Elagolix Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis (PETAL)

• ClinicalTrials.gov Identifier: NCT00437658
• Recruitment Status: Completed
• First Posted: February 21, 2007
• Results First Posted: October 12, 2018
• Last Update Posted: October 12, 2018
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Endometriosis
• Interventions: Drug: Elagolix; Drug: Subcutaneous depot medroxyprogesterone acetate (DMPA-SC); Drug: Placebo to Elagolix; Drug: Placebo to DMPA-SC
• Enrollment: 252

Participant Flow

Recruitment Details	Participants were randomized at 58 centers in the United States.
Pre-assignment Details	This study consisted of a 24-week treatment period and a 24-week post-treatment period. Participants were randomized in a 1:1:1 ratio to one of three treatment groups.

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Period Title: Treatment Period (24 Weeks)
Started	84	84	84
Received Study Drug	84	84	84
Completed	56	62	51
Not Completed	28	22	33
Reason Not Completed
Adverse Event	4	7	14
Non-compliance	1	1	4
Withdrawal by Subject	9	7	7
Lack of Efficacy	4	2	3
Lost to Follow-up	5	4	5
Sponsor/Investigator Decision	5	1	0
Period Title: Post-treatment Period (24 Weeks)
Started	56	62	51
Completed	32	54	37
Not Completed	24	8	14
Reason Not Completed
Adverse Event	1	0	1
Non-compliance	3	0	1
Withdrawal by Subject	12	6	8
Lack of Efficacy	0	2	2
Lost to Follow-up	5	0	1
Sponsor/Investigator Decision	3	0	1

Baseline Characteristics

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC	Total
Arm/Group Description		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.	Total of all reporting groups
Overall Number of Baseline Participants		84	84	84	252
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	84 participants	84 participants	84 participants	252 participants
		32.4 (7.5)	31.4 (6.1)	30.9 (6.3)	31.6 (6.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	84 participants	84 participants	84 participants	252 participants
	Female	84 100.0%	84 100.0%	84 100.0%	252 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	84 participants	84 participants	84 participants	252 participants
	Asian	1 1.2%	0 0.0%	1 1.2%	2 0.8%
	Black	6 7.1%	10 11.9%	10 11.9%	26 10.3%
	White	68 81.0%	70 83.3%	65 77.4%	203 80.6%
	Hispanic	8 9.5%	4 4.8%	6 7.1%	18 7.1%
	American Indian or Alaska Native, Caucasian	0 0.0%	0 0.0%	1 1.2%	1 0.4%
	Black, Caucasian	1 1.2%	0 0.0%	0 0.0%	1 0.4%
	Caucasian, Hispanic	0 0.0%	0 0.0%	1 1.2%	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24
Description	Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in spine and femur BMD at week 24 was assessed using a one-way analysis of variance (ANOVA) model. The absence of significant bone loss was supported if the lower bounds of the confidence intervals for the mean percent change in BMD were ≥ -2.2% for both the spine and femur at week 24.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose (i.e., one tablet or injection) of study drug (safety analysis set) with available BMD data at both time points

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed	55	62	50
Least Squares Mean (95% Confidence Interval); Unit of Measure: percent change
	-0.11; (-0.70 to 0.48)	-1.29; (-1.85 to -0.74)	-0.99; (-1.61 to -0.37)

2. Primary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24
Description	Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in spine and femur BMD at week 24 was assessed using a one-way analysis of variance (ANOVA) model. The absence of significant bone loss was supported if the lower bounds of the confidence intervals for the mean percent change in BMD were ≥ -2.2% for both the spine and femur at week 24.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose (i.e., one tablet or injection) of study drug (safety analysis set) with available BMD data at both time points

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed	56	64	51
Least Squares Mean (95% Confidence Interval); Unit of Measure: percent change
	-0.47; (-0.96 to 0.02)	-1.02; (-1.48 to -0.56)	-1.29; (-1.80 to -0.77)

3. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Spine at Weeks 12 and 48
Description	Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD was assessed using a one-way analysis of variance (ANOVA) model.
Time Frame	Baseline and weeks 12 and 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose (i.e., one tablet or injection) of study drug (safety analysis set) with available BMD data at each time point

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	84
Least Squares Mean (95% Confidence Interval); Unit of Measure: percent change
Week 12	Number Analyzed	68 participants	68 participants	67 participants
		-0.39; (-0.80 to 0.02)	-1.05; (-1.46 to -0.64)	-0.57; (-0.98 to -0.15)
Week 48	Number Analyzed	34 participants	56 participants	40 participants
		0.20; (-0.57 to 0.96)	-0.49; (-1.09 to 0.10)	-0.56; (-1.27 to 0.15)

4. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density of the Femur at Weeks 12 and 48
Description	Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in BMD was assessed using a one-way analysis of variance (ANOVA) model.
Time Frame	Baseline and weeks 12 and 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose (i.e., one tablet or injection) of study drug (safety analysis set) with available BMD data at each time point

