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

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00437658
• Collaborator: (none)
• Enrollment: 252
• Arms: 3
• Actual Duration (Months): 23.5

Study Details

Study Description

Brief Summary

This study is designed to assess the effects of elagolix versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC; also known as depo-provera) on bone mineral density (BMD) during treatment for 24 weeks with a subsequent 24-week post-treatment period.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis	Drug: Elagolix; Drug: Subcutaneous depot medroxyprogesterone acetate (DMPA-SC); Drug: Placebo to Elagolix; Drug: Placebo to DMPA-SC	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 252 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Double-blind, Active-controlled Study to Assess the Safety and Efficacy of NBI-56418 in Subjects With Endometriosis
• Actual Study Start Date: Dec 11, 2006
• Actual Primary Completion Date: Nov 24, 2008
• Actual Study Completion Date: Nov 24, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Elagolix; Provided as tablets for oral administration; Other Names: NBI-56418 Orilissa™ ; Drug: Placebo to DMPA-SC; Matching placebo for subcutaneous injection in a pre-filled syringe
Experimental: 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.	Drug: Elagolix; Provided as tablets for oral administration; Other Names: NBI-56418 Orilissa™ ; Drug: Placebo to DMPA-SC; Matching placebo for subcutaneous injection in a pre-filled syringe
Active Comparator: 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.	Drug: Subcutaneous depot medroxyprogesterone acetate (DMPA-SC); Provided for subcutaneous injection in a prefilled syringe, 104 mg/0.65 mL per syringe.; Other Names: depo-subQ provera 104™ ; Drug: Placebo to Elagolix; Matching placebo tablets for oral administration

Outcome Measures

Primary Outcome Measures

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

   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.

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

   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.

Secondary Outcome Measures

1. Percent Change From Baseline in Bone Mineral Density of the Spine at Weeks 12 and 48 [Baseline and weeks 12 and 48]

   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.

2. Percent Change From Baseline in Bone Mineral Density of the Femur at Weeks 12 and 48 [Baseline and weeks 12 and 48]

   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.

3. Change From Baseline in N-telopeptide at Weeks 12, 24 and 48 [Baseline and weeks 12, 24 and 48]

   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.

4. Percentage of Participants With a Response in the Dysmenorrhea Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) at Week 24 [Baseline and week 24]

   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.

5. Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS at Week 24 [Baseline and week 24]

   The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). 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.

6. Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time [Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48]

   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.

7. Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time [Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48]

   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.

8. Change From Baseline in Total CPSSS During the Treatment Period [Baseline and weeks 4, 8, 12, 16, 20, and 24]

   The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Dysmenorrhea, dyspareunia, and 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.

9. Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period [Baseline and weeks 4, 8, 12, 16, 20, and 24]

   The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Dysmenorrhea, dyspareunia, and 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.

10. Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). 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.

11. Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). 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.

12. Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). 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.

13. Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). 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.

14. Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. Each component was scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). 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.

15. Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    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.

16. Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    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.

17. Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

18. Change From Baseline in EHP-5 Control and Powerlessness Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

19. Change From Baseline in EHP-5 Emotional Well-being Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

20. Change From Baseline in EHP-5 Social Support Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

21. Change From Baseline in EHP-5 Self Image Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

22. Change From Baseline in EHP-5 Work Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

23. Change From Baseline in EHP-5 Relationship With Children Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

24. Change From Baseline in EHP-5 Intercourse Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

25. Change From Baseline in EHP-5 Medical Profession Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

26. Change From Baseline in EHP-5 Treatment Dimension [Baseline and weeks 4, 8, 12, 16, 20, and 24]

    The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the 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.

27. Percentage of Participants Using Analgesics During the Treatment Phase [24 weeks]

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

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Be female, aged 18 to 49 years, inclusive

• Have a total CPSSS of ≥ 6 at screening and baseline (Day 1) in the following categories: dysmenorrhea, dyspareunia, nonmenstrual pelvic pain, pelvic tenderness and induration. The total score must include a total of at least 2 in each of the categories of dysmenorrhea and nonmenstrual pelvic pain.

• Have had a diagnosis of endometriosis made following laparoscopic visualization of the disease within 8 years of the start of screening with recurrent or persistent symptoms.

• Have documented negative mammogram results within 12 months of screening if over the age of 40 years.

• Have menstrual cycles (28 days ±5 days). Assessment of cycle duration should be based on observations in the absence of drugs or conditions that are known to affect the cycle (e.g., oral contraceptives, leuprolide, pregnancy).

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

• Agree to use two forms of nonhormonal contraception (e.g. condom with spermicide) during the study.

