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    Clinical Trial Results:
    Extension Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Subjects with Moderate to Severe Endometriosis-Associated Pain

    Summary
    EudraCT number
    		 2013-001047-31
    Trial protocol
    		 CZ   GB   AT   IT   ES   HU  
    Global end of trial date
    23 May 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Jun 2018
    First version publication date
    06 Jun 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    M12-821
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02143713
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Abbvie Deutschland GmbH & Co.KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Global Medical Services, Abbvie, 011 800-633-9110,
    Scientific contact
    Michael Snabes, Abbvie, michael.snabes@abbvie.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 May 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 May 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objectives of this study were to evaluate the long-term safety and efficacy of elagolix for the management of moderate to severe endometriosis-associated pain in subjects administered elagolix for up to 12 months (initial 6 months if on active treatment in pivotal Study M12-671 and an additional 6 months in this extension study).
    Protection of trial subjects
    All subjects entering the study had to sign an informed consent that was explained to them and questions encouraged.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 May 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    Austria: 2
    Country: Number of subjects enrolled
    Brazil: 16
    Country: Number of subjects enrolled
    Czech Republic: 41
    Country: Number of subjects enrolled
    Hungary: 20
    Country: Number of subjects enrolled
    Italy: 33
    Country: Number of subjects enrolled
    New Zealand: 15
    Country: Number of subjects enrolled
    Poland: 105
    Country: Number of subjects enrolled
    South Africa: 9
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    United Kingdom: 8
    Country: Number of subjects enrolled
    United States: 225
    Worldwide total number of subjects
    495
    EEA total number of subjects
    216
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    495
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants who completed the 6-month Treatment Period in the pivotal Study M12-671 (NCT01931670) could enter this extension study. The study was conducted at 148 sites in North and South America, Europe, Australia/New Zealand, and South Africa. One patient was enrolled but did not receive study drug and is not included in the results.

    Pre-assignment
    Screening details
    		 The study consisted of a 6-month Treatment Period and a Post-treatment Follow-up (PTFU) of up to 12 months. Participants who received elagolix in the pivotal study continued to receive the same dose for a further 6 months; participants on placebo in the pivotal study were randomized 1:1 to either elagolix 150 mg once daily or 200 mg twice daily.

    Period 1
    Period 1 title
    Treatment Period (6 Months) (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Elagolix 150 mg QD
    Arm description
    		 Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg once daily (QD) for 6 months in this extension Study M12-821.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Elagolix
    Investigational medicinal product code
    ABT-620
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Elagolix tablets administered orally

    Arm title
    		 Placebo/Elagolix 200 mg BID
    Arm description
    		 Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg twice a day (BID) for 6 months in this extension Study M12-821.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Elagolix
    Investigational medicinal product code
    ABT-620
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Elagolix tablets administered orally

    Arm title
    		 Elagolix/Elagolix 150 mg QD
    Arm description
    		 Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Elagolix
    Investigational medicinal product code
    ABT-620
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Elagolix tablets administered orally

    Arm title
    		 Elagolix/Elagolix 200 mg BID
    Arm description
    		 Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Elagolix
    Investigational medicinal product code
    ABT-620
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Elagolix tablets administered orally

    Number of subjects in period 1
    		Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Started
    102
    111
    142
    140
    Completed
    82
    99
    120
    112
    Not completed
    20
    12
    22
    28
         Exclusionary medication
    2
    -
    -
    -
         Consent withdrawn by subject
    1
    2
    5
    4
         Surgery or invasive intervention
    2
    -
    -
    2
         Other
    3
    -
    3
    2
         Pregnancy
    -
    2
    2
    -
         Adverse event
    7
    8
    8
    9
         Non-compliance
    1
    -
    -
    3
         Bone mineral density decrease
    -
    -
    -
    4
         Lost to follow-up
    3
    -
    4
    3
         Lack of efficacy
    1
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo/Elagolix 150 mg QD
    Reporting group description
    		 Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg once daily (QD) for 6 months in this extension Study M12-821.

    Reporting group title
    Placebo/Elagolix 200 mg BID
    Reporting group description
    		 Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg twice a day (BID) for 6 months in this extension Study M12-821.

    Reporting group title
    Elagolix/Elagolix 150 mg QD
    Reporting group description
    		 Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.

    Reporting group title
    Elagolix/Elagolix 200 mg BID
    Reporting group description
    		 Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.

    Reporting group values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID Total
    Number of subjects
    		 102 111 142 140 495
    Age categorical
    Units: Subjects
        18 - 65 years
    		 102 111 142 140 495
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 33.5 ± 7.00 33.2 ± 6.32 33.2 ± 7.02 34.1 ± 6.70 -
    Gender categorical
    Units: Subjects
        Female
    		 102 111 142 140 495
        Male
    		 0 0 0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 14 11 15 21 61
        Not Hispanic or Latino
    		 88 100 127 119 434
    Race
    Units: Subjects
        White
    		 94 100 127 126 447
        Black or African American
    		 7 9 14 12 42
        Asian
    		 0 1 1 1 3
        Multi race
    		 0 1 0 1 2
        Native Hawaiian or other Pacific Islander
    		 1 0 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Placebo/Elagolix 150 mg QD
    Reporting group description
    		 Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg once daily (QD) for 6 months in this extension Study M12-821.

