Trial Outcomes & Findings for Elagolix Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis (NCT NCT00437658)

NCT ID: NCT00437658

Last Updated: 2018-10-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 252 participants
• Primary outcome timeframe: Baseline and week 24
• Results posted on: 2018-10-12

Participant Flow

Participants were randomized at 58 centers in the United States.

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.

Participant milestones

Measure	Elagolix 150 mg QD 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.	Elagolix 75 mg BID 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.	DMPA-SC 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.
Treatment Period (24 Weeks) STARTED	84	84	84
Treatment Period (24 Weeks) Received Study Drug	84	84	84
Treatment Period (24 Weeks) COMPLETED	56	62	51
Treatment Period (24 Weeks) NOT COMPLETED	28	22	33
Post-treatment Period (24 Weeks) STARTED	56	62	51
Post-treatment Period (24 Weeks) COMPLETED	32	54	37
Post-treatment Period (24 Weeks) NOT COMPLETED	24	8	14

Reasons for withdrawal

Measure	Elagolix 150 mg QD 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.	Elagolix 75 mg BID 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.	DMPA-SC 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.
Treatment Period (24 Weeks) Adverse Event	4	7	14
Treatment Period (24 Weeks) Non-compliance	1	1	4
Treatment Period (24 Weeks) Withdrawal by Subject	9	7	7
Treatment Period (24 Weeks) Lack of Efficacy	4	2	3
Treatment Period (24 Weeks) Lost to Follow-up	5	4	5
Treatment Period (24 Weeks) Sponsor/Investigator Decision	5	1	0
Post-treatment Period (24 Weeks) Adverse Event	1	0	1
Post-treatment Period (24 Weeks) Non-compliance	3	0	1
Post-treatment Period (24 Weeks) Withdrawal by Subject	12	6	8
Post-treatment Period (24 Weeks) Lack of Efficacy	0	2	2
Post-treatment Period (24 Weeks) Lost to Follow-up	5	0	1
Post-treatment Period (24 Weeks) Sponsor/Investigator Decision	3	0	1

Baseline Characteristics

Elagolix Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis

Baseline characteristics by cohort

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=84 Participants 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 n=252 Participants Total of all reporting groups
Age, Continuous	32.4 years STANDARD_DEVIATION 7.5 • n=5 Participants	31.4 years STANDARD_DEVIATION 6.1 • n=7 Participants	30.9 years STANDARD_DEVIATION 6.3 • n=5 Participants	31.6 years STANDARD_DEVIATION 6.7 • n=4 Participants
Sex: Female, Male Female	84 Participants n=5 Participants	84 Participants n=7 Participants	84 Participants n=5 Participants	252 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Black	6 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	26 Participants n=4 Participants
Race/Ethnicity, Customized White	68 Participants n=5 Participants	70 Participants n=7 Participants	65 Participants n=5 Participants	203 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	8 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native, Caucasian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black, Caucasian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian, Hispanic	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and week 24

Population: 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

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.

Outcome measures

Measure	Elagolix 150 mg QD n=55 Participants 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.	Elagolix 75 mg BID n=62 Participants 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.	DMPA-SC n=50 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24	-0.11 percent change Interval -0.7 to 0.48	-1.29 percent change Interval -1.85 to -0.74	-0.99 percent change Interval -1.61 to -0.37

PRIMARY outcome

Timeframe: Baseline and week 24

Population: 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

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.

Outcome measures

Measure	Elagolix 150 mg QD n=56 Participants 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.	Elagolix 75 mg BID n=64 Participants 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.	DMPA-SC n=51 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24	-0.47 percent change Interval -0.96 to 0.02	-1.02 percent change Interval -1.48 to -0.56	-1.29 percent change Interval -1.8 to -0.77

SECONDARY outcome

Timeframe: Baseline and weeks 12 and 48

Population: 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

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=84 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Spine at Weeks 12 and 48 Week 12	-0.39 percent change Interval -0.8 to 0.02	-1.05 percent change Interval -1.46 to -0.64	-0.57 percent change Interval -0.98 to -0.15
Percent Change From Baseline in Bone Mineral Density of the Spine at Weeks 12 and 48 Week 48	0.20 percent change Interval -0.57 to 0.96	-0.49 percent change Interval -1.09 to 0.1	-0.56 percent change Interval -1.27 to 0.15

SECONDARY outcome

Timeframe: Baseline and weeks 12 and 48

Population: 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

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=84 Participants 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.
Percent Change From Baseline in Bone Mineral Density of the Femur at Weeks 12 and 48 Week 12	-0.63 percent change Interval -1.02 to -0.24	-0.54 percent change Interval -0.92 to -0.17	-0.77 percent change Interval -1.16 to -0.39
Percent Change From Baseline in Bone Mineral Density of the Femur at Weeks 12 and 48 Week 48	-0.38 percent change Interval -1.1 to 0.33	-0.86 percent change Interval -1.41 to -0.32	-0.76 percent change Interval -1.42 to -0.1