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	84
Least Squares Mean (95% Confidence Interval); Unit of Measure: percent change
Week 12	Number Analyzed	67 participants	70 participants	68 participants
		-0.63; (-1.02 to -0.24)	-0.54; (-0.92 to -0.17)	-0.77; (-1.16 to -0.39)
Week 48	Number Analyzed	33 participants	57 participants	39 participants
		-0.38; (-1.10 to 0.33)	-0.86; (-1.41 to -0.32)	-0.76; (-1.42 to -0.10)

5. Secondary Outcome

Title	Change From Baseline in N-telopeptide at Weeks 12, 24 and 48
Description	Blood samples to determine N-telopeptide concentrations were analyzed by a central laboratory using an enzyme-linked immunosorbent assay (ELISA). Change from baseline in N-telopeptide was analyzed using a one-way ANOVA model.
Time Frame	Baseline and weeks 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose (i.e., one tablet or injection) of study drug (safety analysis set) with available BMD data at each time point

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	84
Least Squares Mean (Standard Error); Unit of Measure: nM bone collagen equivalents (BCE)
Week 12	Number Analyzed	70 participants	68 participants	63 participants
		0.94 (0.43)	0.57 (0.43)	0.74 (0.45)
Week 24	Number Analyzed	57 participants	61 participants	49 participants
		0.23 (0.50)	-0.30 (0.48)	-0.24 (0.54)
Week 48	Number Analyzed	33 participants	52 participants	36 participants
		-1.28 (0.61)	-1.53 (0.48)	-1.39 (0.58)

6. Secondary Outcome

Title	Percentage of Participants With a Response in the Dysmenorrhea Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) at Week 24
Description	The CPSSS consists of 5 components that address dysmenorrhea (pain during menstruation), dyspareunia (painful intercourse), non-menstrual pelvic pain, pelvic tenderness, and pelvic induration (hardening). Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The dysmenorrhea score was based on the participant's response to the question "Have you had painful menstruation during the last 28 days?". Participants were classified as responders for dysmenorrhea if they reported a 1 point or greater reduction (improvement) from baseline.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary visual analog scale (VAS) values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data.

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed	57	65	51
Measure Type: Number; Unit of Measure: percentage of participants
	86.0	73.8	86.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD, DMPA-SC
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Statistical non-inferiority was defined when the lower bound of the 95% 2-sided confidence interval for the difference between an elagolix dose and DMPA-SC in the response rate was no less than -20% at week 24 for both dysmenorrhea and non-menstrual pelvic pain.
Statistical Test of Hypothesis	P-Value	0.9630
	Comments	[Not Specified]
	Method	Pearson chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -13.4 to 12.7
	Estimation Comments	Difference in response rate = elogolix - DMPA-SC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID, DMPA-SC
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Statistical non-inferiority was defined when the lower bound of the 95% 2-sided confidence interval for the difference between an elagolix dose and DMPA-SC in the response rate was no less than -20% at week 24 for both dysmenorrhea and non-menstrual pelvic pain.
Statistical Test of Hypothesis	P-Value	0.1010
	Comments	[Not Specified]
	Method	Pearson chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-12.4
	Confidence Interval	(2-Sided) 95%; -26.7 to 1.8
	Estimation Comments	Difference in response rate = elogolix - DMPA-SC

7. Secondary Outcome

Title	Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS at Week 24
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The non-menstrual pelvic pain score was based on participant's response to the question "Have you had pelvic pain during the last 28 days?" Participants were classified as responders for non-menstrual pelvic pain if they reported a 1 point or greater reduction (improvement) from baseline.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary visual analog scale (VAS) values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data.

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed	57	65	51
Measure Type: Number; Unit of Measure: percentage of participants
	86.0	76.9	76.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD, DMPA-SC
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Statistical non-inferiority was defined when the lower bound of the 95% 2-sided confidence interval for the difference between an elagolix dose and DMPA-SC in the response rate was no less than -20% at week 24 for both dysmenorrhea and non-menstrual pelvic pain.
Statistical Test of Hypothesis	P-Value	0.2048
	Comments	[Not Specified]
	Method	Pearson chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; -5.2 to 24.2
	Estimation Comments	Difference in response rates = elagolix - DMPA-SC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID, DMPA-SC
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Statistical non-inferiority was defined when the lower bound of the 95% 2-sided confidence interval for the difference between an elagolix dose and DMPA-SC in the response rate was no less than -20% at week 24 for both dysmenorrhea and non-menstrual pelvic pain.
Statistical Test of Hypothesis	P-Value	0.9544
	Comments	[Not Specified]
	Method	Pearson chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -15.1 to 16.0
	Estimation Comments	Difference in response rates = elagolix - DMPA-SC

