Efficacy and Safety Study of Elagolix in Women With Endometriosis

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00973973
• Collaborator: (none)
• Enrollment: 137
• Arms: 2
• Actual Duration (Months): 11.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate elagolix (NBI-56418) compared to placebo for its effects on endometriosis related pelvic pain and its safety.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis, Pain	Drug: Placebo; Drug: Elagolix	Phase 2

Detailed Description

Participants were randomized (1:1) to 150 mg elagolix once daily or placebo once daily for the first 8 weeks of the study. Following 8 weeks of dosing, participants continued in the study for an additional 16 weeks in an open-label phase where all participants still enrolled in the study received 150 mg elagolix once daily.

There was no pre-specified primary efficacy end point for this study as there is no single key efficacy outcome measure in this exploratory Phase 2 study. However, the efficacy measures of primary interest included the daily assessment of dysmenorrhea, non-menstrual pelvic pain and dyspareunia on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) using an e-Diary.

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NBI-56418 Sodium in Subjects With Endometriosis
• Actual Study Start Date: Oct 12, 2009
• Actual Primary Completion Date: Sep 22, 2010
• Actual Study Completion Date: Sep 22, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elagolix 150 mg Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.	Drug: Elagolix; Immediate release (IR) tablets taken orally once a day; Other Names: NBI-56418 Orilissa™
Placebo Comparator: Placebo Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Drug: Placebo; Matching placebo tablets taken orally once a day; Drug: Elagolix; Immediate release (IR) tablets taken orally once a day; Other Names: NBI-56418 Orilissa™

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Monthly Mean Dysmenorrhea Score During the Double-blind Treatment Phase [Baseline and Weeks 4 and 8]

   Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an electronic diary (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. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit.

2. Change From Baseline in the Monthly Mean Dysmenorrhea Score During the Open-label and Posttreatment Phases [Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

   Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an electronic diary (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. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.

3. Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score During the Double-Blind Treatment Phase [Baseline and weeks 4 and 8]

   Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having 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. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit.

4. Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score During the Open-label and Posttreatment Phases [Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

   Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having 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. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.

5. Change From Baseline in the Monthly Mean Cumulative Pain Score During the Double-Blind Treatment Phase [Baseline and weeks 4 and 8]

   Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time each day in an e-Diary 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. The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) reported during the 4 weeks prior to each visit.

6. Change From Baseline in the Monthly Mean Cumulative Pain Score During the Open-label and Posttreatment Phases [Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

   Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time each day in an e-Diary according to the following: 0: No discomfort 1: Mild discomfort, I was easily able to do the things I usually do 2: Moderate discomfort or pain making it difficult to do some of the things I usually do 3: Severe pain making it difficult to do the things I usually do The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.

7. Change From Baseline in the Monthly Mean Dyspareunia Score During the Double-Blind Treatment Phase [Baseline and weeks 4 and 8]

   Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: 0 = Absent; No discomfort during sexual intercourse 1 = Mild; I was able to tolerate the discomfort during sexual intercourse 2 = Moderate; Intercourse was interrupted due to pain 3 = Severe; I avoided intercourse because of pain Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each visit. Responses of "does not apply" were not included in the calculations.

8. Change From Baseline in the Monthly Mean Dyspareunia Score During the Open-label and Posttreatment Phases [Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

   Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: 0: Absent; No discomfort during sexual intercourse 1: Mild; I was able to tolerate the discomfort during sexual intercourse 2: Moderate; Intercourse was interrupted due to pain 3: Severe; I avoided intercourse because of pain Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each visit, except for week 30 which is based on 6 weeks of data. Responses of "does not apply" were not included in the calculations.

Secondary Outcome Measures

1. Percentage of Participants With a Response in Monthly Mean Dysmenorrhea Score at Week 8 [Baseline and Week 8]

   Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time 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. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each time point. Response was defined as the percentage of participants with a percent decrease from baseline in the week 8 monthly mean score that was greater than or equal to each specified threshold value (10% through 90% in steps of 10%).

2. Percentage of Participants With a Response in Monthly Mean Non-menstrual Pelvic Pain Score at Week 8 [Baseline and Week 8]

   Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having 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. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each time point. Response is defined as the percentage of participants with a percent decrease from baseline in the week 8 monthly mean score that was greater than or equal to each specified threshold value (10% through 90% in steps of 10%).

3. Percentage of Participants With a Response in Monthly Mean Cumulative Pain Score at Week 8 [Baseline and Week 8]

   Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time every day in an e-Diary according to the following: 0 = No discomfort 1 = Mild discomfort 2 = Moderate discomfort or pain 3 = Severe pain The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) in the 4 weeks prior to each time point. Response is the percentage of participants with a percent decrease from baseline in the week 8 monthly mean score that was greater than or equal to each specified threshold value (10% through 90% in steps of 10%).