SECONDARY outcome

Timeframe: Baseline and weeks 12, 24 and 48

Population: 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

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=84 Participants 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.
Change From Baseline in N-telopeptide at Weeks 12, 24 and 48 Week 24	0.23 nM bone collagen equivalents (BCE) Standard Error 0.50	-0.30 nM bone collagen equivalents (BCE) Standard Error 0.48	-0.24 nM bone collagen equivalents (BCE) Standard Error 0.54
Change From Baseline in N-telopeptide at Weeks 12, 24 and 48 Week 12	0.94 nM bone collagen equivalents (BCE) Standard Error 0.43	0.57 nM bone collagen equivalents (BCE) Standard Error 0.43	0.74 nM bone collagen equivalents (BCE) Standard Error 0.45
Change From Baseline in N-telopeptide at Weeks 12, 24 and 48 Week 48	-1.28 nM bone collagen equivalents (BCE) Standard Error 0.61	-1.53 nM bone collagen equivalents (BCE) Standard Error 0.48	-1.39 nM bone collagen equivalents (BCE) Standard Error 0.58

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=57 Participants 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.	Elagolix 75 mg BID n=65 Participants 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.	DMPA-SC n=51 Participants 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.
Percentage of Participants With a Response in the Dysmenorrhea Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) at Week 24	86.0 percentage of participants	73.8 percentage of participants	86.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=57 Participants 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.	Elagolix 75 mg BID n=65 Participants 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.	DMPA-SC n=51 Participants 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.
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS at Week 24	86.0 percentage of participants	76.9 percentage of participants	76.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 4	75.3 percentage of participants	80.7 percentage of participants	74.7 percentage of participants
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 8	84.0 percentage of participants	84.0 percentage of participants	79.5 percentage of participants
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 12	73.2 percentage of participants	82.2 percentage of participants	82.1 percentage of participants
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 16	87.5 percentage of participants	82.6 percentage of participants	91.2 percentage of participants
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 20	81.7 percentage of participants	76.5 percentage of participants	83.3 percentage of participants
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 24	86.0 percentage of participants	73.8 percentage of participants	86.3 percentage of participants
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 28	70.8 percentage of participants	57.4 percentage of participants	93.3 percentage of participants
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 36	52.5 percentage of participants	44.6 percentage of participants	80.5 percentage of participants
Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time Week 48	63.6 percentage of participants	58.2 percentage of participants	66.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 4	74.1 percentage of participants	56.6 percentage of participants	68.7 percentage of participants
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 8	82.7 percentage of participants	76.0 percentage of participants	82.2 percentage of participants
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 12	74.6 percentage of participants	82.2 percentage of participants	71.6 percentage of participants
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 16	82.8 percentage of participants	78.3 percentage of participants	70.2 percentage of participants
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 20	81.7 percentage of participants	80.9 percentage of participants	75.9 percentage of participants
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 24	86.0 percentage of participants	76.9 percentage of participants	76.5 percentage of participants
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 28	66.7 percentage of participants	60.7 percentage of participants	73.3 percentage of participants
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 36	67.5 percentage of participants	60.7 percentage of participants	68.3 percentage of participants
Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time Week 48	66.7 percentage of participants	56.4 percentage of participants	71.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in Total CPSSS During the Treatment Period Week 4	-3.9 units on a scale Standard Error 0.29	-3.7 units on a scale Standard Error 0.29	-3.8 units on a scale Standard Error 0.29
Change From Baseline in Total CPSSS During the Treatment Period Week 8	-4.9 units on a scale Standard Error 0.30	-4.8 units on a scale Standard Error 0.30	-4.5 units on a scale Standard Error 0.30
Change From Baseline in Total CPSSS During the Treatment Period Week 12	-4.6 units on a scale Standard Error 0.31	-5.1 units on a scale Standard Error 0.30	-4.2 units on a scale Standard Error 0.31
Change From Baseline in Total CPSSS During the Treatment Period Week 16	-5.5 units on a scale Standard Error 0.32	-5.4 units on a scale Standard Error 0.31	-4.6 units on a scale Standard Error 0.33
Change From Baseline in Total CPSSS During the Treatment Period Week 20	-5.1 units on a scale Standard Error 0.33	-5.3 units on a scale Standard Error 0.31	-4.8 units on a scale Standard Error 0.34
Change From Baseline in Total CPSSS During the Treatment Period Week 24	-5.5 units on a scale Standard Error 0.34	-5.2 units on a scale Standard Error 0.32	-5.3 units on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period Week 4	-3.4 units on a scale Standard Error 0.25	-3.4 units on a scale Standard Error 0.25	-3.3 units on a scale Standard Error 0.25
Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period Week 8	-4.1 units on a scale Standard Error 0.26	-4.2 units on a scale Standard Error 0.26	-3.8 units on a scale Standard Error 0.26
Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period Week 12	-3.8 units on a scale Standard Error 0.26	-4.4 units on a scale Standard Error 0.26	-3.7 units on a scale Standard Error 0.27
Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period Week 16	-4.6 units on a scale Standard Error 0.27	-4.6 units on a scale Standard Error 0.27	-3.9 units on a scale Standard Error 0.29
Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period Week 20	-4.4 units on a scale Standard Error 0.28	-4.4 units on a scale Standard Error 0.27	-4.1 units on a scale Standard Error 0.30
Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period Week 24	-4.6 units on a scale Standard Error 0.29	-4.4 units on a scale Standard Error 0.28	-4.5 units on a scale Standard Error 0.31

