atlanta Women's Research Inst /ID# 144303 Atlanta Georgia United States 30342
    39 Masters of Clinical Research, Inc. /ID# 167400 Augusta Georgia United States 30909
    40 Georgia Regents University /ID# 144295 Augusta Georgia United States 30912
    41 Meridian Clinical Research, LLC /ID# 149144 Savannah Georgia United States 31406-2675
    42 Gyn-Care, Inc. /ID# 149341 Smyrna Georgia United States 30080
    43 Atlanta Gynecology Research Institute /ID# 151014 Suwanee Georgia United States 30024-7159
    44 Womens Healthcare Assoc, DBA /ID# 149762 Idaho Falls Idaho United States 83404
    45 Advanced Clinical Research /ID# 149767 Meridian Idaho United States 83642
    46 University of Chicago /ID# 152257 Chicago Illinois United States 60637-1443
    47 Affinity Clinical Research /ID# 167119 Oak Brook Illinois United States 60523
    48 Center for Women's Research, Inc /ID# 144300 Palos Heights Illinois United States 60463-1440
    49 Women's Health Advantage /ID# 144301 Fort Wayne Indiana United States 46825
    50 The Iowa Clinic /ID# 150105 West Des Moines Iowa United States 50266
    51 PRN Professional Research Network of Kansas, LLC /ID# 152265 Wichita Kansas United States 67205
    52 Bluegrass Clinical Research /ID# 150103 Louisville Kentucky United States 40291
    53 Clinical Trials Management, LLC - Covington /ID# 144314 Covington Louisiana United States 70433
    54 Women Under Study, LLC /ID# 144312 New Orleans Louisiana United States 70125-1923
    55 Baltimore Suburban Health /ID# 154638 Baltimore Maryland United States 21208
    56 Womens Health Center /ID# 154209 Glen Burnie Maryland United States 21063
    57 Maryland Ctr for Sexual Health /ID# 149778 Lutherville Maryland United States 21093
    58 NECCR Fall River LLC /ID# 149584 Fall River Massachusetts United States 02720-2972
    59 Saginaw Valley Med Res Group /ID# 149768 Saginaw Michigan United States 48604
    60 Accent Clinical Trials /ID# 149753 Las Vegas Nevada United States 89106-4017
    61 Jersey Shore University Medical Center /ID# 149779 Neptune New Jersey United States 07753-4859
    62 Rowan University SOM /ID# 152697 Stratford New Jersey United States 08084
    63 Montefiore Medical Center /ID# 149582 Bronx New York United States 10461
    64 SUNY Downstate Medical Center /ID# 144311 Brooklyn New York United States 11203
    65 Manhattan Medical Research /ID# 167077 New York New York United States 10016-6023
    66 Weill Cornell Medicine /ID# 149585 New York New York United States 10032-3725
    67 Duplicate_Unified Women's Clinical Research-Fayetteville /ID# 149587 Fayetteville North Carolina United States 28304
    68 Unified Women's Clinical Research-Greensboro /ID# 149588 Greensboro North Carolina United States 27408
    69 Pinewest Ob-Gyn, Inc. /ID# 145671 High Point North Carolina United States 27262
    70 Eastern Carolina Women's Centr /ID# 144309 New Bern North Carolina United States 28562