8. Secondary Outcome

Title	Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The dysmenorrhea score was based on the participant's response to the question "Have you had painful menstruation during the last 28 days?". Participants were classified as responders for dysmenorrhea if they reported a 1 point or greater reduction (improvement) from baseline.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Measure Type: Number; Unit of Measure: percentage of participants
Week 4	Number Analyzed	81 participants	83 participants	83 participants
		75.3	80.7	74.7
Week 8	Number Analyzed	75 participants	75 participants	73 participants
		84.0	84.0	79.5
Week 12	Number Analyzed	71 participants	73 participants	67 participants
		73.2	82.2	82.1
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		87.5	82.6	91.2
Week 20	Number Analyzed	60 participants	68 participants	54 participants
		81.7	76.5	83.3
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		86.0	73.8	86.3
Week 28	Number Analyzed	48 participants	61 participants	45 participants
		70.8	57.4	93.3
Week 36	Number Analyzed	40 participants	56 participants	41 participants
		52.5	44.6	80.5
Week 48	Number Analyzed	33 participants	55 participants	39 participants
		63.6	58.2	66.7

9. Secondary Outcome

Title	Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The non-menstrual pelvic pain score was based on participant's response to the question "Have you had pelvic pain during the last 28 days?" Participants were classified as responders for non-menstrual pelvic pain if they reported a 1 point or greater reduction (improvement) from baseline.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Measure Type: Number; Unit of Measure: percentage of participants
Week 4	Number Analyzed	81 participants	83 participants	83 participants
		74.1	56.6	68.7
Week 8	Number Analyzed	75 participants	75 participants	73 participants
		82.7	76.0	82.2
Week 12	Number Analyzed	71 participants	73 participants	67 participants
		74.6	82.2	71.6
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		82.8	78.3	70.2
Week 20	Number Analyzed	60 participants	68 participants	54 participants
		81.7	80.9	75.9
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		86.0	76.9	76.5
Week 28	Number Analyzed	48 participants	61 participants	45 participants
		66.7	60.7	73.3
Week 36	Number Analyzed	40 participants	56 participants	41 participants
		67.5	60.7	68.3
Week 48	Number Analyzed	33 participants	55 participants	39 participants
		66.7	56.4	71.8