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period Week 4	-1.4 units on a scale Standard Error 0.11	-1.5 units on a scale Standard Error 0.11	-1.3 units on a scale Standard Error 0.11
Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period Week 8	-1.6 units on a scale Standard Error 0.11	-1.7 units on a scale Standard Error 0.11	-1.5 units on a scale Standard Error 0.12
Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period Week 12	-1.3 units on a scale Standard Error 0.12	-1.7 units on a scale Standard Error 0.12	-1.5 units on a scale Standard Error 0.12
Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period Week 16	-1.6 units on a scale Standard Error 0.12	-1.8 units on a scale Standard Error 0.12	-1.8 units on a scale Standard Error 0.13
Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period Week 20	-1.4 units on a scale Standard Error 0.13	-1.5 units on a scale Standard Error 0.12	-1.4 units on a scale Standard Error 0.13
Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period Week 24	-1.5 units on a scale Standard Error 0.13	-1.4 units on a scale Standard Error 0.12	-1.7 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period Week 4	-0.6 units on a scale Standard Error 0.11	-0.4 units on a scale Standard Error 0.13	-0.5 units on a scale Standard Error 0.11
Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period Week 8	-0.9 units on a scale Standard Error 0.12	-0.7 units on a scale Standard Error 0.13	-0.8 units on a scale Standard Error 0.12
Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period Week 12	-1.0 units on a scale Standard Error 0.12	-0.8 units on a scale Standard Error 0.13	-0.6 units on a scale Standard Error 0.12
Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period Week 16	-1.2 units on a scale Standard Error 0.13	-1.0 units on a scale Standard Error 0.13	-0.8 units on a scale Standard Error 0.14
Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period Week 20	-0.9 units on a scale Standard Error 0.13	-1.0 units on a scale Standard Error 0.14	-0.8 units on a scale Standard Error 0.14
Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period Week 24	-1.2 units on a scale Standard Error 0.13	-1.0 units on a scale Standard Error 0.14	-0.8 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period Week 4	-0.9 units on a scale Standard Error 0.09	-0.8 units on a scale Standard Error 0.09	-0.8 units on a scale Standard Error 0.09
Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period Week 8	-1.1 units on a scale Standard Error 0.09	-1.1 units on a scale Standard Error 0.09	-1.1 units on a scale Standard Error 0.09
Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period Week 12	-1.0 units on a scale Standard Error 0.09	-1.1 units on a scale Standard Error 0.09	-0.9 units on a scale Standard Error 0.10
Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period Week 16	-1.2 units on a scale Standard Error 0.10	-1.2 units on a scale Standard Error 0.09	-0.9 units on a scale Standard Error 0.10
Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period Week 20	-1.1 units on a scale Standard Error 0.10	-1.3 units on a scale Standard Error 0.10	-1.0 units on a scale Standard Error 0.11
Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period Week 24	-1.2 units on a scale Standard Error 0.10	-1.2 units on a scale Standard Error 0.10	-1.1 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period Week 4	-0.6 units on a scale Standard Error 0.08	-0.7 units on a scale Standard Error 0.08	-0.7 units on a scale Standard Error 0.08
Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period Week 8	-0.8 units on a scale Standard Error 0.09	-0.8 units on a scale Standard Error 0.08	-0.7 units on a scale Standard Error 0.09
Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period Week 12	-0.8 units on a scale Standard Error 0.09	-0.9 units on a scale Standard Error 0.09	-0.7 units on a scale Standard Error 0.09
Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period Week 16	-1.0 units on a scale Standard Error 0.09	-0.9 units on a scale Standard Error 0.09	-0.6 units on a scale Standard Error 0.09
Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period Week 20	-1.0 units on a scale Standard Error 0.09	-0.8 units on a scale Standard Error 0.09	-0.9 units on a scale Standard Error 0.10
Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period Week 24	-1.0 units on a scale Standard Error 0.09	-1.0 units on a scale Standard Error 0.09	-0.9 units on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period Week 4	-0.4 units on a scale Standard Error 0.08	-0.5 units on a scale Standard Error 0.08	-0.5 units on a scale Standard Error 0.08
Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period Week 8	-0.7 units on a scale Standard Error 0.08	-0.6 units on a scale Standard Error 0.08	-0.6 units on a scale Standard Error 0.08
Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period Week 12	-0.7 units on a scale Standard Error 0.08	-0.8 units on a scale Standard Error 0.08	-0.6 units on a scale Standard Error 0.08
Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period Week 16	-0.9 units on a scale Standard Error 0.09	-0.8 units on a scale Standard Error 0.08	-0.7 units on a scale Standard Error 0.09
Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period Week 20	-0.9 units on a scale Standard Error 0.09	-0.8 units on a scale Standard Error 0.08	-0.8 units on a scale Standard Error 0.09
Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period Week 24	-0.9 units on a scale Standard Error 0.09	-0.9 units on a scale Standard Error 0.09	-0.8 units on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain Week 4	-18.2 units on a scale Standard Error 2.97	-14.4 units on a scale Standard Error 2.96	-15.4 units on a scale Standard Error 2.98
Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain Week 8	-26.3 units on a scale Standard Error 3.06	-28.1 units on a scale Standard Error 3.02	-27.1 units on a scale Standard Error 3.08
Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain Week 12	-31.3 units on a scale Standard Error 3.14	-32.7 units on a scale Standard Error 3.09	-24.9 units on a scale Standard Error 3.20
Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain Week 16	-32.1 units on a scale Standard Error 3.24	-37.8 units on a scale Standard Error 3.19	-30.8 units on a scale Standard Error 3.38
Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain Week 20	-29.0 units on a scale Standard Error 3.40	-37.9 units on a scale Standard Error 3.23	-31.0 units on a scale Standard Error 3.51
Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain Week 24	-32.3 units on a scale Standard Error 3.51	-32.9 units on a scale Standard Error 3.31	-35.8 units on a scale Standard Error 3.65