4. Percentage of Participants With a Response in Monthly Mean Dyspareunia Score at Week 8 [Baseline and Week 8]

   Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: 0 = Absent; No discomfort during sexual intercourse 1 = Mild; I was able to tolerate the discomfort during sexual intercourse 2 = Moderate; Intercourse was interrupted due to pain 3 = Severe; I avoided intercourse because of pain Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each time point. Response is defined as the percentage of participants with a percent decrease from baseline in the week 8 monthly mean score that was greater than or equal to each specified threshold value (10% through 90% in steps of 10%).

5. Change From Baseline in the Percentage of Days of Any Analgesic Use During the Double-Blind Treatment Phase [Baseline and Weeks 4 and 8]

   The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of any analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of an analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").

6. Change From Baseline in the Percentage of Days of Any Analgesic Use During the Open-Label and Posttreatment Phases [Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

   The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of any analgesic use is defined as the number of days in the 4 weeks prior to each study visit (except for week 30 which is based on 6 weeks of data) that the participant reported the use of an analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").

7. Change From Baseline in the Percentage of Days of Prescription Analgesic Use During the Double-Blind Treatment Phase [Baseline and Weeks 4 and 8]

   The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of prescription analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of a prescription analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").

8. Change From Baseline in the Percentage of Days of Prescription Analgesic Use During the Open-Label and Posttreatment Phases [Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

   The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of prescription analgesic use is defined as the number of days in the 4 weeks prior to each study visit (except for week 30 which is based on 6 weeks of data) that the participant reported the use of a prescription analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").

9. Change From Baseline in the Percentage of Days of Narcotic Analgesic Use During the Double-Blind Treatment Phase [Baseline and Weeks 4 and 8]

   The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of narcotic analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of a narcotic analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").

10. Change From Baseline in the Percentage of Days of Narcotic Analgesic Use During the Open-Label and Posttreatment Phases [Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

    The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of narcotic analgesic use is defined as the number of days in the 4 weeks prior to each study visit (except for week 30 which is based on 6 weeks of data) that the participant reported the use of a narcotic analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").

11. Change From Baseline to the End of the Double-blind Treatment Phase in Composite Pelvic Signs and Symptoms Score (CPSSS) Total Score and Component Scores [Baseline and Week 8]

    The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Dysmenorrhea, dyspareunia, and non-menstrual pelvic pain scores are based on the participant's assessment of symptoms during the past 28 days; pelvic tenderness and induration were assessed by the investigator based on findings associated with a pelvic examination. The total CPSSS has a maximum possible value of 15 (total score range: 0 to 15, where a lower score indicates less signs and symptoms of endometriosis or better functioning). Individual component scores range from 0 (absent) to 3 (severe).

12. Change From Baseline to the End of the Open-label Treatment Phase in Composite Pelvic Signs and Symptoms Score (CPSSS) Total Score and Component Scores [Baseline and week 24]

    The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Dysmenorrhea, dyspareunia, and non-menstrual pelvic pain scores are based on the participant's assessment of symptoms during the past 28 days; pelvic tenderness and induration were assessed by the investigator based on findings associated with a pelvic examination. The total CPSSS has a maximum possible value of 15 (total score range: 0 to 15, where a lower score indicates less signs and symptoms of endometriosis or better functioning). Individual component scores range from 0 (absent) to 3 (severe).

13. Patient Global Impression of Change During the Double-blind Treatment Phase [Weeks 4 and 8]

    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: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse

14. Patient Global Impression of Change During the Open-Label and Posttreatment Phases [Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

    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: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse

15. Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved During the Double-blind Treatment Phase [Weeks 4 and 8]

    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: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse

16. Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved During the Open-label Treatment Phase [Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)]

    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: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse

17. Change From Baseline to the End of the Double-blind Treatment Phase in Endometriosis Health Profile-5 (EHP-5) [Baseline and week 8]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the impact of endometriosis in areas of pain, control and powerlessness, emotional well-being, social support, and self-image with five response categories for each item (Never, Rarely, Sometimes, Often, Always) A supplemental questionnaire consisting of six additional questions which assess the impact of endometriosis on the areas of work, relationship with children, sexual intercourse, feelings about the medical profession, treatment, and infertility with the same five response categories plus an additional response category of Not Relevant which was not scored. The scores associated with each possible outcome category are as follows: never (0), rarely (25), sometimes (50), often (75), and always (100). A negative change from baseline score indicates improvement in quality of life.