    Reporting group title
    Placebo/Elagolix 200 mg BID
    Reporting group description
    		 Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg twice a day (BID) for 6 months in this extension Study M12-821.

    Reporting group title
    Elagolix/Elagolix 150 mg QD
    Reporting group description
    		 Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.

    Reporting group title
    Elagolix/Elagolix 200 mg BID
    Reporting group description
    		 Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.

    Primary: Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment

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    End point title
    		 Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment [1]
    End point description
    Response was defined as a reduction of -0.85 or more from baseline in dysmenorrhea (pain during menstruation) as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a < 15% increase in average rescue analgesic pill count and no additional analgesic). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic use for endometriosis-associated pain daily and dysmenorrhea and its impact on daily activities each day of their period in an electronic diary (e-Diary). Dysmenorrhea was assessed according to the following: • 0: No discomfort • 1: Mild discomfort but I was easily able to do the things I usually do • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do • 3: Severe pain that made it difficult to do the things I usually do. Analgesic use and pain scores were averaged over the 35 days prior to each visit.
    End point type
    Primary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparisons between dose groups were not prespecified and not performed since the extension studies were not designed or powered for these analyses.
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    81 [2]
    98 [3]
    122 [4]
    116 [5]
    Units: percentage of participants
        number (not applicable)
    37.0
    57.1
    50.8
    75.9
    Notes
    [2] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [3] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [4] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [5] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    No statistical analyses for this end point

    Primary: Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment

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    End point title
    		 Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment [6]
    End point description
    Response was defined as a reduction of −0.43 or greater from baseline for non-menstrual pelvic pain as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a < 15% increase in average pill count of rescue analgesics and no additional analgesics). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed non-menstrual pelvic pain and its impact on their daily activities each day in an e-Diary according to the following response options: • 0: No discomfort • 1: Mild discomfort but I was easily able to do the things I usually do • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do • 3: Severe pain that made it difficult to do the things I usually do. Pain scores and analgesic use were averaged over the 35 days prior to each visit.
    End point type
    Primary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparisons between dose groups were not prespecified and not performed since the extension studies were not designed or powered for these analyses.
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    81 [7]
    98 [8]
    122 [9]
    116 [10]
    Units: percentage of participants
        number (not applicable)
    27.2
    32.7
    66.4
    67.2
    Notes
    [7] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [8] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [9] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [10] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment

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    End point title
    		 Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment
    End point description
    Response was defined as a reduction of -0.85 or more from baseline in dysmenorrhea (pain during menstruation) as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a < 15% increase in average rescue analgesic pill count and no additional analgesic). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic use for endometriosis-associated pain daily and dysmenorrhea and its impact on daily activities each day of their period in an electronic diary (e-Diary). Dysmenorrhea was assessed according to the following: • 0: No discomfort • 1: Mild discomfort but I was easily able to do the things I usually do • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do • 3: Severe pain that made it difficult to do the things I usually do. Analgesic use and pain scores were averaged over the 35 days prior to each visit.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102 [11]
    111 [12]
    142 [13]
    140 [14]
    Units: percentage of participants
    number (not applicable)
        Month 1 (N = 102, 110, 141, 140)
    11.8
    24.5
    56.7
    74.3
        Month 2 (N = 96, 106, 136, 134)
    36.5
    62.3
    52.2
    79.1
        Month 3 (N = 90, 103, 133, 131)
    30.0
    64.1
    48.1
    77.1
        Month 4 (N = 88, 102, 128, 125)
    33.0
    64.7
    47.7
    80.0
        Month 5 (N = 81, 100, 126, 117)
    30.9
    59.0
    53.2
    82.9
    Notes
    [11] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [12] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [13] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [14] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment

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    End point title
    		 Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment
    End point description
    Response was defined as a reduction of −0.43 or greater from baseline for non-menstrual pelvic pain as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a < 15% increase in average pill count of rescue analgesics and no additional analgesics). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed non-menstrual pelvic pain and its impact on their daily activities each day in an e-Diary according to the following response options: • 0: No discomfort • 1: Mild discomfort but I was easily able to do the things I usually do • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do • 3: Severe pain that made it difficult to do the things I usually do. Pain scores and analgesic use were averaged over the 35 days prior to each visit.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102 [15]
    111 [16]
    142 [17]
    140 [18]
    Units: percentage of participants
    number (not applicable)
        Month 1 (N = 102, 110, 141, 140)
    12.7
    18.2
    61.7
    62.1
        Month 2 (N = 96, 106, 136, 134)
    20.8
    27.4
    61.8
    63.4
        Month 3 (N = 90, 103, 133, 131)
    18.9
    29.1
    66.2
    65.6
        Month 4 (N = 88, 102, 128, 125)
    27.3
    34.3
    64.8
    66.4
        Month 5 (N = 81, 100, 126, 117)
    28.4
    33.0
    67.5
    72.6
    Notes
    [15] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [16] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [17] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [18] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment