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain Week 4	-10.2 units on a scale Standard Error 1.59	-11.7 units on a scale Standard Error 1.58	-10.2 units on a scale Standard Error 1.59
Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain Week 8	-14.0 units on a scale Standard Error 2.09	-17.8 units on a scale Standard Error 2.06	-15.9 units on a scale Standard Error 2.10
Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain Week 12	-17.7 units on a scale Standard Error 2.24	-23.4 units on a scale Standard Error 2.19	-15.5 units on a scale Standard Error 2.27
Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain Week 16	-17.8 units on a scale Standard Error 2.51	-23.6 units on a scale Standard Error 2.45	-17.3 units on a scale Standard Error 2.57
Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain Week 20	-16.6 units on a scale Standard Error 2.53	-24.1 units on a scale Standard Error 2.43	-17.1 units on a scale Standard Error 2.59
Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain Week 24	-18.2 units on a scale Standard Error 2.57	-23.4 units on a scale Standard Error 2.47	-17.9 units on a scale Standard Error 2.64

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension Week 4	-20.7 units on a scale Standard Deviation 2.4	-22.9 units on a scale Standard Deviation 2.6	-18.7 units on a scale Standard Deviation 2.5
Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension Week 8	-22.0 units on a scale Standard Deviation 3.1	-30.0 units on a scale Standard Deviation 2.5	-24.3 units on a scale Standard Deviation 2.6
Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension Week 12	-23.2 units on a scale Standard Deviation 3.1	-28.4 units on a scale Standard Deviation 3.2	-25.4 units on a scale Standard Deviation 3.4
Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension Week 16	-30.9 units on a scale Standard Deviation 3.1	-31.9 units on a scale Standard Deviation 2.8	-29.8 units on a scale Standard Deviation 3.7
Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension Week 20	-26.3 units on a scale Standard Deviation 3.8	-29.8 units on a scale Standard Deviation 2.8	-28.3 units on a scale Standard Deviation 3.6
Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension Week 24	-28.9 units on a scale Standard Deviation 3.2	-28.5 units on a scale Standard Deviation 3.2	-30.9 units on a scale Standard Deviation 4.1

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Control and Powerlessness Dimension Week 4	-19.8 units on a scale Standard Deviation 2.9	-24.7 units on a scale Standard Deviation 3.0	-22.9 units on a scale Standard Deviation 2.6
Change From Baseline in EHP-5 Control and Powerlessness Dimension Week 8	-27.7 units on a scale Standard Deviation 3.1	-33.0 units on a scale Standard Deviation 3.5	-31.2 units on a scale Standard Deviation 3.5
Change From Baseline in EHP-5 Control and Powerlessness Dimension Week 12	-30.6 units on a scale Standard Deviation 3.3	-31.2 units on a scale Standard Deviation 3.8	-26.1 units on a scale Standard Deviation 4.0
Change From Baseline in EHP-5 Control and Powerlessness Dimension Week 16	-34.4 units on a scale Standard Deviation 3.7	-33.3 units on a scale Standard Deviation 3.8	-31.1 units on a scale Standard Deviation 4.3
Change From Baseline in EHP-5 Control and Powerlessness Dimension Week 20	-32.9 units on a scale Standard Deviation 3.8	-33.1 units on a scale Standard Deviation 4.2	-34.9 units on a scale Standard Deviation 4.4
Change From Baseline in EHP-5 Control and Powerlessness Dimension Week 24	-37.3 units on a scale Standard Deviation 3.8	-33.1 units on a scale Standard Deviation 3.8	-35.8 units on a scale Standard Deviation 5.0

