An Efficacy and Safety Study of Elagolix (NBI-56418) in Women With Endometriosis

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00619866
• Collaborator: (none)
• Enrollment: 155
• Arms: 3
• Actual Duration (Months): 18.3

Study Details

Study Description

Brief Summary

This study is designed to see how elagolix works compared to placebo in women with endometriosis and to see the effect, if any, on bone mineral density.

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

Detailed Description

This is a Phase II, multicenter, randomized, double-blind, placebo-controlled parallel-group study to assess the efficacy and safety of elagolix at two dose levels administered once daily for up to 6 months. Participants will be randomized (1:1:1) to one of the following treatment groups for the first 12 weeks of dosing: 150 mg elagolix once daily (QD); 250 mg elagolix QD or placebo QD. Following 12 weeks of dosing, participants will continue in the study for an additional 12 weeks; participants randomized to elagolix will continue to receive their assigned dose and participants randomized to placebo will be re-randomized to receive one of the two doses of elagolix for 12 weeks in a double-blind fashion. Six weeks after the last dose of study drug at the end of Week 24, a follow-up visit will be performed (end of Week 30).

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NBI-56418 in Subjects With Endometriosis
• Actual Study Start Date: Feb 19, 2008
• Actual Primary Completion Date: Apr 20, 2009
• Actual Study Completion Date: Aug 28, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Drug: placebo; Placebo tablet administered orally
Experimental: Elagolix 150 mg Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Drug: Elagolix; Elagolix tablets administered orally; Other Names: NBI-56418 Orilissa™
Experimental: Elagolix 250 mg Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.	Drug: Elagolix; Elagolix tablets administered orally; Other Names: NBI-56418 Orilissa™

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain at Week 12 [Baseline and week 12]

   The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.

Secondary Outcome Measures

1. Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain [Baseline and weeks 4 and 8]

   The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.

2. Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain [Baseline and Weeks 4, 8, and 12]

   The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit.

3. Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score [Baseline and weeks 4, 8, and 12]

   Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time every day in an e-Diary according to the following response options: 0 = No pelvic pain 1 = Mild pelvic pain; subject could not do some of the things she usually does 2 = Moderate pelvic pain; subject could not do many of the things she usually does 3 = Severe pelvic pain; subject could not do most or all of the things she usually does. 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 Dysmenorrhea Score [Baseline and Weeks 4, 8, and 12]

   Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day in an e-Diary according to the following response options: Subject is not having her period 0 = No pain related to period 1 = Mild pain related to period; subject could not do some of the things she usually does 2 = Moderate pain related to period; subject could not do many of the things she usually does 3 = Severe pain related to period; subject could not do most of or all of the things she usually does. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit.

5. Change From Baseline in the Monthly Mean Total of Dysmenorrhea and Non-menstrual Pelvic Pain Scores [Baseline and Weeks 4, 8, and 12]

   Participants assessed dysmenorrhea and pelvic pain not related to menses and their impact on daily activities at approximately the same time every day on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe) in an e-Diary. The sum of the dysmenorrhea and non-menstrual pelvic pain scores on each day were calculated to create a daily total score. On days the participant was not having her period, the dysmenorrhea score was not defined; hence, the total score was equal to the non-menstrual pelvic pain score (range 0 to 3). On days where the participant recorded menstruation the total score ranged from 0 to 6, where higher scores indicate more severe pain. The monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores is the average of the daily values reported during the 4 weeks prior to each visit.

6. Percentage of Days With No Pain Based on NRS [Baseline and weeks 4, 8 and 12]

   The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The percentage of days a participant reported a value of zero (or "no pain") for the NRS was calculated for the 4 weeks prior to each visit.

7. Percentage of Days With No Pain Based Based on Non-menstrual Pelvic Pain Daily Assessment [Baseline and weeks 4, 8 and 12]

   Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time every day in an e-Diary according to the following response options: 0 = No pelvic pain 1 = Mild pelvic pain; subject could not do some of the things she usually does 2 = Moderate pelvic pain; subject could not do many of the things she usually does 3 = Severe pelvic pain; subject could not do most or all of the things she usually does. The percentage of days a participant reported a value of zero ("no pain") for non-menstrual pelvic pain was calculated for the 4 weeks prior to each visit.