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    End point title
    		 Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment
    End point description
    Response was defined as a reduction of −0.29 or more from baseline in dyspareunia (pain during sexual intercourse) as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a < 15% increase in average rescue analgesic pill count and no additional analgesics). Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed dyspareunia each day in an e-Diary. Dyspareunia was assessed according to the following: • 0: None; No discomfort during sexual intercourse • 1: Mild; Able to tolerate the discomfort during sexual intercourse • 2: Moderate; Intercourse was interrupted due to pain • 3: Severe; Avoided intercourse because of pain • Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse. Pain scores and analgesic use were averaged over the 35 days prior to each visit. Responses of "Not Applicable" were excluded.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102 [19]
    111 [20]
    142 [21]
    140 [22]
    Units: percentage of participants
    number (not applicable)
        Month 1 (N = 78, 77, 101, 93)
    23.1
    27.3
    50.5
    63.4
        Month 2 (N = 72, 77, 100, 95)
    30.6
    35.1
    47.0
    65.3
        Month 3 (N = 67, 72, 97, 85)
    37.3
    33.3
    55.7
    61.2
        Month 4 (N = 66, 65, 98, 83)
    34.8
    32.3
    54.1
    60.2
        Month 5 (N = 60, 65, 86, 74)
    30.0
    40.0
    52.3
    63.5
        Month 6 (N = 59, 67, 85, 74)
    28.8
    31.3
    45.9
    58.1
    Notes
    [19] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [20] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [21] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [22] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Dyspareunia Based on Daily Assessment

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    End point title
    		 Percent Change From Baseline in Dyspareunia Based on Daily Assessment
    End point description
    Participants assessed dyspareunia each day in an e-Diary according to the following response options: • 0: None; No discomfort during sexual intercourse • 1: Mild; Able to tolerate the discomfort during sexual intercourse • 2: Moderate; Intercourse was interrupted due to pain • 3: Severe; Avoided intercourse because of pain • Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse. Pain scores were averaged over the 35 days prior to each visit. Responses of "Not Applicable" were excluded.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    83 [23]
    87 [24]
    118 [25]
    108 [26]
    Units: percent change
    arithmetic mean (standard deviation)
        Month 1 (N = 63, 64, 95, 87)
    -10.4 ± 52.31
    -16.9 ± 59.04
    -43.7 ± 64.77
    -48.7 ± 66.94
        Month 2 (N = 60, 64, 93, 89)
    -12.0 ± 51.80
    -19.2 ± 65.67
    -38.0 ± 74.89
    -51.1 ± 52.74
        Month 3 (N = 54, 62, 91, 78)
    -22.1 ± 46.07
    -26.4 ± 69.18
    -43.4 ± 55.71
    -49.1 ± 46.47
        Month 4 (N = 53, 57, 93, 77)
    -22.3 ± 51.64
    -12.6 ± 141.47
    -49.1 ± 48.27
    -48.5 ± 56.42
        Month 5 (N = 48, 55, 80, 68)
    -25.7 ± 45.51
    -9.5 ± 191.05
    -57.0 ± 43.57
    -42.7 ± 64.12
        Month 6 (N = 46, 55, 79, 69)
    -18.8 ± 54.07
    -28.3 ± 53.62
    -51.3 ± 45.87
    -49.7 ± 54.23
    Notes
    [23] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [24] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [25] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [26] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment

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    End point title
    		 Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment
    End point description
    Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities each day of their period in an e-Diary according to the following response options: • 0: No discomfort • 1: Mild discomfort but I was easily able to do the things I usually do • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do • 3: Severe pain that made it difficult to do the things I usually do. Pain scores were averaged over the 35 days prior to each visit.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102 [27]
    111 [28]
    142 [29]
    140 [30]
    Units: percent change
    arithmetic mean (standard deviation)
        Month 1 (N = 98, 108, 141, 140)
    -18.4 ± 41.71
    -27.0 ± 55.50
    -54.6 ± 41.79
    -81.3 ± 36.00
        Month 2 (N = 92, 104, 136, 134)
    -47.6 ± 50.17
    -70.2 ± 55.81
    -50.7 ± 41.16
    -84.0 ± 33.76
        Month 3 (N = 86, 101, 133, 131)
    -40.2 ± 51.63
    -76.7 ± 48.73
    -49.0 ± 41.98
    -84.8 ± 32.01
        Month 4 (N = 84, 100, 128, 125)
    -40.3 ± 51.25
    -77.5 ± 41.25
    -50.5 ± 39.97
    -83.0 ± 36.23
        Month 5 (N = 78, 98, 126, 117)
    -38.0 ± 50.01
    -75.6 ± 47.88
    -51.8 ± 39.25
    -82.7 ± 33.89
        Month 6 (N = 78, 96, 122, 116)
    -44.6 ± 45.08
    -80.7 ± 38.43
    -52.9 ± 39.52
    -81.8 ± 33.57
    Notes
    [27] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [28] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [29] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [30] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment

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    End point title
    		 Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment
    End point description
    Participants assessed non-menstrual pelvic pain and its impact on their daily activities each day in an e-Diary according to the following response options: • 0: No discomfort • 1: Mild discomfort but I was easily able to do the things I usually do • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do • 3: Severe pain that made it difficult to do the things I usually do. Pain scores were averaged over the 35 days prior to each visit.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102 [31]
    111 [32]
    142 [33]
    140 [34]
    Units: percent change
    arithmetic mean (standard deviation)
        Month 1 (N = 98, 107, 141, 140)
    -7.3 ± 57.59
    -11.3 ± 64.29
    -47.9 ± 39.03
    -54.0 ± 41.77
        Month 2 (N = 92, 103, 136, 134)
    -7.8 ± 71.50
    -12.8 ± 143.81
    -48.6 ± 38.70
    -53.1 ± 42.04
        Month 3 (N = 86, 100, 133, 131)
    -24.5 ± 53.77
    -17.8 ± 130.92
    -50.7 ± 38.41
    -54.5 ± 41.70
        Month 4 (N = 84, 99, 128, 125)
    -25.0 ± 53.14
    -23.1 ± 123.65
    -53.2 ± 37.47
    -54.4 ± 40.89
        Month 5 (N = 77, 97, 126, 117)
    -30.4 ± 44.88
    -31.2 ± 113.03
    -54.9 ± 39.53
    -57.4 ± 42.84
        Month 6 (N = 77, 95, 122, 116)
    -24.0 ± 62.40
    -27.2 ± 164.50
    -53.6 ± 40.41
    -55.9 ± 41.01
    Notes
    [31] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [32] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [33] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    [34] - Subjects who received at least 1 dose of study drug in Study M12-821 with available data
    No statistical analyses for this end point

    Secondary: Change From Baseline in Any Rescue Analgesic Use

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    End point title
    		 Change From Baseline in Any Rescue Analgesic Use
    End point description
    Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. Any rescue analgesic use (NSAID and/or opioid) was calculated as the total number of pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102
    111
    142
    140
    Units: pills/day
    arithmetic mean (standard deviation)
        Month 1 (N = 102, 110, 141, 140)
    -0.07 ± 0.320
    -0.16 ± 0.389
    -0.44 ± 0.745
    -0.47 ± 0.711
        Month 2 (N = 96, 106, 136, 134)
    -0.16 ± 0.375
    -0.24 ± 0.510
    -0.49 ± 0.829
    -0.52 ± 0.774
        Month 3 (N = 90, 103, 133, 131)
    -0.14 ± 0.391
    -0.24 ± 0.524
    -0.46 ± 0.806
    -0.53 ± 0.774
        Month 4 (N = 88, 102, 128, 125)
    -0.13 ± 0.460
    -0.28 ± 0.483
    -0.48 ± 0.815
    -0.54 ± 0.811
        Month 5 (N = 81, 100, 126, 117)
    -0.16 ± 0.446
    -0.29 ± 0.539
    -0.46 ± 0.817
    -0.57 ± 0.758
        Month 6 (N = 81, 98, 122, 116)
    -0.16 ± 0.410
    -0.28 ± 0.513
    -0.45 ± 0.834
    -0.59 ± 0.799
    No statistical analyses for this end point

    Secondary: Change From Baseline in NSAID Rescue Analgesic Use

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    End point title
    		 Change From Baseline in NSAID Rescue Analgesic Use
    End point description
    Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. NSAID rescue analgesic use was calculated as the total number of NSAID pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102
    111
    142
    140
    Units: pills/day
    arithmetic mean (standard deviation)
        Month 1 (N = 102, 110, 141, 140)
    -0.05 ± 0.209
    -0.12 ± 0.263
    -0.25 ± 0.590
    -0.28 ± 0.363
        Month 2 (N = 96, 106, 136, 134)
    -0.10 ± 0.271
    -0.18 ± 0.343
    -0.29 ± 0.624
    -0.29 ± 0.389
        Month 3 (N = 90, 103, 133, 131)
    -0.11 ± 0.281
    -0.18 ± 0.336
    -0.27 ± 0.550
    -0.30 ± 0.370
        Month 4 (N = 88, 102, 128, 125)
    -0.09 ± 0.297
    -0.20 ± 0.334
    -0.28 ± 0.531
    -0.30 ± 0.379
        Month 5 (N = 81, 100, 126, 117)
    -0.11 ± 0.316
    -0.21 ± 0.353
    -0.27 ± 0.556
    -0.31 ± 0.376
        Month 6 (N = 81, 98, 122, 116)
    -0.10 ± 0.241
    -0.20 ± 0.369
    -0.26 ± 0.569
    -0.32 ± 0.380
    No statistical analyses for this end point