10. Secondary Outcome

Title	Change From Baseline in Total CPSSS During the Treatment Period
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain scores are based on the participant's assessment, pelvic tenderness and induration were assessed by the investigator based on findings associated with a pelvic examination. The total CPSSS has a maximum possible value of 15 (total score range: 0 to 15, where a lower score indicates less signs and symptoms of endometriosis or better functioning). Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	83 participants	81 participants
		-3.9 (0.29)	-3.7 (0.29)	-3.8 (0.29)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-4.9 (0.30)	-4.8 (0.30)	-4.5 (0.30)
Week 12	Number Analyzed	70 participants	72 participants	67 participants
		-4.6 (0.31)	-5.1 (0.30)	-4.2 (0.31)
Week 16	Number Analyzed	64 participants	69 participants	56 participants
		-5.5 (0.32)	-5.4 (0.31)	-4.6 (0.33)
Week 20	Number Analyzed	60 participants	68 participants	54 participants
		-5.1 (0.33)	-5.3 (0.31)	-4.8 (0.34)
Week 24	Number Analyzed	57 participants	64 participants	50 participants
		-5.5 (0.34)	-5.2 (0.32)	-5.3 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in total CPSSS at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-5.5
	Confidence Interval	(2-Sided) 95%; -6.2 to -4.8
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in total CPSSS at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-5.2
	Confidence Interval	(2-Sided) 95%; -5.8 to -4.5
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in total CPSSS at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-5.3
	Confidence Interval	(2-Sided) 95%; -6.0 to -4.6
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain scores are based on the participant's assessment, pelvic tenderness and induration were assessed by the investigator based on findings associated with a pelvic examination. The total CPSSS excluding dyspareunia has a maximum possible value of 12 (total score range: 0 to 12, where a lower score indicates less signs and symptoms of endometriosis or better functioning). Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	83 participants	81 participants
		-3.4 (0.25)	-3.4 (0.25)	-3.3 (0.25)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-4.1 (0.26)	-4.2 (0.26)	-3.8 (0.26)
Week 12	Number Analyzed	70 participants	72 participants	67 participants
		-3.8 (0.26)	-4.4 (0.26)	-3.7 (0.27)
Week 16	Number Analyzed	64 participants	69 participants	56 participants
		-4.6 (0.27)	-4.6 (0.27)	-3.9 (0.29)
Week 20	Number Analyzed	60 participants	68 participants	54 participants
		-4.4 (0.28)	-4.4 (0.27)	-4.1 (0.30)
Week 24	Number Analyzed	57 participants	64 participants	50 participants
		-4.6 (0.29)	-4.4 (0.28)	-4.5 (0.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in total CPSSS excluding dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-4.6
	Confidence Interval	(2-Sided) 95%; -5.1 to -4.0
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in total CPSSS excluding dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -5.0 to -3.9
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in total CPSSS excluding dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -5.1 to -3.9
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The dysmenorrhea score was based on the participant's response to the question "Have you had painful menstruation during the last 28 days?". Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	83 participants	83 participants
		-1.4 (0.11)	-1.5 (0.11)	-1.3 (0.11)
Week 8	Number Analyzed	75 participants	75 participants	73 participants
		-1.6 (0.11)	-1.7 (0.11)	-1.5 (0.12)
Week 12	Number Analyzed	71 participants	73 participants	67 participants
		-1.3 (0.12)	-1.7 (0.12)	-1.5 (0.12)
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		-1.6 (0.12)	-1.8 (0.12)	-1.8 (0.13)
Week 20	Number Analyzed	60 participants	68 participants	54 participants
		-1.4 (0.13)	-1.5 (0.12)	-1.4 (0.13)
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		-1.5 (0.13)	-1.4 (0.12)	-1.7 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in dysmenorrhea at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -1.7 to -1.2
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in dysmenorrhea at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -1.6 to -1.2
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in dysmenorrhea at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -1.9 to -1.4
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The dyspareunia score was based on the participant's response to the question "Have you had painful intercourse during the last 28 days?" Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	62 participants	48 participants	59 participants
		-0.6 (0.11)	-0.4 (0.13)	-0.5 (0.11)
Week 8	Number Analyzed	53 participants	47 participants	51 participants
		-0.9 (0.12)	-0.7 (0.13)	-0.8 (0.12)
Week 12	Number Analyzed	51 participants	46 participants	49 participants
		-1.0 (0.12)	-0.8 (0.13)	-0.6 (0.12)
Week 16	Number Analyzed	45 participants	42 participants	35 participants
		-1.2 (0.13)	-1.0 (0.13)	-0.8 (0.14)
Week 20	Number Analyzed	41 participants	38 participants	33 participants
		-0.9 (0.13)	-1.0 (0.14)	-0.8 (0.14)
Week 24	Number Analyzed	39 participants	38 participants	30 participants
		-1.2 (0.13)	-1.0 (0.14)	-0.8 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.9
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 2%; -1.2 to -0.7
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.5
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). The non-menstrual pelvic pain score was based on participant's response to the question "Have you had pelvic pain during the last 28 days?". Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	83 participants	83 participants
		-0.9 (0.09)	-0.8 (0.09)	-0.8 (0.09)
Week 8	Number Analyzed	75 participants	75 participants	73 participants
		-1.1 (0.09)	-1.1 (0.09)	-1.1 (0.09)
Week 12	Number Analyzed	71 participants	73 participants	67 participants
		-1.0 (0.09)	-1.1 (0.09)	-0.9 (0.10)
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		-1.2 (0.10)	-1.2 (0.09)	-0.9 (0.10)
Week 20	Number Analyzed	60 participants	68 participants	54 participants
		-1.1 (0.10)	-1.3 (0.10)	-1.0 (0.11)
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		-1.2 (0.10)	-1.2 (0.10)	-1.1 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in non-menstrual pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -1.4 to -1.0
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in non-menstrual pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -1.4 to -1.0
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in non-menstrual pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.3 to -0.8