8. Percentage of Days With No Pain Based Based on Dysmenorrhea Daily Assessment [Baseline and weeks 4, 8 and 12]

   Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day in an e-Diary according to the following response options: Subject is not having her period 0 = No pain related to period 1 = Mild pain related to period; subject could not do some of the things she usually does 2 = Moderate pain related to period; subject could not do many of the things she usually does = Severe pain related to period; subject could not do most of or all of the things she usually does. The percentage of days a participant reported a value of zero ("no pain") for dysmenorrhea was calculated for the 4 weeks prior to each visit.

9. Percentage of Days With No Pain Based Based on Total Score of Non-menstrual Pelvic Pain and Dysmenorrhea Daily Assessment [Baseline and weeks 4, 8 and 12]

   Participants assessed dysmenorrhea and pelvic pain not related to menses and their impact on daily activities at approximately the same time every day in an e-Diary on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The sum of the dysmenorrhea and non-menstrual pelvic pain scores on each day were calculated to create a daily total score. On days the participant was not having her period, the dysmenorrhea score was not defined; hence, the total score was equal to the non-menstrual pelvic pain score (range 0 to 3). On days where the participant recorded menstruation the total score ranged from 0 to 6, where higher scores indicate more severe pain. The percentage of days a participant reported a value of zero ("no pain") for the non-menstrual pelvic pain and dysmenorrhea total score was calculated for the 4 weeks prior to each visit.

10. Change From Baseline in the Percentage of Days of Any Analgesic Use [Baseline and Weeks 4, 8, and 12]

    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").

11. Change From Baseline in the Percentage of Days of Prescription Analgesic Use [Baseline and Weeks 4, 8, and 12]

    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").

12. Change From Baseline in the Percentage of Days of Narcotic Analgesic Use [Baseline and Weeks 4, 8, and 12]

    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").

13. Percentage of Participants With 30% Decrease From Baseline in Monthly Mean NRS [Baseline and weeks 4, 8 and 12]

    The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.

14. Percentage of Participants With 30% Decrease From Baseline in Monthly Peak NRS [Baseline and weeks 4, 8 and 12]

    The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit.

15. Percentage of Participants With 50% Decrease From Baseline in Monthly Mean NRS [Baseline and weeks 4, 8 and 12]

    The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.

16. Percentage of Participants With 50% Decrease From Baseline in Monthly Peak NRS [Baseline and weeks 4, 8 and 12]

    The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit.

17. Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) [Baseline and Weeks 4, 8, and 12]

    The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess dyspareunia (painful intercourse) participants were asked to select the best description of pain during sexual intercourse over the past 28 days using the following response categories: 0 = Absent; No discomfort during sexual intercourse. 1 = Mild; I can tolerate the discomfort during sexual intercourse. 2 = Moderate; Intercourse is sometime interrupted due to pain. 3 = Severe; I prefer to avoid intercourse because of pain. Not applicable. I am not sexually active for reasons other than my endometriosis symptoms.

18. Patient Global Impression of Change at Weeks 4, 8 and 12 [Weeks 4, 8, and 12]

    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

19. Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved [Weeks 4, 8, and 12]

    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

20. Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved [Weeks 4, 8, and 12]

    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

21. Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 [Baseline and week 12]

    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 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 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.

22. Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12 [Baseline and week 12]

    Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA).

23. Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 [Baseline and Week 24]

    Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA).

24. Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12 [Baseline and week 12]

    Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA).

25. Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 [Baseline and Week 24]

    Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA).

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 been surgically (laparoscopy) diagnosed with endometriosis within the last 8 years and have recurrent or persistent endometriosis symptoms

• Have regular menstrual cycle

• 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 or GnRH antagonist 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: NCT00619866
• Other Study ID Numbers: NBI-56418-0702
• First Posted: Feb 21, 2008
• Last Update Posted: Sep 7, 2018
• Last Verified: Mar 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: bone mineral density; Pelvic Pain; estradiol; NBI-56418
• Additional relevant MeSH terms: Endometriosis