    71 Wake Research Associates, LLC /ID# 144307 Raleigh North Carolina United States 27612
    72 Clinical Inquest Center Ltd /ID# 148728 Beavercreek Ohio United States 45432
    73 CTI Clinical Research Center /ID# 149761 Cincinnati Ohio United States 45212
    74 The Christ Hospital /ID# 150104 Cincinnati Ohio United States 45219
    75 Alpha Research Associates LLC /ID# 152471 Dayton Ohio United States 45417
    76 Comprehensive Womens Care /ID# 144306 Westerville Ohio United States 43081
    77 Family Medical Associates /ID# 145668 Levittown Pennsylvania United States 19056
    78 University of Pennsylvania /ID# 149586 Philadelphia Pennsylvania United States 19104-5502
    79 Clinical Research of Philadelphia, LLC /ID# 151015 Philadelphia Pennsylvania United States 19114
    80 Reading Hosp Clncl Trials Ofc /ID# 149583 West Reading Pennsylvania United States 19611
    81 Holston Medical Group /ID# 149763 Bristol Tennessee United States 37620-7346
    82 Chattanooga Medical Research /ID# 145667 Chattanooga Tennessee United States 37404
    83 Chattanooga Women for Women /ID# 167051 Hixson Tennessee United States 37343-3992
    84 The Jackson Clinic, PA /ID# 145670 Jackson Tennessee United States 38305
    85 The Womens Physician Group /ID# 144317 Memphis Tennessee United States 38104
    86 Access Clinical Trials, Inc. /ID# 167333 Nashville Tennessee United States 37203
    87 Lotus Gynecology /ID# 149140 Austin Texas United States 78703-1448
    88 Inquest Clinical Research /ID# 149755 Baytown Texas United States 77521-2415
    89 Texas Health Presbyterian Hosp /ID# 149142 Dallas Texas United States 75231
    90 Baylor College of Medicine /ID# 149141 Houston Texas United States 77030-3411
    91 The Woman's Hospital of Texas /ID# 144319 Houston Texas United States 77054
    92 Centex Studies, Inc. - Houston /ID# 150106 Houston Texas United States 77058
    93 BI Research Center /ID# 149143 Houston Texas United States 77084
    94 FMC Science /ID# 151802 Lampasas Texas United States 76550
    95 Willowbend Health and Wellness /ID# 144318 Plano Texas United States 75035
    96 Clinical Trials of Texas,Inc. /ID# 144322 San Antonio Texas United States 78229
    97 Center of Reproductive Medicin /ID# 167235 Webster Texas United States 77598
    98 Southampton Women's Health /ID# 152325 Franklin Virginia United States 23851
    99 Tidewater Physicians for Women /ID# 144321 Norfolk Virginia United States 23502
    100 Clinical Research Partners, LLC /ID# 144310 Richmond Virginia United States 23220-4459
    101 Alliance Womens Health /ID# 152468 Richmond Virginia United States 23226-1930
    102 Zain Research /ID# 151018 Richland Washington United States 99352
    103 Virginia Mason Medical Center /ID# 149758 Seattle Washington United States 98101
    104 Medicor Research Inc. /ID# 153406 Sudbury Ontario Canada P3A 1W8
    105 Victory Reproductive Care /ID# 150247 Windsor Ontario Canada N8W 5R7