    Secondary: Change From Baseline in Opioid Rescue Analgesic Use

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    End point title
    		 Change From Baseline in Opioid Rescue Analgesic Use
    End point description
    Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. Opioid rescue analgesic use was calculated as the total number of opioid pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102
    111
    142
    140
    Units: pills/day
    arithmetic mean (standard deviation)
        Month 1 (N = 102, 110, 141, 140)
    -0.02 ± 0.197
    -0.04 ± 0.243
    -0.19 ± 0.526
    -0.20 ± 0.596
        Month 2 (N = 96, 106, 136, 134)
    -0.06 ± 0.214
    -0.06 ± 0.270
    -0.19 ± 0.573
    -0.23 ± 0.655
        Month 3 (N = 90, 103, 133, 131)
    -0.04 ± 0.217
    -0.06 ± 0.309
    -0.19 ± 0.613
    -0.23 ± 0.662
        Month 4 (N = 88, 102, 128, 125)
    -0.05 ± 0.262
    -0.08 ± 0.231
    -0.20 ± 0.620
    -0.24 ± 0.693
        Month 5 (N = 81, 100, 126, 117)
    -0.05 ± 0.227
    -0.08 ± 0.273
    -0.19 ± 0.613
    -0.26 ± 0.643
        Month 6 (N = 81, 98, 122, 116)
    -0.06 ± 0.237
    -0.07 ± 0.271
    -0.20 ± 0.623
    -0.27 ± 0.680
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS)

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    End point title
    		 Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS)
    End point description
    The NRS measured endometriosis-associated pain with and without menstruation on an 11-point scale from 0 = no pain to 10 = worst pain ever. Participants were asked to assess their endometriosis pain over the past 24 hours at it's worst at approximately the same time every day in the e-Diary. Pain scores were averaged over the 35 days prior to each visit.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102
    111
    142
    140
    Units: percent change
    arithmetic mean (standard deviation)
        Month 1 (N = 102, 110, 141, 140)
    -12.0 ± 44.71
    -18.2 ± 51.75
    -50.8 ± 36.58
    -58.7 ± 37.07
        Month 2 (N = 96, 106, 136, 134)
    -20.7 ± 40.87
    -25.8 ± 87.35
    -50.7 ± 36.08
    -58.7 ± 36.31
        Month 3 (N = 90, 103, 133, 131)
    -27.7 ± 39.61
    -35.0 ± 65.06
    -52.7 ± 36.40
    -59.5 ± 35.99
        Month 4 (N = 88, 102, 128, 125)
    -31.2 ± 43.28
    -38.8 ± 58.04
    -54.7 ± 33.26
    -60.4 ± 34.77
        Month 5 (N = 81, 100, 126, 117)
    -29.2 ± 52.99
    -45.6 ± 60.86
    -56.1 ± 35.81
    -62.3 ± 34.99
        Month 6 (N = 81, 98, 122, 116)
    -30.7 ± 42.08
    -41.7 ± 83.80
    -53.9 ± 35.06
    -61.1 ± 33.71
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved

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    End point title
    		 Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved
    End point description
    The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories: 1. Very Much Improved 2. Much Improved 3. Minimally Improved 4. Not Changed 5. Minimally Worse 6. Much Worse 7. Very Much Worse
    End point type
    Secondary
    End point timeframe
    Months 1, 2, 3, 4, 5, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102
    111
    142
    140
    Units: percentage of participants
    number (not applicable)
        Month 1 (N = 98, 111, 137, 138)
    50.0
    56.8
    65.7
    78.3
        Month 2 (N = 92, 106, 136, 133)
    58.7
    74.5
    69.1
    78.9
        Month 3 (N = 88, 103, 131, 127)
    63.6
    70.9
    67.9
    77.2
        Month 4 (N = 88, 101, 128, 123)
    61.4
    75.2
    71.1
    82.1
        Month 5 (N = 82, 100, 124, 117)
    67.1
    81.0
    71.8
    82.1
        Month 6 (N = 76, 93, 114, 106)
    65.8
    76.3
    75.4
    84.0
    No statistical analyses for this end point