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Emotional Well-being Dimension Week 4	-12.7 units on a scale Standard Deviation 2.5	-10.4 units on a scale Standard Deviation 2.7	-5.1 units on a scale Standard Deviation 2.8
Change From Baseline in EHP-5 Emotional Well-being Dimension Week 8	-20.6 units on a scale Standard Deviation 2.7	-16.0 units on a scale Standard Deviation 3.1	-13.4 units on a scale Standard Deviation 2.9
Change From Baseline in EHP-5 Emotional Well-being Dimension Week 12	-18.0 units on a scale Standard Deviation 3.0	-21.9 units on a scale Standard Deviation 3.2	-14.6 units on a scale Standard Deviation 2.6
Change From Baseline in EHP-5 Emotional Well-being Dimension Week 16	-21.1 units on a scale Standard Deviation 3.3	-20.7 units on a scale Standard Deviation 3.6	-14.9 units on a scale Standard Deviation 3.7
Change From Baseline in EHP-5 Emotional Well-being Dimension Week 20	-20.8 units on a scale Standard Deviation 3.7	-22.8 units on a scale Standard Deviation 3.1	-18.4 units on a scale Standard Deviation 3.8
Change From Baseline in EHP-5 Emotional Well-being Dimension Week 24	-24.1 units on a scale Standard Deviation 3.6	-23.8 units on a scale Standard Deviation 3.4	-25.5 units on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Social Support Dimension Week 4	-25.3 units on a scale Standard Deviation 3.0	-26.5 units on a scale Standard Deviation 3.4	-19.6 units on a scale Standard Deviation 2.9
Change From Baseline in EHP-5 Social Support Dimension Week 8	-31.4 units on a scale Standard Deviation 3.5	-33.7 units on a scale Standard Deviation 3.9	-29.8 units on a scale Standard Deviation 3.4
Change From Baseline in EHP-5 Social Support Dimension Week 12	-36.8 units on a scale Standard Deviation 3.7	-34.6 units on a scale Standard Deviation 4.4	-28.4 units on a scale Standard Deviation 3.6
Change From Baseline in EHP-5 Social Support Dimension Week 16	-42.2 units on a scale Standard Deviation 4.0	-37.0 units on a scale Standard Deviation 4.3	-32.0 units on a scale Standard Deviation 3.7
Change From Baseline in EHP-5 Social Support Dimension Week 20	-42.1 units on a scale Standard Deviation 4.2	-39.0 units on a scale Standard Deviation 4.4	-34.9 units on a scale Standard Deviation 3.9
Change From Baseline in EHP-5 Social Support Dimension Week 24	-43.4 units on a scale Standard Deviation 4.1	-40.0 units on a scale Standard Deviation 4.4	-32.8 units on a scale Standard Deviation 5.1

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Self Image Dimension Week 4	-11.1 units on a scale Standard Deviation 3.3	-20.1 units on a scale Standard Deviation 2.9	-11.1 units on a scale Standard Deviation 3.5
Change From Baseline in EHP-5 Self Image Dimension Week 8	-19.6 units on a scale Standard Deviation 3.3	-22.7 units on a scale Standard Deviation 3.3	-17.5 units on a scale Standard Deviation 3.8
Change From Baseline in EHP-5 Self Image Dimension Week 12	-21.1 units on a scale Standard Deviation 4.0	-22.6 units on a scale Standard Deviation 3.2	-18.3 units on a scale Standard Deviation 4.1
Change From Baseline in EHP-5 Self Image Dimension Week 16	-20.3 units on a scale Standard Deviation 3.6	-25.7 units on a scale Standard Deviation 3.1	-18.9 units on a scale Standard Deviation 3.9
Change From Baseline in EHP-5 Self Image Dimension Week 20	-20.8 units on a scale Standard Deviation 4.3	-26.1 units on a scale Standard Deviation 3.4	-19.3 units on a scale Standard Deviation 4.4
Change From Baseline in EHP-5 Self Image Dimension Week 24	-23.7 units on a scale Standard Deviation 4.1	-26.9 units on a scale Standard Deviation 3.8	-24.5 units on a scale Standard Deviation 4.9

