Efficacy and Safety Study of Elagolix Versus Placebo or Leuprorelin Acetate in Endometriosis

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT00797225

Collaborator

(none)

174

Enrollment

Arms

14.9

Actual Duration (Months)

Study Details

Study Description

Brief Summary

This study is designed to evaluate the safety and beneficial effects of elagolix (NBI-56418) compared to placebo and leuprorelin (an approved endometriosis therapy) over a three month period followed by an additional three months of treatment on elagolix.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis	Drug: Leuprorelin Acetate Depot Drug: Elagolix Drug: Placebo to Elagolix Drug: Placebo to Leuprorelin Acetate	Phase 2

Detailed Description

The study followed a parallel-group design in which participants were randomized (1:1:1:1) to one of the following treatment groups for the first 12 weeks of dosing: 150 mg elagolix once daily (q.d.); 250 mg elagolix q.d.; placebo; or leuprorelin acetate depot injection 3.75 mg (monthly). Blinding was achieved using a double-dummy design. Following 12 weeks of dosing, participants continued in the study for an additional 12 weeks; participants randomized to elagolix continued to receive their assigned dose and participants randomized to placebo or leuprorelin acetate were re-randomized to receive one of the two doses of elagolix (150 mg q.d. or 250 mg q.d.) for 12 weeks in a double-blind fashion. Six weeks after the last dose of the study drug at the end of Week 24, a follow-up visit was performed (end of Week 30).

There was no pre-specified primary efficacy end point as there was no single key efficacy outcome measure in this exploratory Phase 2 study. For purposes of results reported here, Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain is designated as the primary outcome measure.

Study Design

Study Type:

Interventional

Actual Enrollment :

174 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- and Active-Controlled Study to Assess the Efficacy and Safety of NBI-56418 in Subjects With Endometriosis

Actual Study Start Date :

Nov 26, 2008

Actual Primary Completion Date :

Feb 24, 2010

Actual Study Completion Date :

Feb 24, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Drug: Placebo to Elagolix Placebo tablet administered orally Drug: Placebo to Leuprorelin Acetate Saline solution administered as an intramuscular injection
Experimental: Elagolix 150 mg Participants 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.	Drug: Elagolix Elagolix tablets administered orally Other Names: NBI-56418 Orilissa™ Drug: Placebo to Leuprorelin Acetate Saline solution administered as an intramuscular injection
Experimental: Elagolix 250 mg Participants 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.	Drug: Elagolix Elagolix tablets administered orally Other Names: NBI-56418 Orilissa™ Drug: Placebo to Leuprorelin Acetate Saline solution administered as an intramuscular injection
Other: Leuprorelin Participants received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.	Drug: Leuprorelin Acetate Depot Leuprorelin acetate depot injection 3.75 mg administered as an intramuscular injection Other Names: Prostap SR Drug: Placebo to Elagolix Placebo tablet administered orally

Outcome Measures

Primary Outcome Measures

Change From Baseline in the Monthly Mean 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 mean NRS is the average of the daily values reported during the 4 weeks prior to each visit.