Study Results

Participant Flow

Recruitment Details	The study was conducted at 50 centers in the United States from February 2008 to August 2009.
Pre-assignment Detail	Patients were randomized equally to oral elagolix 150 mg or 250 mg once daily, or placebo for 12 weeks. Thereafter, patients originally randomized to placebo were re-randomized to one of the two elagolix doses and patients originally randomized to elagolix continued their assigned dose for an additional 12 weeks.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Placebo / Elagolix 150 mg	Placebo / Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day (QD) for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 150 mg for 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.
Period Title: Weeks 1 - 12
STARTED	52	51	52	0	0
COMPLETED	38	45	42	0	0
NOT COMPLETED	14	6	10	0	0
Period Title: Weeks 1 - 12
STARTED	0	45	42	18	20
COMPLETED	0	38	37	14	18
NOT COMPLETED	0	7	5	4	2

Baseline Characteristics

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Total
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.	Total of all reporting groups
Overall Participants	52	51	52	155
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.2 (1.0)	30.9 (1.0)	31.0 (1.0)	31.0 (0.5)
Sex: Female, Male (Count of Participants)
Female	52 100%	51 100%	52 100%	155 100%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	0 0%	2 3.8%	2 1.3%
Black	4 7.7%	4 7.8%	3 5.8%	11 7.1%
White	43 82.7%	42 82.4%	41 78.8%	126 81.3%
Hispanic	3 5.8%	4 7.8%	6 11.5%	13 8.4%
Other	2 3.8%	1 2%	0 0%	3 1.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain at Week 12
Description	The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	38	44	45
Least Squares Mean (Standard Error) [units on a scale]	-0.88 (0.18)	-1.19 (0.18)	-1.25 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Change from baseline in in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2311
	Comments
	Method	Repeated Measures Analysis of Covariance
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.81 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Change from baseline in in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1521
	Comments
	Method	Repeated Measures Analysis of Covariance
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.86 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments	Difference = Elagolix - Placebo

2. Secondary Outcome

Title	Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain
Description	The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS 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 one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-0.60 (0.17)	-0.90 (0.17)	-0.83 (0.17)
Week 8	-0.71 (0.18)	-1.23 (0.17)	-0.94 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 4. Change from baseline in in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2041
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.77 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 4. Change from baseline in in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3375
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.69 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 8. Change from baseline in in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0354
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -1.01 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 8. Change from baseline in in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3618
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.71 to 0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments	Difference = Elagolix - Placebo

3. Secondary Outcome

Title	Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain
Description	The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and Weeks 4, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-1.27 (0.32)	-1.39 (0.32)	-1.58 (0.32)
Week 8	-1.25 (0.34)	-1.94 (0.33)	-2.41 (0.33)
Week 12	-1.30 (0.36)	-2.45 (0.34)	-2.74 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 4. Change from baseline in in monthly peak values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7990
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -1.01 to 0.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.46
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 4. Change from baseline in in monthly peak values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5042
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -1.21 to 0.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.46
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 8. Change from baseline in in monthly peak values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1459
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 95%; -1.63 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.48
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 8. Change from baseline in in monthly peak values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0163
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -2.10 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.48
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 12. Change from baseline in in monthly peak values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0207
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.15
	Confidence Interval	(2-Sided) 95%; -2.13 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.50
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 12. Change from baseline in in monthly peak values of the NRS for overall endometriosis-associated pelvic pain was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.44
	Confidence Interval	(2-Sided) 95%; -2.42 to -0.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.50
	Estimation Comments	Difference = Elagolix - Placebo

4. Secondary Outcome

Title	Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score
Description	Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time every day in an e-Diary according to the following response options: 0 = No pelvic pain 1 = Mild pelvic pain; subject could not do some of the things she usually does 2 = Moderate pelvic pain; subject could not do many of the things she usually does 3 = Severe pelvic pain; subject could not do most or all of the things she usually does. 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, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-0.14 (0.05)	-0.18 (0.05)	-0.16 (0.05)
Week 8	-0.12 (0.05)	-0.30 (0.05)	-0.17 (0.05)
Week 12	-0.22 (0.06)	-0.27 (0.05)	-0.25 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 4. Change from baseline in non-menstrual pelvic pain score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5744
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 4. Change from baseline in non-menstrual pelvic pain score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7280
	Comments
	Method	Repeated measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 8. Change from baseline in non-menstrual pelvic pain score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0195
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95%; -0.32 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 8. Change from baseline in non-menstrual pelvic pain score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5589
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 12. Change from baseline in non-menstrual pelvic pain score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5558
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 12. Change from baseline in non-menstrual pelvic pain score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7121
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments	Difference = Elagolix - Placebo