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: AbbVie Inc., AbbVie

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02691494
    Other Study ID Numbers:
    • M12-817
    First Posted:
    Feb 25, 2016
    Last Update Posted:
    Jul 13, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by AbbVie
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Eligible participants were randomized in a 1:1:2 ratio to 1 of 3 treatment groups: placebo, elagolix 300 mg BID, or elagolix 300 mg twice daily (BID) plus estradiol/norethindrone acetate (E2/NETA) once daily (QD).
    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    Period Title: Treatment Period
    STARTED 94 95 189
    COMPLETED 72 69 148
    NOT COMPLETED 22 26 41
    Period Title: Treatment Period
    STARTED 14 25 59
    COMPLETED 9 18 42
    NOT COMPLETED 5 7 17

    Baseline Characteristics

    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA Total
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Total of all reporting groups
    Overall Participants 94 95 189 378
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    42.5
    (5.43)
    42.2
    (5.41)
    42.5
    (5.33)
    42.4
    (5.36)
    Sex: Female, Male (Count of Participants)
    Female
    94
    100%
    95
    100%
    189
    100%
    378
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    11
    11.7%
    17
    17.9%
    31
    16.4%
    59
    15.6%
    Not Hispanic or Latino
    83
    88.3%
    78
    82.1%
    158
    83.6%
    319
    84.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    1.1%
    2
    2.1%
    0
    0%
    3
    0.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    2
    1.1%
    2
    0.5%
    Black or African American
    63
    67%
    66
    69.5%
    124
    65.6%
    253
    66.9%
    White
    30
    31.9%
    27
    28.4%
    59
    31.2%
    116
    30.7%
    More than one race
    0
    0%
    0
    0%
    3
    1.6%
    3
    0.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    0.5%
    1
    0.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Meeting the Criteria for Responder
    Description Percentage of responders, defined as participants who met the following conditions: Menstrual blood loss (MBL) volume < 80 mL during the Final Month (the last 28 days prior to and including the Reference Day, which is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date), and ≥ 50% reduction in MBL volume from Baseline to the Final Month. Participants who prematurely discontinued study drug due to "lack of efficacy," "requires surgery or invasive intervention for treatment of uterine fibroids," or "adverse events" were considered non-responders regardless of whether she meets the two aforementioned responder criteria or not.
    Time Frame Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants.
    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    Measure Participants 94 95 189
    Number [percentage of participants]
    10.5
    11.2%
    76.9
    80.9%
    76.5
    40.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value for test of difference is by pooling the results from a logistic regression model including treatment as the main effect and baseline MBL volume as a covariate in each data set from multiple imputation.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 28.73
    Confidence Interval (2-Sided) 95%
    12.248 to 67.387
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix + E2/NETA
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value for test of difference is by pooling the results from a logistic regression model including treatment as the main effect and baseline MBL volume as a covariate in each data set from multiple imputation.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 28.31
    Confidence Interval (2-Sided) 95%
    13.042 to 61.431
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in MBL Volume to the Final Month
    Description Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.
    Time Frame Baseline and Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants.
    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    Measure Participants 94 95 189
    Least Squares Mean (Standard Error) [mL]
    -4.3
    (15.44)
    -198.8
    (15.44)
    -168.8
    (10.72)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value for test of difference between each elagolix treatment group and placebo is by pooling the results from an ANCOVA model with treatment as the main effect and baseline MBL volume as a covariate in each dataset from multiple imputation.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean of Difference
    Estimated Value -194.5
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 21.70
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix + E2/NETA
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value for test of difference between each elagolix treatment group and placebo is by pooling the results from an ANCOVA model with treatment as the main effect and baseline MBL volume as a covariate in each dataset from multiple imputation.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean of Difference
    Estimated Value -164.6
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 18.87
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants With Suppression of Bleeding at the Final Month
    Description Suppression of bleeding is defined as having 0 days of bleeding (spotting is allowed) during the Final Month with the interval starting from Study Day 11. The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.
    Time Frame Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with an assessment
    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    Measure Participants 85 81 172
    Number [percentage of participants]
    4.7
    5%
    88.9
    93.6%
    61.0
    32.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value is calculated based on chi-square test (or Fisher's exact test if ≥ 20% of the cells have expected cell count < 5).
    Method chi-square or Fisher's exact test
    Comments
    Method of Estimation Estimation Parameter Between-Group Difference (%)
    Estimated Value 84.2
    Confidence Interval (2-Sided) 95%
    75.99 to 92.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix + E2/NETA
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value is calculated based on chi-square test (or Fisher's exact test if ≥ 20% of the cells have expected cell count < 5).
    Method chi-square or Fisher's exact test
    Comments
    Method of Estimation Estimation Parameter Between-Group Difference (%)
    Estimated Value 56.3
    Confidence Interval (2-Sided) 95%
    47.77 to 64.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in MBL Volume to Month 6
    Description Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.
    Time Frame Month 0 (Baseline), Month 6

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with an assessment at given time point.
    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    Measure Participants 64 53 124
    Least Squares Mean (Standard Error) [mL]
    28.5
    (16.68)
    -223.7
    (17.98)
    -198.1
    (11.89)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value is from mixed models repeated measures (MMRM) with treatment, month, and an interaction between treatment and month as fixed effect factors, and baseline MBL volume as a covariate comparing each elagolix treatment group with placebo.
    Method mixed model repeated measures
    Comments
    Method of Estimation Estimation Parameter LS Mean of Difference
    Estimated Value -252.3
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 24.53
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix + E2/NETA
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value is from mixed models repeated measures (MMRM) with treatment, month, and an interaction between treatment and month as fixed effect factors, and baseline MBL volume as a covariate comparing each elagolix treatment group with placebo.
    Method mixed model repeated measures
    Comments
    Method of Estimation Estimation Parameter LS Mean of Difference
    Estimated Value -226.6
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 20.50
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in MBL Volume to Month 3
    Description Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.
    Time Frame Month 0 (Baseline), Month 3