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Work Dimension Week 4	-20.5 units on a scale Standard Deviation 3.2	-20.9 units on a scale Standard Deviation 2.8	-21.0 units on a scale Standard Deviation 2.6
Change From Baseline in EHP-5 Work Dimension Week 8	-21.2 units on a scale Standard Deviation 3.5	-25.8 units on a scale Standard Deviation 3.1	-25.8 units on a scale Standard Deviation 3.3
Change From Baseline in EHP-5 Work Dimension Week 12	-21.8 units on a scale Standard Deviation 3.8	-24.2 units on a scale Standard Deviation 3.3	-25.4 units on a scale Standard Deviation 3.7
Change From Baseline in EHP-5 Work Dimension Week 16	-24.6 units on a scale Standard Deviation 3.9	-26.6 units on a scale Standard Deviation 3.2	-26.6 units on a scale Standard Deviation 4.0
Change From Baseline in EHP-5 Work Dimension Week 20	-24.1 units on a scale Standard Deviation 4.2	-27.5 units on a scale Standard Deviation 3.1	-29.4 units on a scale Standard Deviation 4.1
Change From Baseline in EHP-5 Work Dimension Week 24	-24.0 units on a scale Standard Deviation 4.0	-26.7 units on a scale Standard Deviation 3.1	-27.8 units on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Relationship With Children Dimension Week 4	-16.1 units on a scale Standard Deviation 4.4	-18.9 units on a scale Standard Deviation 3.8	-16.1 units on a scale Standard Deviation 3.9
Change From Baseline in EHP-5 Relationship With Children Dimension Week 8	-19.9 units on a scale Standard Deviation 4.5	-20.8 units on a scale Standard Deviation 3.8	-24.4 units on a scale Standard Deviation 3.9
Change From Baseline in EHP-5 Relationship With Children Dimension Week 12	-23.0 units on a scale Standard Deviation 4.8	-20.7 units on a scale Standard Deviation 4.2	-28.6 units on a scale Standard Deviation 4.8
Change From Baseline in EHP-5 Relationship With Children Dimension Week 16	-24.2 units on a scale Standard Deviation 4.7	-26.6 units on a scale Standard Deviation 4.2	-25.8 units on a scale Standard Deviation 5.0
Change From Baseline in EHP-5 Relationship With Children Dimension Week 20	-27.8 units on a scale Standard Deviation 4.3	-25.0 units on a scale Standard Deviation 4.1	-28.6 units on a scale Standard Deviation 5.7
Change From Baseline in EHP-5 Relationship With Children Dimension Week 24	-29.8 units on a scale Standard Deviation 4.6	-23.3 units on a scale Standard Deviation 4.3	-31.7 units on a scale Standard Deviation 6.0

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Intercourse Dimension Week 4	-17.3 units on a scale Standard Deviation 3.3	-18.5 units on a scale Standard Deviation 3.6	-17.4 units on a scale Standard Deviation 3.3
Change From Baseline in EHP-5 Intercourse Dimension Week 8	-25.8 units on a scale Standard Deviation 3.5	-27.2 units on a scale Standard Deviation 3.8	-20.5 units on a scale Standard Deviation 4.3
Change From Baseline in EHP-5 Intercourse Dimension Week 12	-29.1 units on a scale Standard Deviation 3.7	-29.5 units on a scale Standard Deviation 4.0	-20.5 units on a scale Standard Deviation 4.4
Change From Baseline in EHP-5 Intercourse Dimension Week 16	-31.7 units on a scale Standard Deviation 4.3	-29.2 units on a scale Standard Deviation 3.8	-23.3 units on a scale Standard Deviation 5.1
Change From Baseline in EHP-5 Intercourse Dimension Week 20	-30.7 units on a scale Standard Deviation 4.4	-31.7 units on a scale Standard Deviation 4.2	-25.0 units on a scale Standard Deviation 5.2
Change From Baseline in EHP-5 Intercourse Dimension Week 24	-35.3 units on a scale Standard Deviation 4.4	-33.9 units on a scale Standard Deviation 4.4	-29.5 units on a scale Standard Deviation 5.4

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Medical Profession Dimension Week 4	-13.2 units on a scale Standard Deviation 3.4	-9.1 units on a scale Standard Deviation 2.6	-12.0 units on a scale Standard Deviation 2.6
Change From Baseline in EHP-5 Medical Profession Dimension Week 8	-15.3 units on a scale Standard Deviation 3.0	-14.7 units on a scale Standard Deviation 3.2	-13.5 units on a scale Standard Deviation 3.2
Change From Baseline in EHP-5 Medical Profession Dimension Week 12	-16.7 units on a scale Standard Deviation 3.4	-14.2 units on a scale Standard Deviation 3.7	-15.0 units on a scale Standard Deviation 3.2
Change From Baseline in EHP-5 Medical Profession Dimension Week 16	-18.9 units on a scale Standard Deviation 3.6	-14.4 units on a scale Standard Deviation 3.4	-17.9 units on a scale Standard Deviation 3.5
Change From Baseline in EHP-5 Medical Profession Dimension Week 20	-18.2 units on a scale Standard Deviation 3.8	-14.6 units on a scale Standard Deviation 3.2	-15.6 units on a scale Standard Deviation 3.8
Change From Baseline in EHP-5 Medical Profession Dimension Week 24	-18.8 units on a scale Standard Deviation 3.5	-14.0 units on a scale Standard Deviation 3.5	-16.0 units on a scale Standard Deviation 4.1

SECONDARY outcome

Timeframe: Baseline and weeks 4, 8, 12, 16, 20, and 24

Population: 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.