18. Change From Baseline to the End of the Open-label Treatment Phase in Endometriosis Health Profile-5 (EHP-5) [Baseline and week 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the impact of endometriosis on areas of pain, control and powerlessness, emotional well-being, social support, and self-image with five response categories for each item (Never, Rarely, Sometimes, Often, Always) A supplemental questionnaire consisting of six additional questions which assess the impact of endometriosis on areas of work, relationship with children, sexual intercourse, feelings about the medical profession, treatment, and infertility with the same five response categories plus an additional response category of Not Relevant which was not scored. The scores associated with each possible outcome category are as follows: never (0), rarely (25), sometimes (50), often (75), and always (100). A negative change from baseline score indicates improvement in quality of life.

19. Percentage of Days With Uterine Bleeding During the Double- Blind Treatment Phase [Screening (8 weeks prior to day 1) and the double-blind treatment phase (Weeks 1-8)]

    Uterine bleeding was reported daily by participants during the study using the e-Diary. The percentage of days a participant reported any bleeding was calculated as the total number of days the participant reported any bleeding ( light, moderate, or heavy) divided by the total number of days the participant had a non-missing e-Diary report of vaginal bleeding in the phase.

20. Number of Days to First Posttreatment Menses [From last day of study drug up to 6 weeks after the last dose.]

    Defined as the number of days from the last dose of study drug until the start date of the first post-treatment menses.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Be female, aged 18 to 49 years, inclusive.

• Have moderate to severe pelvic pain due to endometriosis.

• Have a history of regular menstrual cycles.

• Have been surgically (laparoscopy or laparotomy) diagnosed with endometriosis within 8 years of the start of screening.

• Have a Body Mass Index (BMI) of 18 to 36 kg/m², inclusive.

• Agree to use two forms of non-hormonal contraception during the study.

Exclusion Criteria:

• Are currently receiving gonadotropin-releasing hormone (GnRH) agonist, a GnRH antagonist other than NBI-56418, or danazol or have received any of these agents within 6 months of the start of screening.

• Are currently receiving subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular medroxyprogesterone acetate (DMPA-IM) or have received any of these agents within 3 months of the start of screening.

• Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within the last month.

• Have had surgery for endometriosis within the last month.

• Have had a hysterectomy or bilateral oophorectomy.

• Are using systemic steroids on a chronic or regular basis within 3 months.

• Have uterine fibroids ≥ 3 cm in diameter.

• Have pelvic pain that is not caused by endometriosis.

• Have unstable medical condition or chronic disease.

• Have been pregnant within the last six months.

• Currently breast feeding.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT00973973
• Other Study ID Numbers: NBI-56418-0901
• First Posted: Sep 9, 2009
• Last Update Posted: Sep 26, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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: Pelvic Pain,NBI-56418,Endometriosis
• Additional relevant MeSH terms: Endometriosis

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 37 centers in the United States.
Pre-assignment Detail	The study consisted of up to 8 weeks of screening with data collection to establish baseline pain, an 8-week double-blind placebo-controlled treatment period, a 16-week open-label treatment period with all patients receiving elagolix 150 mg once per day, and a 6-week posttreatment follow-up period.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Period Title: Double-blind Treatment Phase (Weeks 1-8)
STARTED	69	68
Received Study Drug	69	68
COMPLETED	63	60
NOT COMPLETED	6	8
Period Title: Double-blind Treatment Phase (Weeks 1-8)
STARTED	63	60
COMPLETED	57	55
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Placebo	Elagolix 150 mg	Total
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.	Total of all reporting groups
Overall Participants	69	68	137
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.0 (0.9)	32.8 (0.7)	32.9 (0.6)
Sex: Female, Male (Count of Participants)
Female	69 100%	68 100%	137 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	2 2.9%	2 1.5%
Asian	0 0%	0 0%	0 0%
Black	7 10.1%	6 8.8%	13 9.5%
White	57 82.6%	55 80.9%	112 81.8%
Hispanic	5 7.2%	5 7.4%	10 7.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Monthly Mean Dysmenorrhea Score During the Double-blind Treatment Phase
Description	Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an electronic diary (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. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Week 4	-0.24 (0.076)	-0.49 (0.076)
Week 8	-0.37 (0.107)	-1.13 (0.107)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of Change from Baseline at Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0262
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA) model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.45 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.107
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA) model, including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.06 to -0.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.152
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in the Monthly Mean Dysmenorrhea Score During the Open-label and Posttreatment Phases
Description	Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an electronic diary (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. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.
Time Frame	Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Week 12	-0.768 (0.118)	-1.060 (0.130)
Week 16	-1.325 (0.112)	-1.022 (0.137)
Week 20	-1.026 (0.119)	-0.991 (0.121)
Week 24	-1.282 (0.118)	-1.372 (0.132)
Week 30	-0.547 (0.104)	-0.534 (0.102)