Exclusion Criteria:

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

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

• Have been nonresponsive to GnRH agonist or antagonist therapy for the management of endometriosis.

• Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within 1 month of the start of screening.

• Have had surgical treatment for endometriosis (laparoscopy) within 1 month of the start of screening.

• Have had a hysterectomy or bilateral oophorectomy.

• Have had prior treatment with NBI-56418.

• Have uterine fibroids or other pelvic lesions ≥ 5 cm in diameter

• Have any of the following abnormal cervical smear results at screening (based on the 2001 Bethesda System):

• Benign endometrial cells (BEC) present, provided subject has irregular uterine bleeding or is over 40 years old

• Atypical squamous cells of undetermined significance (ASC-US) present, and human papilloma virus (HPV) reflex testing is positive for high risk types or the testing outcome is unknown

• Atypical squamous cells present, and high-grade squamous intraepithelial lesion (ASC-H) cannot be excluded

• Atypical glandular cells of uncertain significance (AGUS/AGC): not otherwise specified (NOS), favor neoplasia (FN), favor endocervical, or favor endometrial origin types

• Low-grade squamous intraepithelial lesion (LSIL) present

• High-grade squamous intraepithelial lesion (HSIL) present

• Adenocarcinoma in situ (AIS) / malignant cells present

• Have BMD with either lumbar spine or femur T-scores below -1.5 at screening as determined by the central DXA facility or have history of pathologic or compression fractures.

• Have been pregnant within 6 months of screening or currently breast feeding

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

• Have unstable medical condition or chronic disease

• Have chronic pelvic pain that is not caused by endometriosis

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT00437658
• Other Study ID Numbers: NBI-56418-0603
• First Posted: Feb 21, 2007
• Last Update Posted: Oct 12, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Endometriosis; Medroxyprogesterone Acetate; Medroxyprogesterone

Study Results

Participant Flow

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Period Title: Treatment Period (24 Weeks)
STARTED	84	84	84
Received Study Drug	84	84	84
COMPLETED	56	62	51
NOT COMPLETED	28	22	33
Period Title: Treatment Period (24 Weeks)
STARTED	56	62	51
COMPLETED	32	54	37
NOT COMPLETED	24	8	14

Baseline Characteristics

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC	Total
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.	Total of all reporting groups
Overall Participants	84	84	84	252
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.4 (7.5)	31.4 (6.1)	30.9 (6.3)	31.6 (6.7)
Sex: Female, Male (Count of Participants)
Female	84 100%	84 100%	84 100%	252 100%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	1 1.2%	0 0%	1 1.2%	2 0.8%
Black	6 7.1%	10 11.9%	10 11.9%	26 10.3%
White	68 81%	70 83.3%	65 77.4%	203 80.6%
Hispanic	8 9.5%	4 4.8%	6 7.1%	18 7.1%
American Indian or Alaska Native, Caucasian	0 0%	0 0%	1 1.2%	1 0.4%
Black, Caucasian	1 1.2%	0 0%	0 0%	1 0.4%
Caucasian, Hispanic	0 0%	0 0%	1 1.2%	1 0.4%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	55	62	50
Least Squares Mean (95% Confidence Interval) [percent change]	-0.11	-1.29	-0.99

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	56	64	51
Least Squares Mean (95% Confidence Interval) [percent change]	-0.47	-1.02	-1.29

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	84
Week 12	-0.39	-1.05	-0.57
Week 48	0.20	-0.49	-0.56

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	84
Week 12	-0.63	-0.54	-0.77
Week 48	-0.38	-0.86	-0.76

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	84
Week 12	0.94 (0.43)	0.57 (0.43)	0.74 (0.45)
Week 24	0.23 (0.50)	-0.30 (0.48)	-0.24 (0.54)
Week 48	-1.28 (0.61)	-1.53 (0.48)	-1.39 (0.58)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	57	65	51
Number [percentage of participants]	86.0 102.4%	73.8 87.9%	86.3 102.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD, DMPA-SC
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Statistical non-inferiority was defined when the lower bound of the 95% 2-sided confidence interval for the difference between an elagolix dose and DMPA-SC in the response rate was no less than -20% at week 24 for both dysmenorrhea and non-menstrual pelvic pain.
Statistical Test of Hypothesis	p-Value	0.9630
	Comments
	Method	Pearson chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -13.4 to 12.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in response rate = elogolix - DMPA-SC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID, DMPA-SC
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Statistical non-inferiority was defined when the lower bound of the 95% 2-sided confidence interval for the difference between an elagolix dose and DMPA-SC in the response rate was no less than -20% at week 24 for both dysmenorrhea and non-menstrual pelvic pain.
Statistical Test of Hypothesis	p-Value	0.1010
	Comments
	Method	Pearson chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-12.4
	Confidence Interval	(2-Sided) 95%; -26.7 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in response rate = elogolix - DMPA-SC