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.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Change From Baseline in EHP-5 Treatment Dimension Week 4	-27.4 units on a scale Standard Deviation 5.1	-30.2 units on a scale Standard Deviation 4.5	-26.8 units on a scale Standard Deviation 4.4
Change From Baseline in EHP-5 Treatment Dimension Week 8	-32.8 units on a scale Standard Deviation 6.3	-37.0 units on a scale Standard Deviation 4.8	-29.8 units on a scale Standard Deviation 4.8
Change From Baseline in EHP-5 Treatment Dimension Week 12	-35.0 units on a scale Standard Deviation 6.0	-37.2 units on a scale Standard Deviation 5.5	-28.0 units on a scale Standard Deviation 5.3
Change From Baseline in EHP-5 Treatment Dimension Week 16	-36.8 units on a scale Standard Deviation 6.9	-38.3 units on a scale Standard Deviation 4.6	-28.6 units on a scale Standard Deviation 6.4
Change From Baseline in EHP-5 Treatment Dimension Week 20	-35.7 units on a scale Standard Deviation 6.6	-34.8 units on a scale Standard Deviation 5.2	-35.6 units on a scale Standard Deviation 6.3
Change From Baseline in EHP-5 Treatment Dimension Week 24	-35.6 units on a scale Standard Deviation 7.1	-39.3 units on a scale Standard Deviation 5.0	-28.9 units on a scale Standard Deviation 7.3

SECONDARY outcome

Timeframe: 24 weeks

Population: 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).

Analgesic use was collected as part of concomitant medications on a case report form that was administered at each scheduled visit.

Outcome measures

Measure	Elagolix 150 mg QD n=84 Participants 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.	Elagolix 75 mg BID n=84 Participants 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.	DMPA-SC n=83 Participants 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.
Percentage of Participants Using Analgesics During the Treatment Phase Antiinflammatory/Antirheumatics, Non-Steroids	65.5 percentage of participants	64.3 percentage of participants	68.7 percentage of participants
Percentage of Participants Using Analgesics During the Treatment Phase Opioids	23.8 percentage of participants	25.0 percentage of participants	33.7 percentage of participants
Percentage of Participants Using Analgesics During the Treatment Phase Other Analgesics and Antipyretics	45.2 percentage of participants	46.4 percentage of participants	34.9 percentage of participants

Adverse Events

Elagolix 150 mg QD

Serious events: 3 serious events

Other events: 63 other events

Deaths: 0 deaths

Elagolix 75 mg BID

Serious events: 3 serious events

Other events: 59 other events

Deaths: 0 deaths

DMPA-SC

Serious events: 6 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Measure	Elagolix 150 mg QD n=84 participants at risk 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.	Elagolix 75 mg BID n=84 participants at risk 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.	DMPA-SC n=84 participants at risk 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.
Gastrointestinal disorders FOOD POISONING	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)
General disorders CHEST PAIN	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Infections and infestations APPENDICITIS	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Infections and infestations PNEUMONIA	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Metabolism and nutrition disorders DEHYDRATION	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) OVARIAN DYSGERMINOMA STAGE I	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Nervous system disorders MIGRAINE	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Psychiatric disorders DEPRESSION SUICIDAL	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Reproductive system and breast disorders PELVIC CONGESTION	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Reproductive system and breast disorders PELVIC PAIN	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)