3. Primary Outcome

Title	Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score During the Double-Blind Treatment Phase
Description	Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having 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. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Week 4	-0.05 (0.061)	-0.26 (0.061)
Week 8	-0.19 (0.071)	-0.47 (0.071)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0163
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.38 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.086
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0066
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.48 to -0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.101
	Estimation Comments

4. Primary Outcome

Title	Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score During the Open-label and Posttreatment Phases
Description	Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having 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. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.
Time Frame	Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Week 12	-0.355 (0.087)	-0.727 (0.072)
Week 16	-0.422 (0.078)	-0.763 (0.079)
Week 20	-0.524 (0.090)	-0.759 (0.082)
Week 24	-0.543 (0.092)	-0.801 (0.082)
Week 30	-0.326 (0.104)	-0.689 (0.085)

5. Primary Outcome

Title	Change From Baseline in the Monthly Mean Cumulative Pain Score During the Double-Blind Treatment Phase
Description	Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time each day in an e-Diary 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. The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) reported during the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Week 4	-0.11 (0.058)	-0.32 (0.058)
Week 8	-0.21 (0.070)	-0.55 (0.070)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0089
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.38 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.082
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.53 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.100
	Estimation Comments

6. Primary Outcome

Title	Change From Baseline in the Monthly Mean Cumulative Pain Score During the Open-label and Posttreatment Phases
Description	Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time each day in an e-Diary according to the following: 0: No discomfort 1: Mild discomfort, I was easily able to do the things I usually do 2: Moderate discomfort or pain making it difficult to do some of the things I usually do 3: Severe pain making it difficult to do the things I usually do The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.
Time Frame	Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Week 12	-0.433 (0.082)	-0.781 (0.070)
Week 16	-0.530 (0.072)	-0.793 (0.083)
Week 20	-0.615 (0.085)	-0.798 (0.081)
Week 24	-0.655 (0.088)	-0.878 (0.082)
Week 30	-0.374 (0.095)	-0.666 (0.085)

7. Primary Outcome

Title	Change From Baseline in the Monthly Mean Dyspareunia Score During the Double-Blind Treatment Phase
Description	Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: 0 = Absent; No discomfort during sexual intercourse 1 = Mild; I was able to tolerate the discomfort during sexual intercourse 2 = Moderate; Intercourse was interrupted due to pain 3 = Severe; I avoided intercourse because of pain Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each visit. Responses of "does not apply" were not included in the calculations.
Time Frame	Baseline and weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with non-missing data at each time point. If a participant's responses were all "does not apply" for that month the score was treated as missing.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	59	53
Week 4	-0.07 (0.087)	-0.34 (0.091)
Week 8	-0.23 (0.095)	-0.61 (0.098)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change form baseline at week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0360
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.52 to -0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.127
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0070
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.137
	Estimation Comments

8. Primary Outcome

Title	Change From Baseline in the Monthly Mean Dyspareunia Score During the Open-label and Posttreatment Phases
Description	Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: 0: Absent; No discomfort during sexual intercourse 1: Mild; I was able to tolerate the discomfort during sexual intercourse 2: Moderate; Intercourse was interrupted due to pain 3: Severe; I avoided intercourse because of pain Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each visit, except for week 30 which is based on 6 weeks of data. Responses of "does not apply" were not included in the calculations.
Time Frame	Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12 and non-missing data at each time point. If a participant's responses were all "does not apply" for that month the score was treated as missing.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	53	47
Week 12	-0.334 (0.125)	-0.696 (0.112)
Week 16	-0.453 (0.114)	-0.738 (0.124)
Week 20	-0.492 (0.135)	-0.778 (0.121)
Week 24	-0.633 (0.155)	-0.789 (0.115)
Week 30	-0.300 (0.118)	-0.730 (0.118)