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with an assessment at given time point.
    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    Measure Participants 78 72 157
    Least Squares Mean (Standard Error) [mL]
    -14.2
    (11.57)
    -211.1
    (11.96)
    -200.3
    (8.17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value is from MMRM with treatment, month, and an interaction between treatment and month as fixed effect factors, and baseline MBL volume as a covariate comparing each elagolix treatment group with placebo.
    Method mixed model repeated measures
    Comments
    Method of Estimation Estimation Parameter LS Mean of Difference
    Estimated Value -196.9
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 16.66
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix + E2/NETA
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value is from MMRM with treatment, month, and an interaction between treatment and month as fixed effect factors, and baseline MBL volume as a covariate comparing each elagolix treatment group with placebo.
    Method mixed model repeated measures
    Comments
    Method of Estimation Estimation Parameter LS Mean of Difference
    Estimated Value -186.1
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 14.18
    Estimation Comments
    6. Secondary Outcome
    Title Percentage of Participants With Baseline Hemoglobin <= 10.5 g/dL Who Have an Increase in Hemoglobin > 2 g/dL at Month 6
    Description
    Time Frame Month 0 (Baseline), Month 6

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with baseline hemoglobin <= 10.5 g/dL and an assessment at Month 6.
    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    Measure Participants 24 25 48
    Number [percentage of participants]
    20.8
    22.1%
    40.0
    42.1%
    50.0
    26.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.146
    Comments The P value is calculated based on chi-square test (or Fisher's exact test if ≥ 20% of the cells have expected cell count < 5).
    Method chi-square or Fisher's exact test
    Comments
    Method of Estimation Estimation Parameter Between-Group Difference (%)
    Estimated Value 19.2
    Confidence Interval (2-Sided) 95%
    -5.99 to 44.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix + E2/NETA
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments The P value is calculated based on chi-square test (or Fisher's exact test if ≥ 20% of the cells have expected cell count < 5).
    Method chi-square or Fisher's exact test
    Comments
    Method of Estimation Estimation Parameter Between-Group Difference (%)
    Estimated Value 29.2
    Confidence Interval (2-Sided) 95%
    7.62 to 50.71
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Change From Baseline in MBL Volume to Month 1
    Description Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.
    Time Frame Month 0 (Baseline), Month 1

    Outcome Measure Data

    Analysis Population Description
    All randomized and treated participants with an assessment at given time point.
    Arm/Group Title Placebo Elagolix Elagolix + E2/NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    Measure Participants 88 83 175
    Least Squares Mean (Standard Error) [mL]
    -2.1
    (14.31)
    -196.6
    (14.74)
    -127.0
    (10.14)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value is from MMRM with treatment, month, and an interaction between treatment and month as fixed effect factors, and baseline MBL volume as a covariate comparing each elagolix treatment group with placebo.
    Method mixed model repeated measures
    Comments
    Method of Estimation Estimation Parameter LS Mean of Difference
    Estimated Value -194.5
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 20.56
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Elagolix + E2/NETA
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments The P value is from MMRM with treatment, month, and an interaction between treatment and month as fixed effect factors, and baseline MBL volume as a covariate comparing each elagolix treatment group with placebo.
    Method mixed model repeated measures
    Comments
    Method of Estimation Estimation Parameter LS Mean of Difference
    Estimated Value -125.0
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 17.55
    Estimation Comments