Secondary Outcome Measures

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.
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.
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 of their period 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.
Change From Baseline in the Monthly Mean Sum 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 dysmenorrhea scale included an option for participants who were not having their period. 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.
Change From Baseline in the Percentage of Days of Any Analgesic Use [Baseline, 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").
Change From Baseline in the Percentage of Days of Prescription Analgesic Use [Baseline, 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").
Change From Baseline in the Percentage of Days of Narcotic Analgesic Use [Baseline, 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").
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.
Change From Baseline in Dysmenorrhea Component of the CPSSS [Baseline and Week 12]
The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess dysmenorrhea (pain during menstruation), participants were asked to select the best description of painful menstruation over the past 28 days using the following response categories: 0 = Absent; Amenorrhea (no bleeding) or no discomfort. 1 = Mild; Some loss of work efficiency; occasional use of analgesics. 2 = Moderate; In bed part of one day, occasional loss of work; regular use of analgesics. 3 = Severe; In bed ≥ 1 day, incapacitation; requirement for strong analgesics.
Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component [Baseline and Week 12]
The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess non-menstrual pelvic pain, participants were asked to select the best description of pelvic pain over the past 28 days using the following response categories: 0 = Absent; No discomfort. 1 = Mild; Occasional pelvic discomfort that can be treated with NSAIDs. 2 = Moderate; Noticeable discomfort or pain for most of cycle requiring regular use of NSAID or weak opiate. 3 = Severe; Pain persisting during the cycle or pain requiring strong analgesics.
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
Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved [Weeks 4, 8 and 12]
The 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
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved [Weeks 4, 8 and 12]
The 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
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.
Concentration of Serum Estradiol [Baseline and Weeks 4, 8 and 12]
The concentration of serum estradiol (E2) was quantified using liquid chromatography with tandem mass spectrophotometry (LC/MS/MS). Serum estradiol concentrations below the limit of quantification (BLQ) were set equal to the lower limit of quantification (2.5 pg/mL).
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).
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).
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).
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).
Change From Baseline in Serum N-telopeptide Concentration at Week 12 [Baseline and week 12]
Blood samples to determine N-telopeptide concentrations were analyzed by a central laboratory using an enzyme-linked immunosorbent assay (ELISA).
Average Number of Hot Flashes Per Day [Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups)]
Hot flashes, if any, were reported daily by participants during the study using the e-Diary. The average number of hot flashes per day was calculated for each participant as the total number of hot flashes divided by total days in the phase.
Percentage of Days With Uterine Bleeding [Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups)]
Uterine bleeding was reported daily by participants during the study using the e-Diary. The percentage of days a participant reported any bleeding was calculated as the total number of days the participant reported any bleeding ( light, moderate, or heavy) divided by the total number of days the participant had a non-missing eDiary report of vaginal bleeding in the phase.
Number of Days to First Posttreatment Menses [From last day of study drug up to 6 weeks after the last dose.]
Defined as the number of days from the last dose of study drug until the start date of the first post-treatment menses.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria

Female, aged 18 to 45 years, inclusive
Have moderate to severe pelvic pain due to endometriosis
Have been surgically (laparoscopy) diagnosed with endometriosis within the last 5 years and have recurrent or persistent endometriosis symptoms
Have regular menstrual cycle (23-33 day)
Agree to use two forms of non-hormonal contraception during the study

Exclusion Criteria:

Received a Gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening.
Received subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular (i.m.) medroxyprogesterone acetate (DMPA-IM), or have received either 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
Are using systemic steroids on a chronic or regular basis within 3 months
Have uterine fibroids or other pelvic lesions ≥ 3 cm in diameter
Have had a hysterectomy or oophorectomy
Have pelvic pain that is not caused by endometriosis
Have unstable medical condition or chronic disease
Have been pregnant within the last 6 months and is 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:

NCT00797225

Other Study ID Numbers:

NBI-56418-0703
2007-006474-28

First Posted:

Nov 25, 2008

Last Update Posted:

Sep 10, 2018

Last Verified:

Apr 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by AbbVie

bone mineral density,endometriosis,pelvic pain

Additional relevant MeSH terms:

Endometriosis

Leuprolide

Study Results

Participant Flow

Recruitment Details	The study was conducted from 26 November 2008 to 24 February 2010 at 27 centers in Central Eastern Europe (Bulgaria, Hungary, Poland, Romania, Russia and Ukraine).
Pre-assignment Detail	Patients were randomized equally to oral elagolix 150 mg or 250 mg once daily, placebo or leuprorelin acetate (LA) 1-month depot 3.75 mg injection for 12 weeks. Thereafter, patients originally randomized to placebo or LA were re-randomized to 1 of the elagolix doses and patients randomized to elagolix continued their assigned dose for 12 weeks.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin	Placebo / Elagolix 150 mg	Placebo / Elagolix 250 mg	Leuprorelin / Elagolix 150 mg	Leuprorelin / Elagolix 250 mg
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 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.	Participants initially randomized to leuprorelin acetate were re-randomized at week 12 to receive elagolix 150 mg for 12 weeks.	Participants initially randomized to leuprorelin acetate were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.
Period Title: Weeks 1 to 12
STARTED	43	43	44	44	0	0	0	0
Received Study Drug	43	43	44	44	0	0	0	0
COMPLETED	41	42	43	44	0	0	0	0
NOT COMPLETED	2	1	1	0	0	0	0	0
Period Title: Weeks 1 to 12
STARTED	0	42	43	0	20	21	22	22
COMPLETED	0	38	41	0	19	21	20	22
NOT COMPLETED	0	4	2	0	1	0	2	0