9. Secondary Outcome

Title	Percentage of Participants With a Response in Monthly Mean Dysmenorrhea Score at Week 8
Description	Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time 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. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each time point. Response was defined as the percentage of participants with a percent decrease from baseline in the week 8 monthly mean score that was greater than or equal to each specified threshold value (10% through 90% in steps of 10%).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with non-missing data at baseline and week 8.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	64	64
10% Reduction	56.3 81.6%	68.8 101.2%
20% Reduction	43.8 63.5%	68.8 101.2%
30% Reduction	32.8 47.5%	62.5 91.9%
40% Reduction	25.0 36.2%	59.4 87.4%
50% Reduction	15.6 22.6%	54.7 80.4%
60% Reduction	9.4 13.6%	51.6 75.9%
70% Reduction	4.7 6.8%	46.9 69%
80% Reduction	3.1 4.5%	43.8 64.4%
90% Reduction	3.1 4.5%	43.8 64.4%

10. Secondary Outcome

Title	Percentage of Participants With a Response in Monthly Mean Non-menstrual Pelvic Pain Score at Week 8
Description	Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having 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. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each time point. Response is defined as the percentage of participants with a percent decrease from baseline in the week 8 monthly mean score that was greater than or equal to each specified threshold value (10% through 90% in steps of 10%).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with non-missing data at baseline and week 8.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	64	64
10% Reduction	51.6 74.8%	79.7 117.2%
20% Reduction	40.6 58.8%	68.8 101.2%
30% Reduction	32.8 47.5%	62.5 91.9%
40% Reduction	25.0 36.2%	51.6 75.9%
50% Reduction	25.0 36.2%	32.8 48.2%
60% Reduction	20.3 29.4%	26.6 39.1%
70% Reduction	14.1 20.4%	21.9 32.2%
80% Reduction	9.4 13.6%	10.9 16%
90% Reduction	4.7 6.8%	7.8 11.5%

11. Secondary Outcome

Title	Percentage of Participants With a Response in Monthly Mean Cumulative Pain Score at Week 8
Description	Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time every day in an e-Diary according to the following: 0 = No discomfort 1 = Mild discomfort 2 = Moderate discomfort or pain 3 = Severe pain The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) in the 4 weeks prior to each time point. Response is the percentage of participants with a percent decrease from baseline in the week 8 monthly mean score that was greater than or equal to each specified threshold value (10% through 90% in steps of 10%).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with non-missing data at baseline and week 8.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	64	64
10% Reduction	51.6 74.8%	76.6 112.6%
20% Reduction	40.6 58.8%	70.3 103.4%
30% Reduction	37.5 54.3%	59.4 87.4%
40% Reduction	23.4 33.9%	46.9 69%
50% Reduction	20.3 29.4%	37.5 55.1%
60% Reduction	15.6 22.6%	26.6 39.1%
70% Reduction	7.8 11.3%	18.8 27.6%
80% Reduction	3.1 4.5%	9.4 13.8%
90% Reduction	0.0 0%	9.4 13.8%

12. Secondary Outcome

Title	Percentage of Participants With a Response in Monthly Mean Dyspareunia Score at Week 8
Description	Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: 0 = Absent; No discomfort during sexual intercourse 1 = Mild; I was able to tolerate the discomfort during sexual intercourse 2 = Moderate; Intercourse was interrupted due to pain 3 = Severe; I avoided intercourse because of pain Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each time point. Response is defined as the percentage of participants with a percent decrease from baseline in the week 8 monthly mean score that was greater than or equal to each specified threshold value (10% through 90% in steps of 10%).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with non-missing data at baseline and week 8. If a participant's responses were all "does not apply" for that month the score was treated as missing.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	47	45
10% Reduction	44.7 64.8%	73.3 107.8%
20% Reduction	38.3 55.5%	64.4 94.7%
30% Reduction	34.0 49.3%	57.8 85%
40% Reduction	27.7 40.1%	53.3 78.4%
50% Reduction	23.4 33.9%	48.9 71.9%
60% Reduction	19.1 27.7%	37.8 55.6%
70% Reduction	19.1 27.7%	31.1 45.7%
80% Reduction	17.0 24.6%	22.2 32.6%
90% Reduction	12.8 18.6%	20.0 29.4%

13. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Any Analgesic Use During the Double-Blind Treatment Phase
Description	The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of any analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of an analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Time Frame	Baseline and Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Week 4	-5.78 (2.782)	-15.62 (2.782)
Week 8	-9.19 (2.763)	-21.63 (2.763)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0137
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.84
	Confidence Interval	(2-Sided) 95%; -17.63 to -2.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.939
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-12.44
	Confidence Interval	(2-Sided) 95%; -20.19 to -4.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.913
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Any Analgesic Use During the Open-Label and Posttreatment Phases
Description	The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of any analgesic use is defined as the number of days in the 4 weeks prior to each study visit (except for week 30 which is based on 6 weeks of data) that the participant reported the use of an analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Time Frame	Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Week 12	-14.91 (3.76)	-27.70 (3.49)
Week 16	-18.34 (3.33)	-26.27 (3.71)
Week 20	-19.82 (4.05)	-26.35 (4.27)
Week 24	-20.63 (4.17)	-29.21 (4.23)
Week 30	-11.64 (4.18)	-21.83 (4.30)

15. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Prescription Analgesic Use During the Double-Blind Treatment Phase
Description	The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of prescription analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of a prescription analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Time Frame	Baseline and Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Week 4	0.92 (1.929)	-5.29 (1.929)
Week 8	-0.82 (1.802)	-7.16 (1.802)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0244
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.21
	Confidence Interval	(2-Sided) 95%; -11.61 to -0.81
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.728
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0141
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.35
	Confidence Interval	(2-Sided) 95%; -11.39 to -1.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.549
	Estimation Comments

16. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Prescription Analgesic Use During the Open-Label and Posttreatment Phases
Description	The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of prescription analgesic use is defined as the number of days in the 4 weeks prior to each study visit (except for week 30 which is based on 6 weeks of data) that the participant reported the use of a prescription analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Time Frame	Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Week 12	-2.34 (2.70)	-8.53 (1.66)
Week 16	-5.52 (2.26)	-7.52 (1.67)
Week 20	-5.21 (2.78)	-6.06 (2.31)
Week 24	-5.89 (2.56)	-7.83 (1.89)
Week 30	-0.72 (3.07)	-6.06 (2.26)

17. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Narcotic Analgesic Use During the Double-Blind Treatment Phase
Description	The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of narcotic analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of a narcotic analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Time Frame	Baseline and Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Week 4	-0.51 (1.287)	-3.63 (1.287)
Week 8	-1.19 (1.369)	-4.71 (1.369)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0893
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.12
	Confidence Interval	(2-Sided) 95%; -6.72 to 0.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.821
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0720
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.52
	Confidence Interval	(2-Sided) 95%; -7.35 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.938
	Estimation Comments

18. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Narcotic Analgesic Use During the Open-Label and Posttreatment Phases
Description	The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of narcotic analgesic use is defined as the number of days in the 4 weeks prior to each study visit (except for week 30 which is based on 6 weeks of data) that the participant reported the use of a narcotic analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Time Frame	Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Week 12	-1.91 (2.16)	-4.79 (1.25)
Week 16	-4.03 (1.76)	-3.64 (1.27)
Week 20	-2.79 (2.24)	-5.41 (1.64)
Week 24	-3.12 (2.20)	-3.92 (1.68)
Week 30	0.75 (2.73)	-3.56 (1.69)

19. Secondary Outcome

Title	Change From Baseline to the End of the Double-blind Treatment Phase in Composite Pelvic Signs and Symptoms Score (CPSSS) Total Score and Component Scores
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Dysmenorrhea, dyspareunia, and non-menstrual pelvic pain scores are based on the participant's assessment of symptoms during the past 28 days; pelvic tenderness and induration were assessed by the investigator based on findings associated with a pelvic examination. The total CPSSS has a maximum possible value of 15 (total score range: 0 to 15, where a lower score indicates less signs and symptoms of endometriosis or better functioning). Individual component scores range from 0 (absent) to 3 (severe).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at baseline and week 8.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Total Score	-2.19 (0.359)	-4.45 (0.356)
Dysmenorrhea Component	-0.39 (0.127)	-1.44 (0.127)
Non-menstrual Pelvic Pain Component	-0.54 (0.101)	-0.90 (0.101)
Dyspareunia Component	-0.46 (0.123)	-0.74 (0.121)
Pelvic Tenderness Component	-0.41 (0.102)	-0.80 (0.101)
Pelvic Induration Component	-0.38 (0.089)	-0.66 (0.088)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of the change from baseline in CPSSS total score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.26
	Confidence Interval	(2-Sided) 95%; -3.26 to -1.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.505
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline in CPSSS component of dysmenorrhea score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.05
	Confidence Interval	(2-Sided) 95%; -1.41 to -0.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.180
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline in CPSSS component of non-menstrual pelvic pain score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0139
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.64 to -0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.143
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline in CPSSS component of dyspareunia score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1052
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.63 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.173
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline in CPSSS component of pelvic tenderness score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0081
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.67 to -0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.143
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of change from baseline in CPSSS component of induration score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0240
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including baseline value as a covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.53 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.125
	Estimation Comments