    Secondary: Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension

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    End point title
    		 Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension
    End point description
    The EHP-30 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-30 consists of two parts: a core questionnaire containing 5 scales that are applicable to all women with endometriosis and includes pain, control and powerlessness, emotional well-being, social support, and self-image, and a modular part containing 6 scales which do not necessarily apply to all women with endometriosis. Each question in the core questionnaire is scored on the following scale: 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Always. The pain dimension consists of 11 questions. The dimension score ranges from 0 to 100, where 0 = best possible health status as measured by the questionnaire; 100 = worst possible health status. A negative change from baseline score indicates improvement in quality of life.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 3, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102
    111
    142
    140
    Units: units on a scale
    arithmetic mean (standard deviation)
        Month 1 (N = 98, 111, 136, 138)
    -8.02 ± 17.828
    -12.18 ± 17.465
    -32.25 ± 21.235
    -36.45 ± 22.320
        Month 3 (N = 92, 104, 136, 129)
    -11.12 ± 22.424
    -15.25 ± 21.467
    -32.00 ± 23.172
    -37.42 ± 21.492
        Month 6 (N = 74, 92, 110, 100)
    -10.60 ± 20.827
    -15.61 ± 21.047
    -32.95 ± 23.674
    -38.48 ± 21.924
    No statistical analyses for this end point

    Secondary: Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension

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    End point title
    		 Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension
    End point description
    The EHP-30 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-30 consists of two parts: a core questionnaire containing 5 scales that are applicable to all women with endometriosis and a modular part containing 6 scales which do not necessarily apply to all women with endometriosis; only 1 modular questionnaire (sexual intercourse [5 items]) was used in this study. The Sexual Intercourse dimension consists of 5 questions, each answered on the following scale: 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Always, or Not Applicable (not scored). The dimension score ranges from 0 to 100, where 0 = best possible health status as measured by the questionnaire; 100 = worst possible health status. A negative change from baseline score indicates improvement in quality of life.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 3, and 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    90
    97
    109
    111
    Units: units on a scale
    arithmetic mean (standard deviation)
        Month 1 (N = 79, 71, 90, 98)
    -3.29 ± 13.655
    -10.35 ± 16.846
    -24.17 ± 26.010
    -28.37 ± 29.886
        Month 3 (n = 68, 64, 90, 86)
    -9.26 ± 20.264
    -12.50 ± 22.449
    -24.61 ± 26.986
    -28.66 ± 31.580
        Month 6 (N = 55, 63, 78, 67)
    -9.36 ± 19.294
    -7.30 ± 22.963
    -23.21 ± 26.310
    -33.21 ± 31.988
    No statistical analyses for this end point

    Secondary: Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household

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    End point title
    		 Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household
    End point description
    The HRPQ consists of 9 questions measuring the impact of endometriosis-associated pain and its treatment on work productivity and daily activities in the home. Absenteeism: Number of hours of intended work lost due to illness or treatment. Presenteeism: Number of hours of work where output was impacted by illness or treatments. Total hours lost is the sum of hours missed due to absenteeism plus presenteeism.
    End point type
    Secondary
    End point timeframe
    Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    91
    102
    126
    130
    Units: hours
    arithmetic mean (standard deviation)
        Absenteeism from workplace (N = 49, 67, 77, 72)
    -2.82 ± 5.648
    -1.33 ± 8.945
    -1.25 ± 4.377
    -1.73 ± 4.133
        Presenteeism from workplace (N = 48, 67, 76, 68)
    -10.31 ± 15.902
    -8.37 ± 9.675
    -8.38 ± 12.489
    -10.63 ± 9.837
        Total hours lost from workplace (N=49, 67, 77, 72)
    -13.22 ± 16.663
    -9.70 ± 13.683
    -9.36 ± 13.365
    -12.02 ± 10.447
        Absenteeism from household (N = 58, 71, 88, 88)
    -3.17 ± 6.241
    -2.68 ± 3.779
    -3.56 ± 4.924
    -3.50 ± 4.180
        Presenteeism from household (N = 58, 71, 86, 84)
    -2.47 ± 6.581
    -2.19 ± 4.973
    -2.33 ± 5.182
    -2.74 ± 5.308
        Total hours lost from household (N=58, 71, 88, 88)
    -5.64 ± 9.919
    -4.86 ± 7.185
    -5.84 ± 7.844
    -6.17 ± 7.930
    No statistical analyses for this end point

    Secondary: Number of Participants With Non-study Health Visits During the Treatment Period

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    End point title
    		 Number of Participants With Non-study Health Visits During the Treatment Period
    End point description
    The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    102
    111
    142
    140
    Units: participants
    48
    65
    76
    76
    No statistical analyses for this end point

    Secondary: Number of Days in Hospital During the Treatment Period

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    End point title
    		 Number of Days in Hospital During the Treatment Period
    End point description
    The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study, including physician visits, hospitalizations and types of procedures received.
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Number of subjects analysed
    9 [35]
    11 [36]
    10 [37]
    13 [38]
    Units: days
        median (full range (min-max))
    2.0 (1 to 6)
    4.0 (2 to 13)
    3.0 (1 to 7)
    3.0 (1 to 7)
    Notes
    [35] - Subjects who received at least 1 dose of study drug in Study M12-821 and underwent hospitalization
    [36] - Subjects who received at least 1 dose of study drug in Study M12-821 and underwent hospitalization
    [37] - Subjects who received at least 1 dose of study drug in Study M12-821 and underwent hospitalization
    [38] - Subjects who received at least 1 dose of study drug in Study M12-821 and underwent hospitalization
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Placebo/Elagolix 150 mg QD
    Reporting group description
    		 Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.