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	57	65	51
Number [percentage of participants]	86.0 102.4%	76.9 91.5%	76.5 91.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD, DMPA-SC
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Statistical non-inferiority was defined when the lower bound of the 95% 2-sided confidence interval for the difference between an elagolix dose and DMPA-SC in the response rate was no less than -20% at week 24 for both dysmenorrhea and non-menstrual pelvic pain.
Statistical Test of Hypothesis	p-Value	0.2048
	Comments
	Method	Pearson chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; -5.2 to 24.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in response rates = elagolix - DMPA-SC

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID, DMPA-SC
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Statistical non-inferiority was defined when the lower bound of the 95% 2-sided confidence interval for the difference between an elagolix dose and DMPA-SC in the response rate was no less than -20% at week 24 for both dysmenorrhea and non-menstrual pelvic pain.
Statistical Test of Hypothesis	p-Value	0.9544
	Comments
	Method	Pearson chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -15.1 to 16.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in response rates = elagolix - DMPA-SC

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	75.3 89.6%	80.7 96.1%	74.7 88.9%
Week 8	84.0 100%	84.0 100%	79.5 94.6%
Week 12	73.2 87.1%	82.2 97.9%	82.1 97.7%
Week 16	87.5 104.2%	82.6 98.3%	91.2 108.6%
Week 20	81.7 97.3%	76.5 91.1%	83.3 99.2%
Week 24	86.0 102.4%	73.8 87.9%	86.3 102.7%
Week 28	70.8 84.3%	57.4 68.3%	93.3 111.1%
Week 36	52.5 62.5%	44.6 53.1%	80.5 95.8%
Week 48	63.6 75.7%	58.2 69.3%	66.7 79.4%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	74.1 88.2%	56.6 67.4%	68.7 81.8%
Week 8	82.7 98.5%	76.0 90.5%	82.2 97.9%
Week 12	74.6 88.8%	82.2 97.9%	71.6 85.2%
Week 16	82.8 98.6%	78.3 93.2%	70.2 83.6%
Week 20	81.7 97.3%	80.9 96.3%	75.9 90.4%
Week 24	86.0 102.4%	76.9 91.5%	76.5 91.1%
Week 28	66.7 79.4%	60.7 72.3%	73.3 87.3%
Week 36	67.5 80.4%	60.7 72.3%	68.3 81.3%
Week 48	66.7 79.4%	56.4 67.1%	71.8 85.5%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-3.9 (0.29)	-3.7 (0.29)	-3.8 (0.29)
Week 8	-4.9 (0.30)	-4.8 (0.30)	-4.5 (0.30)
Week 12	-4.6 (0.31)	-5.1 (0.30)	-4.2 (0.31)
Week 16	-5.5 (0.32)	-5.4 (0.31)	-4.6 (0.33)
Week 20	-5.1 (0.33)	-5.3 (0.31)	-4.8 (0.34)
Week 24	-5.5 (0.34)	-5.2 (0.32)	-5.3 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in total CPSSS at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-5.5
	Confidence Interval	(2-Sided) 95%; -6.2 to -4.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in total CPSSS at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-5.2
	Confidence Interval	(2-Sided) 95%; -5.8 to -4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in total CPSSS at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-5.3
	Confidence Interval	(2-Sided) 95%; -6.0 to -4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-3.4 (0.25)	-3.4 (0.25)	-3.3 (0.25)
Week 8	-4.1 (0.26)	-4.2 (0.26)	-3.8 (0.26)
Week 12	-3.8 (0.26)	-4.4 (0.26)	-3.7 (0.27)
Week 16	-4.6 (0.27)	-4.6 (0.27)	-3.9 (0.29)
Week 20	-4.4 (0.28)	-4.4 (0.27)	-4.1 (0.30)
Week 24	-4.6 (0.29)	-4.4 (0.28)	-4.5 (0.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in total CPSSS excluding dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-4.6
	Confidence Interval	(2-Sided) 95%; -5.1 to -4.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in total CPSSS excluding dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -5.0 to -3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in total CPSSS excluding dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -5.1 to -3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-1.4 (0.11)	-1.5 (0.11)	-1.3 (0.11)
Week 8	-1.6 (0.11)	-1.7 (0.11)	-1.5 (0.12)
Week 12	-1.3 (0.12)	-1.7 (0.12)	-1.5 (0.12)
Week 16	-1.6 (0.12)	-1.8 (0.12)	-1.8 (0.13)
Week 20	-1.4 (0.13)	-1.5 (0.12)	-1.4 (0.13)