20. Secondary Outcome

Title	Change From Baseline to the End of the Open-label Treatment Phase in Composite Pelvic Signs and Symptoms Score (CPSSS) Total Score and Component Scores
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Dysmenorrhea, dyspareunia, and non-menstrual pelvic pain scores are based on the participant's assessment of symptoms during the past 28 days; pelvic tenderness and induration were assessed by the investigator based on findings associated with a pelvic examination. The total CPSSS has a maximum possible value of 15 (total score range: 0 to 15, where a lower score indicates less signs and symptoms of endometriosis or better functioning). Individual component scores range from 0 (absent) to 3 (severe).
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 24. The analysis includes participants with non-missing data for each component at baseline and week 24.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	57	57
Total Score	-5.571 (0.451)	-5.404 (0.384)
Dysmenorrhea Component	-1.544 (0.175)	-1.386 (0.175)
Non-menstrual Pelvic Pain Component	-1.000 (0.128)	-1.211 (0.127)
Dyspareunia Component	-1.12 (0.17)	-0.77 (0.16)
Pelvic Tenderness Component	-1.000 (0.120)	-1.175 (0.112)
Pelvic Induration Component	-0.964 (0.142)	-0.807 (0.121)

21. Secondary Outcome

Title	Patient Global Impression of Change During the Double-blind Treatment Phase
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: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse
Time Frame	Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Week 4	3.6 (0.16)	2.8 (0.16)
Week 8	3.4 (0.18)	2.4 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of Patient Global Impression of Change at week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.23
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of Patient Global Impression of Change at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.5 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

22. Secondary Outcome

Title	Patient Global Impression of Change During the Open-Label and Posttreatment Phases
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: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse
Time Frame	Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Week 12	2.5 (0.2)	2.0 (0.1)
Week 16	2.4 (0.2)	1.8 (0.1)
Week 20	2.2 (0.2)	2.0 (0.1)
Week 24	2.0 (0.2)	1.8 (0.1)
Week 30	2.4 (0.2)	2.2 (0.2)

23. Secondary Outcome

Title	Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved During the Double-blind Treatment Phase
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: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse
Time Frame	Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	66	66
Week 4	18.5 26.8%	37.9 55.7%
Week 8	30.2 43.8%	60.3 88.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of response rates at week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0136
	Comments
	Method	Pearson chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	19.4
	Confidence Interval	(2-Sided) 95%; 4.4 to 34.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Comparison of response rates at week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Pearson chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	30.2
	Confidence Interval	(2-Sided) 95%; 13.6 to 46.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved During the Open-label Treatment Phase
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: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse
Time Frame	Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Week 12	59.0 85.5%	76.3 112.2%
Week 16	61.7 89.4%	76.3 112.2%
Week 20	71.9 104.2%	71.9 105.7%
Week 24	73.7 106.8%	86.0 126.5%
Week 30	69.1 100.1%	73.6 108.2%

25. Secondary Outcome

Title	Change From Baseline to the End of the Double-blind Treatment Phase in Endometriosis Health Profile-5 (EHP-5)
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the impact of endometriosis in areas of pain, control and powerlessness, emotional well-being, social support, and self-image with five response categories for each item (Never, Rarely, Sometimes, Often, Always) A supplemental questionnaire consisting of six additional questions which assess the impact of endometriosis on the areas of work, relationship with children, sexual intercourse, feelings about the medical profession, treatment, and infertility with the same five response categories plus an additional response category of Not Relevant which was not scored. The scores associated with each possible outcome category are as follows: never (0), rarely (25), sometimes (50), often (75), and always (100). A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population). The analysis includes participants with non-missing data at baseline and week 8 for each question.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	63	63
Pain	-12.3 (3.2)	-29.0 (3.0)
Control and Powerlessness	-12.7 (3.2)	-35.3 (3.7)
Emotional Well-being	-10.3 (2.9)	-17.1 (3.1)
Social Support	-13.1 (3.5)	-27.8 (3.9)
Self-image	-7.1 (3.3)	-23.4 (3.5)
Work	-13.0 (3.4)	-26.4 (3.4)
Relationship with Children	-19.0 (4.8)	-31.5 (5.5)
Sexual Intercourse	-14.3 (2.9)	-22.6 (3.8)
Medical Profession	-9.5 (2.9)	-11.5 (3.3)
Frustration with Treatment	-20.8 (5.1)	-36.5 (4.6)
Concerns with Infertility	-10.6 (3.6)	-14.1 (3.3)