    Reporting group title
    Placebo/Elagolix 200 mg BID
    Reporting group description
    		 Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.

    Reporting group title
    Elagolix/Elagolix 150 mg QD
    Reporting group description
    		 Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.

    Reporting group title
    Elagolix/Elagolix 200 mg BID
    Reporting group description
    		 Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.

    Serious adverse events
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 102 (3.92%)
    8 / 111 (7.21%)
    7 / 142 (4.93%)
    8 / 140 (5.71%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    PELVIC NEOPLASM
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TERATOMA
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    CARBON MONOXIDE POISONING
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INCISIONAL HERNIA
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LIGAMENT RUPTURE
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PROCEDURAL HYPERTENSION
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TIBIA FRACTURE
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    ABORTION INDUCED
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    2 / 142 (1.41%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    ABORTION SPONTANEOUS
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL HERNIA
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    2 / 102 (1.96%)
    0 / 111 (0.00%)
    1 / 142 (0.70%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN LOWER
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL MOTILITY DISORDER
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IRRITABLE BOWEL SYNDROME
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    OVARIAN CYST
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PELVIC PAIN
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    1 / 142 (0.70%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERINEAL PAIN
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLELITHIASIS
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NASAL POLYPS
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 102 (0.98%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OSTEOCHONDROSIS
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    DENGUE FEVER
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    0 / 102 (0.00%)
    1 / 111 (0.90%)
    0 / 142 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE WOUND INFECTION
         subjects affected / exposed
    0 / 102 (0.00%)
    0 / 111 (0.00%)
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo/Elagolix 150 mg QD Placebo/Elagolix 200 mg BID Elagolix/Elagolix 150 mg QD Elagolix/Elagolix 200 mg BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    49 / 102 (48.04%)
    74 / 111 (66.67%)
    65 / 142 (45.77%)
    70 / 140 (50.00%)
    Investigations
    BONE DENSITY DECREASED
         subjects affected / exposed
    1 / 102 (0.98%)
    2 / 111 (1.80%)
    0 / 142 (0.00%)
    8 / 140 (5.71%)
         occurrences all number
    1
    2
    0
    8
    Vascular disorders
    HOT FLUSH
         subjects affected / exposed
    15 / 102 (14.71%)
    45 / 111 (40.54%)
    7 / 142 (4.93%)
    11 / 140 (7.86%)
         occurrences all number
    16
    47
    7
    11
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    13 / 102 (12.75%)
    18 / 111 (16.22%)
    9 / 142 (6.34%)
    9 / 140 (6.43%)
         occurrences all number
    15
    20
    11
    9
    General disorders and administration site conditions
    FATIGUE
         subjects affected / exposed
    0 / 102 (0.00%)
    6 / 111 (5.41%)
    0 / 142 (0.00%)
    2 / 140 (1.43%)
         occurrences all number
    0
    6
    0
    2
    Gastrointestinal disorders
    NAUSEA
         subjects affected / exposed
    6 / 102 (5.88%)
    13 / 111 (11.71%)
    14 / 142 (9.86%)
    5 / 140 (3.57%)
         occurrences all number
    6
    14
    15
    5
    Reproductive system and breast disorders
    AMENORRHOEA
         subjects affected / exposed
    4 / 102 (3.92%)
    14 / 111 (12.61%)
    4 / 142 (2.82%)
    2 / 140 (1.43%)
         occurrences all number
    6
    16
    4
    2
    Skin and subcutaneous tissue disorders
    ACNE
         subjects affected / exposed
    6 / 102 (5.88%)
    6 / 111 (5.41%)
    5 / 142 (3.52%)
    2 / 140 (1.43%)
         occurrences all number
    6
    6
    6
    2
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    3 / 102 (2.94%)
    7 / 111 (6.31%)
    4 / 142 (2.82%)
    2 / 140 (1.43%)
         occurrences all number
    3
    7
    5
    2
    INSOMNIA
         subjects affected / exposed
    4 / 102 (3.92%)
    8 / 111 (7.21%)
    4 / 142 (2.82%)
    3 / 140 (2.14%)
         occurrences all number
    4
    8
    4
    3
    MOOD SWINGS
         subjects affected / exposed
    7 / 102 (6.86%)
    7 / 111 (6.31%)
    3 / 142 (2.11%)
    2 / 140 (1.43%)
         occurrences all number
    7
    7
    3
    2
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    9 / 102 (8.82%)
    12 / 111 (10.81%)
    6 / 142 (4.23%)
    9 / 140 (6.43%)
         occurrences all number
    10
    13
    6
    10
    BACK PAIN
         subjects affected / exposed
    2 / 102 (1.96%)
    6 / 111 (5.41%)
    6 / 142 (4.23%)
    10 / 140 (7.14%)
         occurrences all number
    2
    7
    6
    11
    Infections and infestations
    NASOPHARYNGITIS
         subjects affected / exposed
    6 / 102 (5.88%)
    10 / 111 (9.01%)
    6 / 142 (4.23%)
    9 / 140 (6.43%)
         occurrences all number
    6
    10
    6
    10
    SINUSITIS
         subjects affected / exposed
    6 / 102 (5.88%)
    6 / 111 (5.41%)
    8 / 142 (5.63%)
    8 / 140 (5.71%)
         occurrences all number
    6
    8
    9
    8
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    5 / 102 (4.90%)
    6 / 111 (5.41%)
    6 / 142 (4.23%)
    6 / 140 (4.29%)
         occurrences all number
    6
    7
    8
    7
    URINARY TRACT INFECTION
         subjects affected / exposed
    3 / 102 (2.94%)
    9 / 111 (8.11%)
    10 / 142 (7.04%)
    11 / 140 (7.86%)
         occurrences all number
    3
    12
    11
    13