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Pelvic tenderness was assessed by the investigator based on findings associated with a pelvic examination. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	83 participants	81 participants
		-0.6 (0.08)	-0.7 (0.08)	-0.7 (0.08)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-0.8 (0.09)	-0.8 (0.08)	-0.7 (0.09)
Week 12	Number Analyzed	70 participants	72 participants	67 participants
		-0.8 (0.09)	-0.9 (0.09)	-0.7 (0.09)
Week 16	Number Analyzed	64 participants	69 participants	56 participants
		-1.0 (0.09)	-0.9 (0.09)	-0.6 (0.09)
Week 20	Number Analyzed	60 participants	68 participants	54 participants
		-1.0 (0.09)	-0.8 (0.09)	-0.9 (0.10)
Week 24	Number Analyzed	57 participants	64 participants	50 participants
		-1.0 (0.09)	-1.0 (0.09)	-0.9 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in pelvic tenderness at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.8
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in pelvic tenderness at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.8
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in pelvic tenderness at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.7
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period
Description	The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Pelvic induration was assessed by the investigator based on findings associated with a pelvic examination. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	83 participants	81 participants
		-0.4 (0.08)	-0.5 (0.08)	-0.5 (0.08)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-0.7 (0.08)	-0.6 (0.08)	-0.6 (0.08)
Week 12	Number Analyzed	70 participants	72 participants	67 participants
		-0.7 (0.08)	-0.8 (0.08)	-0.6 (0.08)
Week 16	Number Analyzed	64 participants	69 participants	56 participants
		-0.9 (0.09)	-0.8 (0.08)	-0.7 (0.09)
Week 20	Number Analyzed	60 participants	68 participants	54 participants
		-0.9 (0.09)	-0.8 (0.08)	-0.8 (0.09)
Week 24	Number Analyzed	57 participants	64 participants	50 participants
		-0.9 (0.09)	-0.9 (0.09)	-0.8 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in pelvic induration at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.0 to -0.7
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in pelvic induration at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.7
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in pelvic induration at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.6
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain
Description	The VAS for pelvic pain was used as an assessment of pain intensity. The VAS was a horizontal line on which the left extreme was labeled "no pain" and the right extreme was labeled "worst pain ever felt" scored on a scale from of 0 (no pain) to 100 (worst pain ever felt). Participants indicated the worst level of pain felt over a 24-hour period by ''ticking'' the horizontal line on their e-Diary at approximately the same time each day. Monthly peak VAS for pelvic pain was defined as the maximum VAS pain score reported for an individual participant from the previous visit to the day of the current scheduled visit. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	83 participants	84 participants	82 participants
		-18.2 (2.97)	-14.4 (2.96)	-15.4 (2.98)
Week 8	Number Analyzed	76 participants	78 participants	74 participants
		-26.3 (3.06)	-28.1 (3.02)	-27.1 (3.08)
Week 12	Number Analyzed	70 participants	73 participants	66 participants
		-31.3 (3.14)	-32.7 (3.09)	-24.9 (3.20)
Week 16	Number Analyzed	65 participants	67 participants	58 participants
		-32.1 (3.24)	-37.8 (3.19)	-30.8 (3.38)
Week 20	Number Analyzed	58 participants	66 participants	54 participants
		-29.0 (3.40)	-37.9 (3.23)	-31.0 (3.51)
Week 24	Number Analyzed	55 participants	63 participants	50 participants
		-32.3 (3.51)	-32.9 (3.31)	-35.8 (3.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in peak VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-32.3
	Confidence Interval	(2-Sided) 95%; -39.2 to -25.4
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in peak VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-32.9
	Confidence Interval	(2-Sided) 95%; -39.4 to -26.4
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in peak VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-35.8
	Confidence Interval	(2-Sided) 95%; -43.0 to -28.6
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain
Description	The VAS for pelvic pain was used as an assessment of pain intensity. The VAS was a horizontal line on which the left extreme was labeled "no pain" and the right extreme was labeled "worst pain ever felt" scored on a scale from of 0 (no pain) to 100 (worst pain ever felt). Participants indicated the worst level of pain felt over a 24-hour period by ''ticking'' the horizontal line on their e-Diary at approximately the same time each day. Monthly mean VAS for pelvic pain defined as the average of all VAS pain scores reported for an individual participant from the previous visit to the day of the current scheduled visit. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Week 4	Number Analyzed	83 participants	84 participants	82 participants
		-10.2 (1.59)	-11.7 (1.58)	-10.2 (1.59)
Week 8	Number Analyzed	76 participants	78 participants	74 participants
		-14.0 (2.09)	-17.8 (2.06)	-15.9 (2.10)
Week 12	Number Analyzed	70 participants	73 participants	66 participants
		-17.7 (2.24)	-23.4 (2.19)	-15.5 (2.27)
Week 16	Number Analyzed	65 participants	67 participants	58 participants
		-17.8 (2.51)	-23.6 (2.45)	-17.3 (2.57)
Week 20	Number Analyzed	58 participants	66 participants	54 participants
		-16.6 (2.53)	-24.1 (2.43)	-17.1 (2.59)
Week 24	Number Analyzed	55 participants	63 participants	50 participants
		-18.2 (2.57)	-23.4 (2.47)	-17.9 (2.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in monthly mean VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-18.2
	Confidence Interval	(2-Sided) 95%; -23.3 to -13.1
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in monthly mean VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-23.4
	Confidence Interval	(2-Sided) 95%; -28.3 to -18.5
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in peak VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-17.9
	Confidence Interval	(2-Sided) 95%; -23.1 to -12.7
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	82 participants	83 participants
		-20.7 (2.4)	-22.9 (2.6)	-18.7 (2.5)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-22.0 (3.1)	-30.0 (2.5)	-24.3 (2.6)
Week 12	Number Analyzed	71 participants	73 participants	67 participants
		-23.2 (3.1)	-28.4 (3.2)	-25.4 (3.4)
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		-30.9 (3.1)	-31.9 (2.8)	-29.8 (3.7)
Week 20	Number Analyzed	60 participants	68 participants	53 participants
		-26.3 (3.8)	-29.8 (2.8)	-28.3 (3.6)
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		-28.9 (3.2)	-28.5 (3.2)	-30.9 (4.1)