Baseline Characteristics

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin	Total
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.	Total of all reporting groups
Overall Participants	43	43	44	44	174
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.4 (0.8)	32.1 (0.9)	31.7 (1.0)	31.4 (0.7)	31.7 (0.4)
Sex: Female, Male (Count of Participants)
Female	43 100%	43 100%	44 100%	44 100%	174 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	43 100%	43 100%	44 100%	44 100%	174 100%

Outcome Measures

1. Primary 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, 8, and 12

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	-0.35 (0.17)	-0.84 (0.17)	-1.00 (0.17)	-0.94 (0.17)
Week 8	-0.93 (0.20)	-1.25 (0.20)	-1.57 (0.20)	-1.55 (0.20)
Week 12	-1.22 (0.21)	-1.34 (0.21)	-1.47 (0.21)	-1.81 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 4. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0464
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95% -0.98 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.25
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 4. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0080
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95% -1.13 to -0.17
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.24
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 4. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0159
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95% -1.08 to -0.11
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.24
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 8. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2563
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95% -0.89 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.29
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 8. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0239
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95% -1.21 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.28
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 8. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0280
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95% -1.19 to -0.07
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.28
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 12. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6904
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95% -0.70 to 0.46
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.29
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 12. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4022
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95% -0.83 to 0.33
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.29
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 12. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0451
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95% -1.17 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.29
	Estimation Comments

2. 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	-0.20 (0.34)	-1.82 (0.34)	-1.83 (0.33)	-1.48 (0.33)
Week 8	-0.89 (0.34)	-2.23 (0.34)	-2.96 (0.33)	-3.62 (0.33)
Week 12	-1.67 (0.34)	-2.62 (0.34)	-3.05 (0.34)	-3.99 (0.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 4. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.62
	Confidence Interval	(2-Sided) 95% -2.56 to -0.69
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.48
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 4. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.63
	Confidence Interval	(2-Sided) 95% -2.56 to -0.70
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.47
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 4. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0073
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.28
	Confidence Interval	(2-Sided) 95% -2.21 to -0.35
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.47
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 8. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0054
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.34
	Confidence Interval	(2-Sided) 95% -2.28 to -0.40
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.48
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 8. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.07
	Confidence Interval	(2-Sided) 95% -3.01 to -1.12
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.48
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 8. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.73
	Confidence Interval	(2-Sided) 95% -3.67 to -1.79
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.48
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 12. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0509
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 95% -1.89 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.48
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 12. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0046
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS mean Difference
	Estimated Value	-1.38
	Confidence Interval	(2-Sided) 95% -2.33 to -0.43
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.48
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 12. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.32
	Confidence Interval	(2-Sided) 95% -3.26 to -1.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.48
	Estimation Comments

3. 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	-0.05 (0.06)	-0.22 (0.06)	-0.21 (0.06)	-0.27 (0.06)
Week 8	-0.18 (0.06)	-0.34 (0.06)	-0.36 (0.06)	-0.46 (0.06)
Week 12	-0.30 (0.06)	-0.35 (0.06)	-0.34 (0.06)	-0.55 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 4. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0453
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95% -0.33 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 4. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0609
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95% -0.31 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 4. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0069
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95% -0.38 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 8. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0556
	Comments
	Method	Mixed-effects Repeated Measures Model]
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95% -0.32 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 8. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0387
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95% -0.33 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 8. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95% -0.44 to -0.12
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 12. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5879
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -0.21 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 12. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6122
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -0.20 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 12. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0023
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95% -0.41 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.08
	Estimation Comments