5. Secondary Outcome

Title	Change From Baseline in the Monthly Mean Dysmenorrhea Score
Description	Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day in an e-Diary according to the following response options: Subject is not having her period 0 = No pain related to period 1 = Mild pain related to period; subject could not do some of the things she usually does 2 = Moderate pain related to period; subject could not do many of the things she usually does 3 = Severe pain related to period; subject could not do most of or all of the things she usually does. 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, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-0.20 (0.09)	-0.49 (0.09)	-0.40 (0.09)
Week 8	-0.29 (0.10)	-0.71 (0.09)	-0.79 (0.09)
Week 12	-0.24 (0.10)	-0.68 (0.10)	-0.76 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 4. Change from baseline in dysmenorrhea score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0286
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.54 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 4. Change from baseline in dysmenorrhea score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1210
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.45 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 8. Change from baseline in dysmenorrhea score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.68 to -0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 8. Change from baseline in dysmenorrhea score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.76 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 12. Change from baseline in dysmenorrhea score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95%; -0.72 to -0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 12. Change from baseline in dysmenorrhea score was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -0.80 to -0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments	Difference = Elagolix - Placebo

6. Secondary Outcome

Title	Change From Baseline in the Monthly Mean Total of Dysmenorrhea and Non-menstrual Pelvic Pain Scores
Description	Participants assessed dysmenorrhea and pelvic pain not related to menses and their impact on daily activities at approximately the same time every day on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe) in an e-Diary. The sum of the dysmenorrhea and non-menstrual pelvic pain scores on each day were calculated to create a daily total score. On days the participant was not having her period, the dysmenorrhea score was not defined; hence, the total score was equal to the non-menstrual pelvic pain score (range 0 to 3). On days where the participant recorded menstruation the total score ranged from 0 to 6, where higher scores indicate more severe pain. The monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores is the average of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and Weeks 4, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-0.18 (0.06)	-0.34 (0.06)	-0.29 (0.06)
Week 8	-0.18 (0.06)	-0.48 (0.06)	-0.33 (0.06)
Week 12	-0.27 (0.07)	-0.44 (0.06)	-0.41 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 4. Change from baseline in total of non-menstrual pelvic pain and dysmenorrhea scores was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0603
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 4. Change from baseline in total of non-menstrual pelvic pain and dysmenorrhea scores was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1855
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 8. Change from baseline in total of non-menstrual pelvic pain and dysmenorrhea scores was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.48 to -0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 8. Change from baseline in total of non-menstrual pelvic pain and dysmenorrhea scores was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1002
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at week 12. Change from baseline in total of non-menstrual pelvic pain and dysmenorrhea scores was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0568
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Difference = Elagolix - Placebo

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at week 12. Change from baseline in total of non-menstrual pelvic pain and dysmenorrhea scores was analyzed by a repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for subject, and the baseline-by-time interaction, and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1190
	Comments
	Method	Repeated Measures ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Difference = Elagolix - Placebo

7. Secondary Outcome

Title	Percentage of Days With No Pain Based on NRS
Description	The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The percentage of days a participant reported a value of zero (or "no pain") for the NRS was calculated for the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Baseline	27.600 (3.588)	25.380 (3.564)	25.515 (3.493)
Week 4	35.252 (4.118)	36.401 (4.606)	32.355 (4.604)
Week 8	40.861 (4.671)	43.780 (5.114)	36.737 (5.467)
Week 12	47.431 (4.955)	44.841 (5.857)	41.760 (5.796)