20. Secondary Outcome

Title	Change From Baseline in EHP-5 Control and Powerlessness Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	82 participants	83 participants
		-19.8 (2.9)	-24.7 (3.0)	-22.9 (2.6)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-27.7 (3.1)	-33.0 (3.5)	-31.2 (3.5)
Week 12	Number Analyzed	71 participants	73 participants	67 participants
		-30.6 (3.3)	-31.2 (3.8)	-26.1 (4.0)
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		-34.4 (3.7)	-33.3 (3.8)	-31.1 (4.3)
Week 20	Number Analyzed	60 participants	68 participants	53 participants
		-32.9 (3.8)	-33.1 (4.2)	-34.9 (4.4)
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		-37.3 (3.8)	-33.1 (3.8)	-35.8 (5.0)

21. Secondary Outcome

Title	Change From Baseline in EHP-5 Emotional Well-being Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	82 participants	83 participants
		-12.7 (2.5)	-10.4 (2.7)	-5.1 (2.8)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-20.6 (2.7)	-16.0 (3.1)	-13.4 (2.9)
Week 12	Number Analyzed	71 participants	73 participants	67 participants
		-18.0 (3.0)	-21.9 (3.2)	-14.6 (2.6)
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		-21.1 (3.3)	-20.7 (3.6)	-14.9 (3.7)
Week 20	Number Analyzed	60 participants	68 participants	53 participants
		-20.8 (3.7)	-22.8 (3.1)	-18.4 (3.8)
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		-24.1 (3.6)	-23.8 (3.4)	-25.5 (4.2)

22. Secondary Outcome

Title	Change From Baseline in EHP-5 Social Support Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	82 participants	83 participants
		-25.3 (3.0)	-26.5 (3.4)	-19.6 (2.9)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-31.4 (3.5)	-33.7 (3.9)	-29.8 (3.4)
Week 12	Number Analyzed	70 participants	73 participants	67 participants
		-36.8 (3.7)	-34.6 (4.4)	-28.4 (3.6)
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		-42.2 (4.0)	-37.0 (4.3)	-32.0 (3.7)
Week 20	Number Analyzed	60 participants	68 participants	53 participants
		-42.1 (4.2)	-39.0 (4.4)	-34.9 (3.9)
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		-43.4 (4.1)	-40.0 (4.4)	-32.8 (5.1)

23. Secondary Outcome

Title	Change From Baseline in EHP-5 Self Image Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	81 participants	82 participants	83 participants
		-11.1 (3.3)	-20.1 (2.9)	-11.1 (3.5)
Week 8	Number Analyzed	74 participants	75 participants	73 participants
		-19.6 (3.3)	-22.7 (3.3)	-17.5 (3.8)
Week 12	Number Analyzed	71 participants	73 participants	67 participants
		-21.1 (4.0)	-22.6 (3.2)	-18.3 (4.1)
Week 16	Number Analyzed	64 participants	69 participants	57 participants
		-20.3 (3.6)	-25.7 (3.1)	-18.9 (3.9)
Week 20	Number Analyzed	60 participants	68 participants	53 participants
		-20.8 (4.3)	-26.1 (3.4)	-19.3 (4.4)
Week 24	Number Analyzed	57 participants	65 participants	51 participants
		-23.7 (4.1)	-26.9 (3.8)	-24.5 (4.9)

24. Secondary Outcome

Title	Change From Baseline in EHP-5 Work Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	73 participants	73 participants	75 participants
		-20.5 (3.2)	-20.9 (2.8)	-21.0 (2.6)
Week 8	Number Analyzed	66 participants	66 participants	64 participants
		-21.2 (3.5)	-25.8 (3.1)	-25.8 (3.3)
Week 12	Number Analyzed	62 participants	66 participants	58 participants
		-21.8 (3.8)	-24.2 (3.3)	-25.4 (3.7)
Week 16	Number Analyzed	58 participants	63 participants	47 participants
		-24.6 (3.9)	-26.6 (3.2)	-26.6 (4.0)
Week 20	Number Analyzed	54 participants	61 participants	45 participants
		-24.1 (4.2)	-27.5 (3.1)	-29.4 (4.1)
Week 24	Number Analyzed	51 participants	58 participants	44 participants
		-24.0 (4.0)	-26.7 (3.1)	-27.8 (4.2)

25. Secondary Outcome

Title	Change From Baseline in EHP-5 Relationship With Children Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	42 participants	37 participants	45 participants
		-16.1 (4.4)	-18.9 (3.8)	-16.1 (3.9)
Week 8	Number Analyzed	39 participants	36 participants	39 participants
		-19.9 (4.5)	-20.8 (3.8)	-24.4 (3.9)
Week 12	Number Analyzed	37 participants	35 participants	35 participants
		-23.0 (4.8)	-20.7 (4.2)	-28.6 (4.8)
Week 16	Number Analyzed	31 participants	32 participants	30 participants
		-24.2 (4.7)	-26.6 (4.2)	-25.8 (5.0)
Week 20	Number Analyzed	27 participants	28 participants	28 participants
		-27.8 (4.3)	-25.0 (4.1)	-28.6 (5.7)
Week 24	Number Analyzed	26 participants	29 participants	26 participants
		-29.8 (4.6)	-23.3 (4.3)	-31.7 (6.0)