4. 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 of their period 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	-0.17 (0.08)	-0.64 (0.08)	-0.67 (0.08)	-0.65 (0.08)
Week 8	-0.40 (0.08)	-0.86 (0.08)	-1.04 (0.08)	-1.22 (0.08)
Week 12	-0.35 (0.08)	-0.76 (0.08)	-0.87 (0.08)	-1.14 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 4. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95% -0.69 to -0.24
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 4. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS mean Difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95% -0.73 to -0.27
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 4. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95% -0.71 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 8. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95% -0.69 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 8. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS mean Difference
	Estimated Value	-0.64
	Confidence Interval	(2-Sided) 95% -0.87 to -0.40
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 8. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95% -1.04 to -0.59
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 12. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95% -0.65 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 12. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95% -0.76 to -0.29
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 12. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95% -1.02 to -0.56
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.12
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in the Monthly Mean Sum 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 dysmenorrhea scale included an option for participants who were not having their period. 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	-0.12 (0.07)	-0.43 (0.07)	-0.44 (0.07)	-0.50 (0.07)
Week 8	-0.24 (0.07)	-0.58 (0.07)	-0.67 (0.07)	-0.78 (0.07)
Week 12	-0.40 (0.07)	-0.55 (0.07)	-0.63 (0.07)	-0.87 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 4. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95% -0.51 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 4. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95% -0.51 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 4. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95% -0.57 to -0.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 8. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	-0.33
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95% -0.52 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 8. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95% -0.62 to -0.24
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 8. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95% -0.73 to -0.35
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments	Analysis at Week 12. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1319
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95% -0.34 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 250 mg
	Comments	Analysis at Week 12. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0222
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95% -0.42 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Leuprorelin
	Comments	Analysis at Week 12. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects Repeated Measures Model
	Comments

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95% -0.66 to -0.28
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.10
	Estimation Comments

6. 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, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	-5.2 (2.0)	-1.1 (2.0)	-8.4 (2.0)	-8.7 (2.0)
Week 8	-6.2 (2.0)	-3.4 (2.0)	-9.1 (2.0)	-10.2 (2.0)
Week 12	-6.2 (2.0)	-4.4 (2.0)	-8.3 (2.0)	-10.5 (2.0)

7. 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, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	-0.3 (1.8)	3.4 (1.8)	-1.2 (1.7)	-2.5 (1.7)
Week 8	-1.3 (1.6)	1.3 (1.6)	-2.8 (1.6)	-2.6 (1.6)
Week 12	-1.8 (1.4)	0.7 (1.4)	-1.9 (1.4)	-2.8 (1.3)

8. 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, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	0.0 (0.1)	-0.1 (0.1)	0.0 (0.1)	-0.1 (0.1)
Week 8	-0.1 (0.1)	-0.1 (0.1)	-0.1 (0.1)	-0.1 (0.1)
Week 12	0.0 (0.1)	0.1 (0.1)	0.1 (0.1)	0.3 (0.1)

9. 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at baseline and at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	40	38	40	41
Week 4	-0.33 (0.11)	-0.46 (0.11)	-0.49 (0.11)	-0.55 (0.11)
Week 8	-0.72 (0.11)	-0.68 (0.11)	-0.77 (0.11)	-0.76 (0.11)
Week 12	-0.60 (0.11)	-0.84 (0.12)	-0.89 (0.11)	-1.04 (0.11)