8. Secondary Outcome

Title	Percentage of Days With No Pain Based Based on Non-menstrual Pelvic Pain Daily Assessment
Description	Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time every day in an e-Diary according to the following response options: 0 = No pelvic pain 1 = Mild pelvic pain; subject could not do some of the things she usually does 2 = Moderate pelvic pain; subject could not do many of the things she usually does 3 = Severe pelvic pain; subject could not do most or all of the things she usually does. The percentage of days a participant reported a value of zero ("no pain") for non-menstrual pelvic pain was calculated for the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Baseline	34.939 (3.831)	36.821 (4.041)	38.530 (4.065)
Week 4	42.986 (4.229)	45.469 (4.968)	44.443 (4.905)
Week 8	46.228 (4.777)	54.967 (5.291)	47.524 (5.367)
Week 12	54.270 (4.768)	53.836 (6.077)	50.061 (5.496)

9. Secondary Outcome

Title	Percentage of Days With No Pain Based Based on Dysmenorrhea Daily Assessment
Description	Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day in an e-Diary according to the following response options: Subject is not having her period 0 = No pain related to period 1 = Mild pain related to period; subject could not do some of the things she usually does 2 = Moderate pain related to period; subject could not do many of the things she usually does = Severe pain related to period; subject could not do most of or all of the things she usually does. The percentage of days a participant reported a value of zero ("no pain") for dysmenorrhea was calculated for the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Baseline	26.350 (3.710)	14.340 (2.154)	21.086 (3.210)
Week 4	30.513 (4.435)	43.411 (5.775)	39.475 (5.509)
Week 8	35.057 (5.135)	56.952 (6.016)	67.411 (6.190)
Week 12	34.439 (5.000)	61.658 (6.717)	66.186 (6.336)

10. Secondary Outcome

Title	Percentage of Days With No Pain Based Based on Total Score of Non-menstrual Pelvic Pain and Dysmenorrhea Daily Assessment
Description	Participants assessed dysmenorrhea and pelvic pain not related to menses and their impact on daily activities at approximately the same time every day in an e-Diary on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The sum of the dysmenorrhea and non-menstrual pelvic pain scores on each day were calculated to create a daily total score. On days the participant was not having her period, the dysmenorrhea score was not defined; hence, the total score was equal to the non-menstrual pelvic pain score (range 0 to 3). On days where the participant recorded menstruation the total score ranged from 0 to 6, where higher scores indicate more severe pain. The percentage of days a participant reported a value of zero ("no pain") for the non-menstrual pelvic pain and dysmenorrhea total score was calculated for the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Baseline	33.009 (3.690)	32.940 (3.649)	35.967 (3.815)
Week 4	39.586 (4.058)	44.020 (4.825)	43.230 (4.844)
Week 8	43.961 (4.607)	53.526 (5.200)	47.108 (5.380)
Week 12	50.340 (4.552)	52.584 (5.999)	49.409 (5.494)

11. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Any Analgesic Use
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, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-4.8 (2.3)	-8.7 (2.3)	-6.8 (2.3)
Week 8	-5.8 (2.4)	-12.6 (2.4)	-10.4 (2.4)
Week 12	-6.1 (2.5)	-10.5 (2.4)	-13.9 (2.4)

12. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Prescription Analgesic Use
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, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-1.0 (1.2)	-4.0 (1.2)	-2.3 (1.2)
Week 8	-0.8 (1.4)	-3.2 (1.3)	-3.2 (1.4)
Week 12	-2.1 (1.6)	-2.6 (1.6)	-3.3 (1.6)

13. Secondary Outcome

Title	Change From Baseline in the Percentage of Days of Narcotic Analgesic Use
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, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-0.8 (1.1)	-2.5 (1.2)	-2.1 (1.2)
Week 8	-0.8 (1.2)	-1.8 (1.2)	-3.0 (1.2)
Week 12	-1.7 (1.3)	-1.3 (1.3)	-3.6 (1.3)

14. Secondary Outcome

Title	Percentage of Participants With 30% Decrease From Baseline in Monthly Mean NRS
Description	The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	38.5 74%	43.1 84.5%	47.1 90.6%
Week 8	54.5 104.8%	60.4 118.4%	51.1 98.3%
Week 12	60.5 116.3%	63.6 124.7%	60.0 115.4%