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Sep 2014
    The purpose of this amendment was to: ● Update the Treatment Period to add: "Prophylactic use of rescue analgesics (i.e., on a standing basis or for prevention of pain) for endometriosis-associated pain is not permitted during the study (from Day 1 of the Treatment Period through Month 6 of the Post-treatment Follow-up Period)." Subjects were allowed the use of permitted analgesic rescue therapy on an as needed basis. ● Update Selection of Study Population to split the combined Exclusion Criterion 6 into 2 separate criteria to clarify malignancy Criterion 6 and neuropsychiatric Criterion 7. ● Update Prohibited Therapy to remove prescription amphetamine, or amphetamine-like drugs, and to add cannabinoids inclusive of any marijuana use, as prohibited medications. ● Update Permitted Rescue Therapy to remove Tramadol 50 mg. ● Update Efficacy, Pharmacokinetic, Pharmacodynamic and Safety Assessments as follows: - Efficacy and Safety Measurements Assessed to provide clarifications and incorporate applicable changes within the body text of the protocol. - Increase the visit window from 4 to 5 days. - Update Medical/Social History to add a collection of documentation of drug abuse (licit or illicit) at Day 1. - Update Pap Test to add biopsy with colposcopy, and to clarify that both colposcopy and biopsy results should be discussed with the sponsor. - Update Study Procedures with a footnote to clarify 8-hour minimum fast for Clinical/Safety Laboratory Tests. - Update Clinical Laboratory Tests, to change "Any repeat testing must be approved" to "Any repeat testing should be approved by an AbbVie representative." - Update BMD to allow scans be performed within 5 days of scheduled visit ● Update Adverse Event Reporting to include a 24-hour hotline for the investigator to contact AbbVie on-call physician in emergency. ● Update Pregnancy to add "any" to clarify that outcome of any pregnancy should be collected ● Update Statistical Methods to clarify methods.
    24 Sep 2015
    The purpose of this amendment was to: ● Remove fasting requirement on study drug administration ● Add requirement on use of calcium and vitamin D daily during the PTFU Period. ● Clarify that a brief physical examination is conducted only if there are reported symptoms. ● Instruct on use of the same modality consistently to measure body temperature. ● Clarify that subjects with a Pap diagnosis of atypical squamous cells of undetermined significance (ASC-US) with high risk human papillomavirus (HPV) or low-grade squamous intraepithelial lesion (LSIL) should undergo additional evaluation with colposcopy and biopsy, if applicable per local guidelines. ● Clarify that pregnancy testing applies to all subjects, whether exempted from use of a dual barrier non-hormonal contraception or not, and request that subjects attest on use of allowable contraception methods at every visit. ● Add requirement for DXA Scan at Month 6 in the PTFU Period for all subjects. ● Change the capacity of the collection tubes and the amount of serum collected from 4 mL to 3 mL. ● Add change from baseline in ECG to the safety variables. ● Clarify that temperature must be recorded each business day to document proper temperature of clinical supplies. ● Clarify that changes in BMD may be considered an AE if resulting in discontinuation from the study. ● Instruct sites to complete an SAE on the non-CRF forms and provide guidance when access to RAVE® is unavailable. ● Add specifics on time windows for analyses, referencing the SAP. ● Replace "nominal day" with "reference study day," and clarify window calculation for Month 1. ● Clarify that sensitivity analyses are done for the proportion of DYS and NMPP responders at Month 6. ● Remove the statement on "Subjects who discontinue for other reasons will be categorized according to LOCF." ● Add that information on responders will be based on the ROC thresholds calculated in Study M12-671. ● Specify which variable will be analyzed at EOT.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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