10. Secondary Outcome

Title	Change From Baseline in Dysmenorrhea Component of the CPSSS
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess dysmenorrhea (pain during menstruation), participants were asked to select the best description of painful menstruation over the past 28 days using the following response categories: 0 = Absent; Amenorrhea (no bleeding) or no discomfort. 1 = Mild; Some loss of work efficiency; occasional use of analgesics. 2 = Moderate; In bed part of one day, occasional loss of work; regular use of analgesics. 3 = Severe; In bed ≥ 1 day, incapacitation; requirement for strong analgesics.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). Data collection for this endpoint was added via a protocol amendment; therefore, the analysis only includes the subset of participants affected by the protocol amendment.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	20	19	23	24
Least Squares Mean (Standard Error) [units on a scale]	-1.03 (0.17)	-1.29 (0.17)	-1.47 (0.16)	-1.75 (0.15)

11. Secondary Outcome

Title	Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess non-menstrual pelvic pain, participants were asked to select the best description of pelvic pain over the past 28 days using the following response categories: 0 = Absent; No discomfort. 1 = Mild; Occasional pelvic discomfort that can be treated with NSAIDs. 2 = Moderate; Noticeable discomfort or pain for most of cycle requiring regular use of NSAID or weak opiate. 3 = Severe; Pain persisting during the cycle or pain requiring strong analgesics.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). Data collection for this endpoint was added via a protocol amendment; therefore, the analysis only includes the subset of participants affected by the protocol amendment.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	20	19	23	24
Least Squares Mean (Standard Error) [units on a scale]	-0.60 (0.12)	-0.58 (0.12)	-0.48 (0.11)	-0.79 (0.11)

12. 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	3.4 (0.1)	3.0 (0.1)	2.9 (0.2)	3.3 (0.1)
Week 8	2.8 (0.1)	2.5 (0.2)	2.2 (0.1)	2.3 (0.1)
Week 12	2.6 (0.2)	2.4 (0.1)	2.2 (0.2)	2.1 (0.1)

13. Secondary Outcome

Title	Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved
Description	The 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	56.1 130.5%	74.4 173%	65.1 148%	50.0 113.6%
Week 8	75.6 175.8%	81.4 189.3%	90.7 206.1%	88.6 201.4%
Week 12	80.5 187.2%	88.1 204.9%	88.4 200.9%	93.2 211.8%

14. Secondary Outcome

Title	Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved
Description	The 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Week 4	7.3 17%	25.6 59.5%	32.6 74.1%	27.3 62%
Week 8	36.6 85.1%	53.5 124.4%	72.1 163.9%	54.5 123.9%
Week 12	53.7 124.9%	54.8 127.4%	67.4 153.2%	70.5 160.2%

15. 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 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data for each dimension at baseline and week 12.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Pain	-14.0 (4.8)	-19.0 (4.1)	-25.0 (4.7)	-31.8 (3.9)
Control and Powerlessness	-18.3 (4.4)	-17.9 (3.9)	-20.9 (5.1)	-23.9 (4.9)
Emotional Wellbeing	-14.6 (4.2)	-10.7 (4.1)	-12.8 (4.4)	-13.6 (4.4)
Social Support	-22.0 (4.4)	-16.1 (4.4)	-18.6 (5.6)	-15.3 (5.1)
Self-image	-12.2 (6.5)	-7.7 (4.5)	-5.8 (5.0)	-8.5 (4.1)
Work	-23.7 (3.9)	-21.5 (4.5)	-29.9 (5.1)	-38.6 (4.3)
Relationship with Children	-11.5 (6.7)	-15.3 (5.4)	-25.0 (7.6)	-22.9 (9.5)
Sexual Intercourse	-32.2 (5.7)	-21.2 (6.2)	-30.6 (5.3)	-28.9 (5.7)
Medical Profession	-5.3 (4.5)	-5.5 (4.0)	-7.6 (3.0)	-6.3 (4.2)
Frustration with Treatment	-11.4 (6.1)	-10.9 (6.3)	-7.6 (6.9)	-12.5 (6.9)
Concerns with Infertility	-19.7 (5.0)	-24.0 (7.0)	-13.8 (5.2)	-13.3 (4.8)