26. Secondary Outcome

Title	Change From Baseline in EHP-5 Intercourse Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	71 participants	65 participants	69 participants
		-17.3 (3.3)	-18.5 (3.6)	-17.4 (3.3)
Week 8	Number Analyzed	62 participants	57 participants	61 participants
		-25.8 (3.5)	-27.2 (3.8)	-20.5 (4.3)
Week 12	Number Analyzed	61 participants	56 participants	55 participants
		-29.1 (3.7)	-29.5 (4.0)	-20.5 (4.4)
Week 16	Number Analyzed	52 participants	54 participants	43 participants
		-31.7 (4.3)	-29.2 (3.8)	-23.3 (5.1)
Week 20	Number Analyzed	48 participants	52 participants	41 participants
		-30.7 (4.4)	-31.7 (4.2)	-25.0 (5.2)
Week 24	Number Analyzed	46 participants	45 participants	39 participants
		-35.3 (4.4)	-33.9 (4.4)	-29.5 (5.4)

27. Secondary Outcome

Title	Change From Baseline in EHP-5 Medical Profession Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	70 participants	69 participants	71 participants
		-13.2 (3.4)	-9.1 (2.6)	-12.0 (2.6)
Week 8	Number Analyzed	62 participants	63 participants	65 participants
		-15.3 (3.0)	-14.7 (3.2)	-13.5 (3.2)
Week 12	Number Analyzed	60 participants	60 participants	60 participants
		-16.7 (3.4)	-14.2 (3.7)	-15.0 (3.2)
Week 16	Number Analyzed	53 participants	59 participants	49 participants
		-18.9 (3.6)	-14.4 (3.4)	-17.9 (3.5)
Week 20	Number Analyzed	48 participants	60 participants	48 participants
		-18.2 (3.8)	-14.6 (3.2)	-15.6 (3.8)
Week 24	Number Analyzed	48 participants	57 participants	47 participants
		-18.8 (3.5)	-14.0 (3.5)	-16.0 (4.1)

28. Secondary Outcome

Title	Change From Baseline in EHP-5 Treatment Dimension
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; A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat) with available data at each time point.

Arm/Group Title		Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:		Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed		84	84	83
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	52 participants	53 participants	55 participants
		-27.4 (5.1)	-30.2 (4.5)	-26.8 (4.4)
Week 8	Number Analyzed	48 participants	50 participants	47 participants
		-32.8 (6.3)	-37.0 (4.8)	-29.8 (4.8)
Week 12	Number Analyzed	45 participants	45 participants	42 participants
		-35.0 (6.0)	-37.2 (5.5)	-28.0 (5.3)
Week 16	Number Analyzed	38 participants	47 participants	35 participants
		-36.8 (6.9)	-38.3 (4.6)	-28.6 (6.4)
Week 20	Number Analyzed	35 participants	46 participants	33 participants
		-35.7 (6.6)	-34.8 (5.2)	-35.6 (6.3)
Week 24	Number Analyzed	33 participants	42 participants	32 participants
		-35.6 (7.1)	-39.3 (5.0)	-28.9 (7.3)

29. Secondary Outcome

Title	Percentage of Participants Using Analgesics During the Treatment Phase
Description	Analgesic use was collected as part of concomitant medications on a case report form that was administered at each scheduled visit.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one oral dose of study drug, an initial subcutaneous injection, and either reported at least 7 e-diary VAS values or provided an assessment of either dysmenorrhea or non-menstrual pelvic pain at week 4 or later during the treatment phase (intent-to-treat).

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description:	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Overall Number of Participants Analyzed	84	84	83
Measure Type: Number; Unit of Measure: percentage of participants
Antiinflammatory/Antirheumatics, Non-Steroids	65.5	64.3	68.7
Opioids	23.8	25.0	33.7
Other Analgesics and Antipyretics	45.2	46.4	34.9