Other adverse events

Measure	Elagolix 150 mg QD n=84 participants at risk 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.	Elagolix 75 mg BID n=84 participants at risk 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.	DMPA-SC n=84 participants at risk 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.
Gastrointestinal disorders ABDOMINAL DISTENSION	2.4% 2/84 • Number of events 2 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	7.1% 6/84 • Number of events 7 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Gastrointestinal disorders DIARRHOEA	4.8% 4/84 • Number of events 4 • From first dose of study drug through 24 weeks after last dose (48 weeks)	10.7% 9/84 • Number of events 10 • From first dose of study drug through 24 weeks after last dose (48 weeks)	9.5% 8/84 • Number of events 10 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Gastrointestinal disorders DYSPEPSIA	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)	6.0% 5/84 • Number of events 7 • From first dose of study drug through 24 weeks after last dose (48 weeks)	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Gastrointestinal disorders NAUSEA	19.0% 16/84 • Number of events 21 • From first dose of study drug through 24 weeks after last dose (48 weeks)	15.5% 13/84 • Number of events 16 • From first dose of study drug through 24 weeks after last dose (48 weeks)	15.5% 13/84 • Number of events 20 • From first dose of study drug through 24 weeks after last dose (48 weeks)
General disorders FATIGUE	6.0% 5/84 • Number of events 5 • From first dose of study drug through 24 weeks after last dose (48 weeks)	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)	7.1% 6/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Infections and infestations INFLUENZA	8.3% 7/84 • Number of events 7 • From first dose of study drug through 24 weeks after last dose (48 weeks)	6.0% 5/84 • Number of events 5 • From first dose of study drug through 24 weeks after last dose (48 weeks)	2.4% 2/84 • Number of events 2 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Infections and infestations NASOPHARYNGITIS	10.7% 9/84 • Number of events 9 • From first dose of study drug through 24 weeks after last dose (48 weeks)	21.4% 18/84 • Number of events 22 • From first dose of study drug through 24 weeks after last dose (48 weeks)	10.7% 9/84 • Number of events 11 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Infections and infestations SINUSITIS	8.3% 7/84 • Number of events 8 • From first dose of study drug through 24 weeks after last dose (48 weeks)	8.3% 7/84 • Number of events 12 • From first dose of study drug through 24 weeks after last dose (48 weeks)	7.1% 6/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	9.5% 8/84 • Number of events 10 • From first dose of study drug through 24 weeks after last dose (48 weeks)	11.9% 10/84 • Number of events 14 • From first dose of study drug through 24 weeks after last dose (48 weeks)	11.9% 10/84 • Number of events 10 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Infections and infestations URINARY TRACT INFECTION	6.0% 5/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)	9.5% 8/84 • Number of events 10 • From first dose of study drug through 24 weeks after last dose (48 weeks)	6.0% 5/84 • Number of events 5 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Infections and infestations VAGINAL MYCOSIS	6.0% 5/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)	4.8% 4/84 • Number of events 5 • From first dose of study drug through 24 weeks after last dose (48 weeks)	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Musculoskeletal and connective tissue disorders ARTHRALGIA	4.8% 4/84 • Number of events 10 • From first dose of study drug through 24 weeks after last dose (48 weeks)	10.7% 9/84 • Number of events 13 • From first dose of study drug through 24 weeks after last dose (48 weeks)	2.4% 2/84 • Number of events 2 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Musculoskeletal and connective tissue disorders BACK PAIN	7.1% 6/84 • Number of events 7 • From first dose of study drug through 24 weeks after last dose (48 weeks)	11.9% 10/84 • Number of events 11 • From first dose of study drug through 24 weeks after last dose (48 weeks)	4.8% 4/84 • Number of events 4 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Nervous system disorders DIZZINESS	3.6% 3/84 • Number of events 4 • From first dose of study drug through 24 weeks after last dose (48 weeks)	7.1% 6/84 • Number of events 8 • From first dose of study drug through 24 weeks after last dose (48 weeks)	9.5% 8/84 • Number of events 9 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Nervous system disorders HEADACHE	26.2% 22/84 • Number of events 48 • From first dose of study drug through 24 weeks after last dose (48 weeks)	27.4% 23/84 • Number of events 66 • From first dose of study drug through 24 weeks after last dose (48 weeks)	17.9% 15/84 • Number of events 64 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Nervous system disorders MIGRAINE	4.8% 4/84 • Number of events 8 • From first dose of study drug through 24 weeks after last dose (48 weeks)	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)	6.0% 5/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Psychiatric disorders ANXIETY	7.1% 6/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)	4.8% 4/84 • Number of events 4 • From first dose of study drug through 24 weeks after last dose (48 weeks)	4.8% 4/84 • Number of events 4 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Psychiatric disorders DEPRESSION	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)	7.1% 6/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)	4.8% 4/84 • Number of events 4 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Psychiatric disorders INSOMNIA	4.8% 4/84 • Number of events 4 • From first dose of study drug through 24 weeks after last dose (48 weeks)	8.3% 7/84 • Number of events 11 • From first dose of study drug through 24 weeks after last dose (48 weeks)	4.8% 4/84 • Number of events 4 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Psychiatric disorders MOOD SWINGS	8.3% 7/84 • Number of events 8 • From first dose of study drug through 24 weeks after last dose (48 weeks)	7.1% 6/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)	11.9% 10/84 • Number of events 10 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Reproductive system and breast disorders OVARIAN CYST	6.0% 5/84 • Number of events 5 • From first dose of study drug through 24 weeks after last dose (48 weeks)	0.00% 0/84 • From first dose of study drug through 24 weeks after last dose (48 weeks)	1.2% 1/84 • Number of events 1 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Respiratory, thoracic and mediastinal disorders COUGH	2.4% 2/84 • Number of events 2 • From first dose of study drug through 24 weeks after last dose (48 weeks)	7.1% 6/84 • Number of events 7 • From first dose of study drug through 24 weeks after last dose (48 weeks)	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	4.8% 4/84 • Number of events 5 • From first dose of study drug through 24 weeks after last dose (48 weeks)	7.1% 6/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Respiratory, thoracic and mediastinal disorders PHARYNGOLARYNGEAL PAIN	8.3% 7/84 • Number of events 9 • From first dose of study drug through 24 weeks after last dose (48 weeks)	8.3% 7/84 • Number of events 8 • From first dose of study drug through 24 weeks after last dose (48 weeks)	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Respiratory, thoracic and mediastinal disorders SINUS CONGESTION	3.6% 3/84 • Number of events 3 • From first dose of study drug through 24 weeks after last dose (48 weeks)	6.0% 5/84 • Number of events 6 • From first dose of study drug through 24 weeks after last dose (48 weeks)	6.0% 5/84 • Number of events 5 • From first dose of study drug through 24 weeks after last dose (48 weeks)
Skin and subcutaneous tissue disorders ACNE	8.3% 7/84 • Number of events 7 • From first dose of study drug through 24 weeks after last dose (48 weeks)	2.4% 2/84 • Number of events 2 • From first dose of study drug through 24 weeks after last dose (48 weeks)	8.3% 7/84 • Number of events 7 • From first dose of study drug through 24 weeks after last dose (48 weeks)

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