    Adverse Events

    Time Frame From first dose of study drug through 6 months of treatment with a 30-day follow-up period for participants who did not enroll in the extension study (Study M12-816). Mean (SD) treatment exposure was 160.3 (51.75), 155.2 (65.19), and 158.7 (54.68) days for the Placebo, Elagolix, and Elagolix and E2-NETA arms, respectively
    Adverse Event Reporting Description Treatment-emergent adverse events are presented.
    Arm/Group Title Placebo Elagolix Elagolix + E2-NETA
    Arm/Group Description Placebo for both elagolix BID and E2/NETA QD Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD Elagolix 300 mg BID and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD
    All Cause Mortality
    Placebo Elagolix Elagolix + E2-NETA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/94 (0%) 0/95 (0%) 0/189 (0%)
    Serious Adverse Events
    Placebo Elagolix Elagolix + E2-NETA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/94 (1.1%) 4/95 (4.2%) 7/189 (3.7%)
    Blood and lymphatic system disorders
    ANAEMIA 0/94 (0%) 0 0/95 (0%) 0 1/189 (0.5%) 1
    Endocrine disorders
    HYPERTHYROIDISM 0/94 (0%) 0 0/95 (0%) 0 1/189 (0.5%) 1
    Gastrointestinal disorders
    SMALL INTESTINAL OBSTRUCTION 0/94 (0%) 0 1/95 (1.1%) 1 0/189 (0%) 0
    Hepatobiliary disorders
    CHOLELITHIASIS 0/94 (0%) 0 1/95 (1.1%) 1 1/189 (0.5%) 1
    Infections and infestations
    APPENDICITIS 0/94 (0%) 0 1/95 (1.1%) 1 0/189 (0%) 0
    CELLULITIS 0/94 (0%) 0 0/95 (0%) 0 1/189 (0.5%) 1
    Metabolism and nutrition disorders
    OBESITY 0/94 (0%) 0 0/95 (0%) 0 1/189 (0.5%) 1
    Pregnancy, puerperium and perinatal conditions
    ABORTION COMPLETE 1/94 (1.1%) 1 0/95 (0%) 0 0/189 (0%) 0
    Psychiatric disorders
    ANXIETY 0/94 (0%) 0 0/95 (0%) 0 1/189 (0.5%) 1
    Reproductive system and breast disorders
    DYSFUNCTIONAL UTERINE BLEEDING 0/94 (0%) 0 0/95 (0%) 0 1/189 (0.5%) 1
    DYSMENORRHOEA 0/94 (0%) 0 0/95 (0%) 0 1/189 (0.5%) 1
    MENORRHAGIA 0/94 (0%) 0 0/95 (0%) 0 1/189 (0.5%) 1
    PELVIC PAIN 0/94 (0%) 0 1/95 (1.1%) 1 0/189 (0%) 0
    Other (Not Including Serious) Adverse Events
    Placebo Elagolix Elagolix + E2-NETA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 34/94 (36.2%) 58/95 (61.1%) 80/189 (42.3%)
    Gastrointestinal disorders
    NAUSEA 9/94 (9.6%) 11 4/95 (4.2%) 4 14/189 (7.4%) 15
    General disorders
    FATIGUE 5/94 (5.3%) 5 3/95 (3.2%) 3 10/189 (5.3%) 10
    Infections and infestations
    NASOPHARYNGITIS 8/94 (8.5%) 9 4/95 (4.2%) 4 10/189 (5.3%) 11
    URINARY TRACT INFECTION 5/94 (5.3%) 6 2/95 (2.1%) 2 12/189 (6.3%) 12
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 2/94 (2.1%) 2 5/95 (5.3%) 5 9/189 (4.8%) 10
    Nervous system disorders
    HEADACHE 5/94 (5.3%) 6 13/95 (13.7%) 14 20/189 (10.6%) 21
    Psychiatric disorders
    LIBIDO DECREASED 2/94 (2.1%) 2 3/95 (3.2%) 3 10/189 (5.3%) 10
    MOOD SWINGS 2/94 (2.1%) 2 6/95 (6.3%) 6 6/189 (3.2%) 8
    Reproductive system and breast disorders
    DYSMENORRHOEA 6/94 (6.4%) 6 0/95 (0%) 0 6/189 (3.2%) 6
    Skin and subcutaneous tissue disorders
    NIGHT SWEATS 5/94 (5.3%) 6 24/95 (25.3%) 24 20/189 (10.6%) 21
    Vascular disorders
    HOT FLUSH 4/94 (4.3%) 4 41/95 (43.2%) 41 37/189 (19.6%) 37

    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:
    NCT02691494
    Other Study ID Numbers:
    • M12-817
    First Posted:
    Feb 25, 2016
    Last Update Posted:
    Jul 13, 2021
    Last Verified:
    Jul 1, 2021