Adverse Events

Time Frame	From first dose of study drug through 24 weeks after last dose (48 weeks)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Elagolix 150 mg QD		Elagolix 75 mg BID		DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.		Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.		Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
All-Cause Mortality
	Elagolix 150 mg QD		Elagolix 75 mg BID		DMPA-SC
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/84 (0.00%)		0/84 (0.00%)		0/84 (0.00%)
Serious Adverse Events
	Elagolix 150 mg QD		Elagolix 75 mg BID		DMPA-SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/84 (3.57%)		3/84 (3.57%)		6/84 (7.14%)
Gastrointestinal disorders
FOOD POISONING † 1	0/84 (0.00%)	0	0/84 (0.00%)	0	1/84 (1.19%)	1
General disorders
CHEST PAIN † 1	0/84 (0.00%)	0	0/84 (0.00%)	0	1/84 (1.19%)	1
Infections and infestations
APPENDICITIS † 1	0/84 (0.00%)	0	0/84 (0.00%)	0	1/84 (1.19%)	1
PNEUMONIA † 1	0/84 (0.00%)	0	1/84 (1.19%)	1	0/84 (0.00%)	0
Metabolism and nutrition disorders
DEHYDRATION † 1	1/84 (1.19%)	1	0/84 (0.00%)	0	0/84 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OVARIAN DYSGERMINOMA STAGE I † 1	1/84 (1.19%)	1	0/84 (0.00%)	0	0/84 (0.00%)	0
Nervous system disorders
MIGRAINE † 1	0/84 (0.00%)	0	1/84 (1.19%)	1	0/84 (0.00%)	0
Psychiatric disorders
DEPRESSION SUICIDAL † 1	0/84 (0.00%)	0	1/84 (1.19%)	1	0/84 (0.00%)	0
Reproductive system and breast disorders
PELVIC CONGESTION † 1	0/84 (0.00%)	0	0/84 (0.00%)	0	1/84 (1.19%)	1
PELVIC PAIN † 1	1/84 (1.19%)	1	0/84 (0.00%)	0	1/84 (1.19%)	1
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX † 1	0/84 (0.00%)	0	0/84 (0.00%)	0	1/84 (1.19%)	1
1 Term from vocabulary, medDRA 6.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Elagolix 150 mg QD		Elagolix 75 mg BID		DMPA-SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/84 (75.00%)		59/84 (70.24%)		63/84 (75.00%)
Gastrointestinal disorders
ABDOMINAL DISTENSION † 1	2/84 (2.38%)	2	0/84 (0.00%)	0	6/84 (7.14%)	7
DIARRHOEA † 1	4/84 (4.76%)	4	9/84 (10.71%)	10	8/84 (9.52%)	10
DYSPEPSIA † 1	1/84 (1.19%)	1	5/84 (5.95%)	7	3/84 (3.57%)	3
NAUSEA † 1	16/84 (19.05%)	21	13/84 (15.48%)	16	13/84 (15.48%)	20
General disorders
FATIGUE † 1	5/84 (5.95%)	5	3/84 (3.57%)	3	6/84 (7.14%)	6
Infections and infestations
INFLUENZA † 1	7/84 (8.33%)	7	5/84 (5.95%)	5	2/84 (2.38%)	2
NASOPHARYNGITIS † 1	9/84 (10.71%)	9	18/84 (21.43%)	22	9/84 (10.71%)	11
SINUSITIS † 1	7/84 (8.33%)	8	7/84 (8.33%)	12	6/84 (7.14%)	6
UPPER RESPIRATORY TRACT INFECTION † 1	8/84 (9.52%)	10	10/84 (11.90%)	14	10/84 (11.90%)	10
URINARY TRACT INFECTION † 1	5/84 (5.95%)	6	8/84 (9.52%)	10	5/84 (5.95%)	5
VAGINAL MYCOSIS † 1	5/84 (5.95%)	6	4/84 (4.76%)	5	3/84 (3.57%)	3
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	4/84 (4.76%)	10	9/84 (10.71%)	13	2/84 (2.38%)	2
BACK PAIN † 1	6/84 (7.14%)	7	10/84 (11.90%)	11	4/84 (4.76%)	4
Nervous system disorders
DIZZINESS † 1	3/84 (3.57%)	4	6/84 (7.14%)	8	8/84 (9.52%)	9
HEADACHE † 1	22/84 (26.19%)	48	23/84 (27.38%)	66	15/84 (17.86%)	64
MIGRAINE † 1	4/84 (4.76%)	8	3/84 (3.57%)	3	5/84 (5.95%)	6
Psychiatric disorders
ANXIETY † 1	6/84 (7.14%)	6	4/84 (4.76%)	4	4/84 (4.76%)	4
DEPRESSION † 1	3/84 (3.57%)	3	6/84 (7.14%)	6	4/84 (4.76%)	4
INSOMNIA † 1	4/84 (4.76%)	4	7/84 (8.33%)	11	4/84 (4.76%)	4
MOOD SWINGS † 1	7/84 (8.33%)	8	6/84 (7.14%)	6	10/84 (11.90%)	10
Reproductive system and breast disorders
OVARIAN CYST † 1	5/84 (5.95%)	5	0/84 (0.00%)	0	1/84 (1.19%)	1
Respiratory, thoracic and mediastinal disorders
COUGH † 1	2/84 (2.38%)	2	6/84 (7.14%)	7	3/84 (3.57%)	3
NASAL CONGESTION † 1	4/84 (4.76%)	5	6/84 (7.14%)	6	3/84 (3.57%)	3
PHARYNGOLARYNGEAL PAIN † 1	7/84 (8.33%)	9	7/84 (8.33%)	8	3/84 (3.57%)	3
SINUS CONGESTION † 1	3/84 (3.57%)	3	5/84 (5.95%)	6	5/84 (5.95%)	5
Skin and subcutaneous tissue disorders
ACNE † 1	7/84 (8.33%)	7	2/84 (2.38%)	2	7/84 (8.33%)	7
1 Term from vocabulary, medDRA 6.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT00437658
• Other Study ID Numbers: NBI-56418-0603
• First Submitted: February 16, 2007
• First Posted: February 21, 2007
• Results First Submitted: August 9, 2018
• Results First Posted: October 12, 2018
• Last Update Posted: October 12, 2018