15. Secondary Outcome

Title	Percentage of Participants With 30% Decrease From Baseline in Monthly Peak NRS
Description	The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	30.8 59.2%	35.3 69.2%	31.4 60.4%
Week 8	38.6 74.2%	43.8 85.9%	48.9 94%
Week 12	36.8 70.8%	47.7 93.5%	57.8 111.2%

16. Secondary Outcome

Title	Percentage of Participants With 50% Decrease From Baseline in Monthly Mean NRS
Description	The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	21.2 40.8%	37.3 73.1%	25.5 49%
Week 8	36.4 70%	45.8 89.8%	38.3 73.7%
Week 12	36.8 70.8%	45.5 89.2%	44.4 85.4%

17. Secondary Outcome

Title	Percentage of Participants With 50% Decrease From Baseline in Monthly Peak NRS
Description	The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit.
Time Frame	Baseline and weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	11.5 22.1%	17.6 34.5%	19.6 37.7%
Week 8	11.4 21.9%	25.0 49%	36.2 69.6%
Week 12	23.7 45.6%	34.1 66.9%	42.2 81.2%

18. Secondary Outcome

Title	Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS)
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess dyspareunia (painful intercourse) participants were asked to select the best description of pain during sexual intercourse over the past 28 days using the following response categories: 0 = Absent; No discomfort during sexual intercourse. 1 = Mild; I can tolerate the discomfort during sexual intercourse. 2 = Moderate; Intercourse is sometime interrupted due to pain. 3 = Severe; I prefer to avoid intercourse because of pain. Not applicable. I am not sexually active for reasons other than my endometriosis symptoms.
Time Frame	Baseline and Weeks 4, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	-0.19 (0.12)	-0.21 (0.12)	-0.56 (0.13)
Week 8	-0.15 (0.12)	-0.68 (0.12)	-0.66 (0.14)
Week 12	-0.29 (0.13)	-0.67 (0.12)	-0.49 (0.14)

19. Secondary Outcome

Title	Patient Global Impression of Change at Weeks 4, 8 and 12
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, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	3.4 (0.2)	3.0 (0.2)	2.8 (0.2)
Week 8	3.0 (0.2)	2.3 (0.1)	2.4 (0.2)
Week 12	3.2 (0.2)	2.2 (0.2)	2.2 (0.2)

20. Secondary Outcome

Title	Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved
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, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	54.2 104.2%	62.0 121.6%	80.0 153.8%
Week 8	67.4 129.6%	91.7 179.8%	84.4 162.3%
Week 12	60.0 115.4%	88.9 174.3%	82.2 158.1%

21. Secondary Outcome

Title	Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved
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, 8, and 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Week 4	12.5 24%	34.0 66.7%	38.0 73.1%
Week 8	37.0 71.2%	58.3 114.3%	60.0 115.4%
Week 12	32.5 62.5%	66.7 130.8%	62.2 119.6%

22. Secondary Outcome

Title	Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12
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 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 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 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and reported at least 10 e-Diary NRS values during the initial 12 week treatment period. The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	52	51	51
Pain	-11.8 (3.6)	-25.0 (3.3)	-17.3 (4.0)
Control and Powerlessness	-10.5 (4.7)	-25.6 (3.4)	-22.6 (4.8)
Emotional Wellbeing	-6.6 (4.0)	-17.2 (3.5)	-9.5 (4.8)
Social Support	-18.4 (4.2)	-25.0 (4.1)	-15.5 (4.8)
Self-image	-9.9 (3.1)	-18.9 (3.7)	-10.7 (4.0)
Work	-6.9 (4.2)	-28.8 (3.9)	-22.1 (3.2)
Relationship with Children	-7.0 (5.3)	-25.0 (4.4)	-20.3 (5.2)
Sexual Intercourse	-9.8 (4.6)	-23.1 (3.9)	-19.6 (5.5)
Medical Profession	0.0 (3.7)	-17.5 (3.9)	-14.0 (4.2)
Frustration with Treatment	-8.6 (4.7)	-26.2 (4.2)	-23.2 (5.4)
Concerns with Infertility	-9.8 (4.1)	-5.1 (4.1)	-9.1 (4.0)

23. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12
Description	Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and with available BMD data at baseline and week 12.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	37	42	43
Mean (Standard Deviation) [percent change]	-0.283 (1.851)	-0.294 (1.762)	-0.382 (1.338)

24. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24
Description	Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and with available BMD data at baseline and week 24.