26. Secondary Outcome

Title	Change From Baseline to the End of the Open-label Treatment Phase in Endometriosis Health Profile-5 (EHP-5)
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the impact of endometriosis on areas of pain, control and powerlessness, emotional well-being, social support, and self-image with five response categories for each item (Never, Rarely, Sometimes, Often, Always) A supplemental questionnaire consisting of six additional questions which assess the impact of endometriosis on areas of work, relationship with children, sexual intercourse, feelings about the medical profession, treatment, and infertility with the same five response categories plus an additional response category of Not Relevant which was not scored. The scores associated with each possible outcome category are as follows: never (0), rarely (25), sometimes (50), often (75), and always (100). A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 10 evaluable e-Diary reports during the double-blind period (intent-to-treat population) with data on or after Week 12. The analysis includes participants with non-missing data at baseline and week 24 for each question.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	61	60
Pain	-30.3 (3.9)	-36.4 (2.9)
Control and Powerlessness	-35.1 (4.3)	-39.5 (3.5)
Emotional Well-being	-22.8 (4.0)	-23.7 (3.3)
Social Support	-29.8 (4.5)	-37.7 (4.1)
Self-image	-20.6 (4.3)	-25.9 (3.9)
Work	-27.6 (4.4)	-37.0 (3.1)
Relationship with Children	-39.6 (5.4)	-40.0 (4.2)
Sexual Intercourse	-30.1 (3.9)	-27.2 (4.0)
Medical Profession	-16.8 (4.5)	-19.6 (3.9)
Frustration with Treatment	-40.1 (5.5)	-40.6 (4.4)
Concerns with Infertility	-20.8 (5.0)	-22.8 (3.8)

27. Secondary Outcome

Title	Percentage of Days With Uterine Bleeding During the Double- Blind Treatment Phase
Description	Uterine bleeding was reported daily by participants during the study using the e-Diary. The percentage of days a participant reported any bleeding was calculated as the total number of days the participant reported any bleeding ( light, moderate, or heavy) divided by the total number of days the participant had a non-missing e-Diary report of vaginal bleeding in the phase.
Time Frame	Screening (8 weeks prior to day 1) and the double-blind treatment phase (Weeks 1-8)

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) with non-missing data.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	69	68
Screening	24.29 (0.96)	22.98 (1.12)
Double-Blind Treatment Phase (Weeks 1-8)	23.91 (1.62)	14.00 (1.03)

28. Secondary Outcome

Title	Number of Days to First Posttreatment Menses
Description	Defined as the number of days from the last dose of study drug until the start date of the first post-treatment menses.
Time Frame	From last day of study drug up to 6 weeks after the last dose.

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) with non-missing post-treatment data.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.	Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Measure Participants	56	58
Median (Full Range) [days]	22.0	25.0

Adverse Events

Time Frame	From the first dose of any study drug through week 24. The Placebo treatment group includes data for the 8-week double-blind treatment phase. The Elagolix treatment group included data for the total 24-week treatment period for participants initially randomized to elagolix, and 16-week open-label treatment period for participants initially randomized to placebo.
Arm/Group Title	Placebo		Elagolix
Arm/Group Description	Participants received placebo orally once a day for 8 weeks during the double-blind treatment period.		Participants initially randomized to elagolix received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period. Participants originally randomized to placebo were switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.
All Cause Mortality
	Placebo		Elagolix
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/131 (0%)
Serious Adverse Events
	Placebo		Elagolix
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/69 (4.3%)		1/131 (0.8%)
Gastrointestinal disorders
ABDOMINAL PAIN LOWER	0/69 (0%)	0	1/131 (0.8%)	1
Nervous system disorders
CONVULSION	1/69 (1.4%)	1	0/131 (0%)	0
Pregnancy, puerperium and perinatal conditions
ABORTION SPONTANEOUS	1/69 (1.4%)	1	0/131 (0%)	0
Psychiatric disorders
DEPRESSION SUICIDAL	1/69 (1.4%)	1	0/131 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Elagolix
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/69 (18.8%)		49/131 (37.4%)
Gastrointestinal disorders
NAUSEA	3/69 (4.3%)	3	13/131 (9.9%)	13
Infections and infestations
NASOPHARYNGITIS	1/69 (1.4%)	1	7/131 (5.3%)	7
SINUSITIS	5/69 (7.2%)	5	8/131 (6.1%)	9
UPPER RESPIRATORY TRACT INFECTION	4/69 (5.8%)	4	8/131 (6.1%)	10
Nervous system disorders
HEADACHE	3/69 (4.3%)	3	13/131 (9.9%)	20
Vascular disorders
HOT FLUSH	1/69 (1.4%)	1	13/131 (9.9%)	13

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.