16. Secondary Outcome

Title	Concentration of Serum Estradiol
Description	The concentration of serum estradiol (E2) was quantified using liquid chromatography with tandem mass spectrophotometry (LC/MS/MS). Serum estradiol concentrations below the limit of quantification (BLQ) were set equal to the lower limit of quantification (2.5 pg/mL).
Time Frame	Baseline and Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description
Randomized participants who received at least one dose of randomized, double-blind study drug with at least one eDiary value following randomization, excluding participants who had less than 80% oral study drug dosing compliance during Weeks 1-12 (per protocol population). The analysis includes participants with non-missing data at each time point.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	41	43	44
Baseline	39.10	43.40	47.50	46.20
Week 4	49.50	36.40	22.00	3.63
Week 8	61.00	36.90	23.65	4.36
Week 12	87.90	36.70	26.20	6.38

17. 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
Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) and with available BMD data at baseline and week 12.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	40	41	42	43
Mean (Standard Deviation) [percent change]	-0.90 (1.316)	-0.342 (1.583)	-0.5623 (1.367)	-1.122 (1.634)

18. 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
Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) and with available BMD data at baseline and week 12.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	40	41	42	44
Mean (Standard Deviation) [percent change]	0.106 (1.893)	-1.053 (1.985)	-0.799 (2.352)	-1.633 (2.113)

19. 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
Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) 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	Leuprorelin / Elagolix 150 mg	Leuprorelin / Elagolix 250 mg
Arm/Group Description	Participants 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 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 150 mg for 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.	Participants initially randomized to leuprorelin acetate were re-randomized at week 12 to receive elagolix 150 mg for 12 weeks.	Participants initially randomized to leuprorelin acetate were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.
Measure Participants	36	38	17	20	18	21
Mean (Standard Deviation) [percent change]	-0.549 (1.827)	-0.699 (1.574)	-0.126 (1.732)	-0.573 (1.328)	-1.784 (1.571)	-1.783 (2.096)

20. 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
Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) 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	Leuprorelin / Elagolix 150 mg	Leuprorelin / Elagolix 250 mg
Arm/Group Description	Participants 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 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 150 mg for 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.	Participants initially randomized to leuprorelin acetate were re-randomized at week 12 to receive elagolix 150 mg for 12 weeks.	Participants initially randomized to leuprorelin acetate were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.
Measure Participants	35	39	17	20	18	21
Mean (Standard Deviation) [percent change]	-1.288 (2.681)	-1.855 (2.670)	-0.990 (2.636)	-0.648 (2.377)	-2.899 (2.733)	-4.378 (2.099)

21. Secondary Outcome

Title	Change From Baseline in Serum N-telopeptide Concentration at Week 12
Description	Blood samples to determine N-telopeptide concentrations were analyzed by a central laboratory using an enzyme-linked immunosorbent assay (ELISA).
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description
Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) and with available data at baseline and week 12.

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	39	43	41	40
Mean (Standard Error) [nM bone collagen equivalents (BCE)]	0.62 (0.78)	0.77 (0.69)	2.04 (0.66)	3.18 (0.72)

22. Secondary Outcome

Title	Average Number of Hot Flashes Per Day
Description	Hot flashes, if any, were reported daily by participants during the study using the e-Diary. The average number of hot flashes per day was calculated for each participant as the total number of hot flashes divided by total days in the phase.
Time Frame	Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups)

Outcome Measure Data

Analysis Population Description
Participants who received at least one dose of randomized, double-blind study drug (safety analysis set).

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Screening	0.00	0.00	0.00	0.00
Treatment Phase	0.11	0.22	1.10	1.73

23. Secondary Outcome

Title	Percentage of Days With Uterine Bleeding
Description	Uterine bleeding was reported daily by participants during the study using the e-Diary. The percentage of days a participant reported any bleeding was calculated as the total number of days the participant reported any bleeding ( light, moderate, or heavy) divided by the total number of days the participant had a non-missing eDiary report of vaginal bleeding in the phase.
Time Frame	Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups)

Outcome Measure Data

Analysis Population Description
Participants who received at least one dose of randomized, double-blind study drug (safety analysis set).