Arm/Group Title	Elagolix 150 mg	Elagolix 250 mg	Placebo / Elagolix 150 mg	Placebo / Elagolix 250 mg
Arm/Group Description	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 150 mg for 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.
Measure Participants	37	37	13	17
Mean (Standard Deviation) [percent change]	-0.743 (1.877)	-1.024 (1.759)	-0.924 (1.198)	-0.076 (2.362)

25. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12
Description	Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and with available BMD data at baseline and week 12.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks.	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.
Measure Participants	36	43	42
Mean (Standard Deviation) [percent change]	0.375 (2.091)	-0.045 (2.088)	-0.937 (2.747)

26. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24
Description	Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of randomized, double-blind study drug and with available BMD data at baseline and week 24.

Arm/Group Title	Elagolix 150 mg	Elagolix 250 mg	Placebo / Elagolix 150 mg	Placebo / Elagolix 250 mg
Arm/Group Description	Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks.	Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 150 mg for 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.
Measure Participants	38	37	14	15
Mean (Standard Deviation) [percent change]	-1.032 (1.983)	-1.631 (2.874)	-0.692 (1.724)	0.681 (2.720)

Adverse Events

Time Frame	From the first dose of any study drug through week 24. The Placebo treatment group includes data for the initial 12-week treatment phase. The Elagolix treatment groups include data for the total 24-week treatment period for participants initially randomized to elagolix, and 12-week treatment period for participants initially randomized to placebo and re-randomized at week 12.
Arm/Group Title	Placebo		Elagolix 150 mg		Elagolix 250 mg
Arm/Group Description	Participants received elagolix 150 mg tablets once a day for 12 weeks.		Participants initially randomized to elagolix 150 mg received elagolix 150 mg tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg for an additional 12 weeks. Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 150 mg for 12 weeks.		Participants initially randomized to elagolix 250 mg received elagolix 250 mg tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks. Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.
All Cause Mortality
	Placebo		Elagolix 150 mg		Elagolix 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/69 (0%)		0/72 (0%)
Serious Adverse Events
	Placebo		Elagolix 150 mg		Elagolix 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/69 (0%)		1/72 (1.4%)
Pregnancy, puerperium and perinatal conditions
ABORTION SPONTANEOUS	0/52 (0%)	0	0/69 (0%)	0	1/72 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Elagolix 150 mg		Elagolix 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/52 (34.6%)		31/69 (44.9%)		33/72 (45.8%)
Gastrointestinal disorders
NAUSEA	1/52 (1.9%)	1	6/69 (8.7%)	7	6/72 (8.3%)	6
Infections and infestations
NASOPHARYNGITIS	3/52 (5.8%)	3	2/69 (2.9%)	4	3/72 (4.2%)	4
SINUSITIS	2/52 (3.8%)	2	6/69 (8.7%)	6	2/72 (2.8%)	2
UPPER RESPIRATORY TRACT INFECTION	3/52 (5.8%)	3	6/69 (8.7%)	6	4/72 (5.6%)	4
URINARY TRACT INFECTION	2/52 (3.8%)	2	5/69 (7.2%)	5	4/72 (5.6%)	4
VAGINAL MYCOSIS	3/52 (5.8%)	3	1/69 (1.4%)	1	6/72 (8.3%)	8
Investigations
BLOOD CHOLESTEROL INCREASED	0/52 (0%)	0	4/69 (5.8%)	4	0/72 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	4/52 (7.7%)	5	3/69 (4.3%)	3	5/72 (6.9%)	5
BACK PAIN	2/52 (3.8%)	2	4/69 (5.8%)	4	2/72 (2.8%)	2
Nervous system disorders
HEADACHE	1/52 (1.9%)	1	6/69 (8.7%)	9	4/72 (5.6%)	12
MIGRAINE	0/52 (0%)	0	3/69 (4.3%)	3	4/72 (5.6%)	4
Skin and subcutaneous tissue disorders
ACNE	1/52 (1.9%)	1	0/69 (0%)	0	6/72 (8.3%)	6

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.