Arm/Group Title	Placebo	Elagolix 150 mg	Elagolix 250 mg	Leuprorelin
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks.	Participants 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 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 received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks.
Measure Participants	43	43	44	44
Screening	21.10 (1.78)	18.32 (1.14)	22.32 (1.68)	21.05 (1.87)
Treatment Phase	21.46 (1.39)	10.78 (1.14)	9.54 (1.35)	11.04 (1.30)

24. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Elagolix 150 mg	Elagolix 250 mg	Placebo / Elagolix 150 mg	Placebo / Elagolix 250 mg	Leuprorelin / Elagolix 150 mg	Leuprorelin / Elagolix 250 mg
Arm/Group Description	Participants 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 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 150 mg for 12 weeks.	Participants initially randomized to placebo were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.	Participants initially randomized to leuprorelin acetate were re-randomized at week 12 to receive elagolix 150 mg for 12 weeks.	Participants initially randomized to leuprorelin acetate were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.
Measure Participants	38	39	19	20	20	21
Median (Full Range) [days]	22.5	26.0	26.0	27.0	29.0	28.0

Adverse Events

	Placebo		Elagolix 150 mg		Elagolix 250 mg		Leuprorelin Acetate
Time Frame	From the first dose of any study drug through week 30. The Placebo and Leuprorelin treatment groups include data for the initial 12-week treatment phase. The Elagolix treatment groups include data for the 24 week treatment period plus 6 weeks follow-up for participants initially randomized to elagolix, and 12 week treatment period plus 6-week follow-up for participants initially randomized to placebo or leuprorelin and were re-randomized at week 12.
Adverse Event Reporting Description

Arm/Group Title	Placebo		Elagolix 150 mg		Elagolix 250 mg		Leuprorelin Acetate
Arm/Group Description	Participants received placebo tablets once a day and placebo intramuscular injection once a month 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 or leuprorelin 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 or leuprorelin were re-randomized at week 12 to receive elagolix 250 mg for 12 weeks.		Participants received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month for 12 weeks.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/85 (0%)		0/87 (0%)		0/44 (0%)
Serious Adverse Events
	Placebo		Elagolix 150 mg		Elagolix 250 mg		Leuprorelin Acetate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		1/85 (1.2%)		2/87 (2.3%)		0/44 (0%)
Infections and infestations
APPENDICITIS	0/43 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1	0/44 (0%)	0
Metabolism and nutrition disorders
DIABETES MELLITUS NON-INSULIN-DEPENDENT	0/43 (0%)	0	1/85 (1.2%)	1	0/87 (0%)	0	0/44 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PARANASAL SINUS BENIGN NEOPLASM	0/43 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1	0/44 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Elagolix 150 mg		Elagolix 250 mg		Leuprorelin Acetate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/43 (7%)		25/85 (29.4%)		21/87 (24.1%)		6/44 (13.6%)
Ear and labyrinth disorders
VERTIGO	1/43 (2.3%)	1	6/85 (7.1%)	6	2/87 (2.3%)	2	0/44 (0%)	0
Gastrointestinal disorders
NAUSEA	1/43 (2.3%)	1	6/85 (7.1%)	6	5/87 (5.7%)	5	0/44 (0%)	0
Investigations
BONE DENSITY DECREASED	0/43 (0%)	0	7/85 (8.2%)	7	6/87 (6.9%)	6	0/44 (0%)	0
Nervous system disorders
HEADACHE	2/43 (4.7%)	2	11/85 (12.9%)	21	10/87 (11.5%)	12	6/44 (13.6%)	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.

Results Point of Contact

Name/Title	Global Medical Services
Organization	AbbVie
Phone	800-633-9110
Email

Responsible Party:

AbbVie

ClinicalTrials.gov Identifier:

NCT00797225

Other Study ID Numbers:

NBI-56418-0703
2007-006474-28

First Posted:

Nov 25, 2008

Last Update Posted:

Sep 10, 2018

Last Verified:

Apr 1, 2018