Week 24	-1.5 (0.13)	-1.4 (0.12)	-1.7 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in dysmenorrhea at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -1.7 to -1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in dysmenorrhea at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -1.6 to -1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in dysmenorrhea at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -1.9 to -1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-0.6 (0.11)	-0.4 (0.13)	-0.5 (0.11)
Week 8	-0.9 (0.12)	-0.7 (0.13)	-0.8 (0.12)
Week 12	-1.0 (0.12)	-0.8 (0.13)	-0.6 (0.12)
Week 16	-1.2 (0.13)	-1.0 (0.13)	-0.8 (0.14)
Week 20	-0.9 (0.13)	-1.0 (0.14)	-0.8 (0.14)
Week 24	-1.2 (0.13)	-1.0 (0.14)	-0.8 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 2%; -1.2 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in dyspareunia at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-0.9 (0.09)	-0.8 (0.09)	-0.8 (0.09)
Week 8	-1.1 (0.09)	-1.1 (0.09)	-1.1 (0.09)
Week 12	-1.0 (0.09)	-1.1 (0.09)	-0.9 (0.10)
Week 16	-1.2 (0.10)	-1.2 (0.09)	-0.9 (0.10)
Week 20	-1.1 (0.10)	-1.3 (0.10)	-1.0 (0.11)
Week 24	-1.2 (0.10)	-1.2 (0.10)	-1.1 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in non-menstrual pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -1.4 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in non-menstrual pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -1.4 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in non-menstrual pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.3 to -0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-0.6 (0.08)	-0.7 (0.08)	-0.7 (0.08)
Week 8	-0.8 (0.09)	-0.8 (0.08)	-0.7 (0.09)
Week 12	-0.8 (0.09)	-0.9 (0.09)	-0.7 (0.09)
Week 16	-1.0 (0.09)	-0.9 (0.09)	-0.6 (0.09)
Week 20	-1.0 (0.09)	-0.8 (0.09)	-0.9 (0.10)
Week 24	-1.0 (0.09)	-1.0 (0.09)	-0.9 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in pelvic tenderness at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in pelvic tenderness at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in pelvic tenderness at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-0.4 (0.08)	-0.5 (0.08)	-0.5 (0.08)
Week 8	-0.7 (0.08)	-0.6 (0.08)	-0.6 (0.08)
Week 12	-0.7 (0.08)	-0.8 (0.08)	-0.6 (0.08)
Week 16	-0.9 (0.09)	-0.8 (0.08)	-0.7 (0.09)
Week 20	-0.9 (0.09)	-0.8 (0.08)	-0.8 (0.09)
Week 24	-0.9 (0.09)	-0.9 (0.09)	-0.8 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in pelvic induration at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.0 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in pelvic induration at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in pelvic induration at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-18.2 (2.97)	-14.4 (2.96)	-15.4 (2.98)
Week 8	-26.3 (3.06)	-28.1 (3.02)	-27.1 (3.08)
Week 12	-31.3 (3.14)	-32.7 (3.09)	-24.9 (3.20)
Week 16	-32.1 (3.24)	-37.8 (3.19)	-30.8 (3.38)
Week 20	-29.0 (3.40)	-37.9 (3.23)	-31.0 (3.51)
Week 24	-32.3 (3.51)	-32.9 (3.31)	-35.8 (3.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in peak VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-32.3
	Confidence Interval	(2-Sided) 95%; -39.2 to -25.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in peak VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-32.9
	Confidence Interval	(2-Sided) 95%; -39.4 to -26.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in peak VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-35.8
	Confidence Interval	(2-Sided) 95%; -43.0 to -28.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-10.2 (1.59)	-11.7 (1.58)	-10.2 (1.59)
Week 8	-14.0 (2.09)	-17.8 (2.06)	-15.9 (2.10)
Week 12	-17.7 (2.24)	-23.4 (2.19)	-15.5 (2.27)
Week 16	-17.8 (2.51)	-23.6 (2.45)	-17.3 (2.57)
Week 20	-16.6 (2.53)	-24.1 (2.43)	-17.1 (2.59)
Week 24	-18.2 (2.57)	-23.4 (2.47)	-17.9 (2.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elagolix 150 mg QD
	Comments	Within-group analysis of change from baseline in monthly mean VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-18.2
	Confidence Interval	(2-Sided) 95%; -23.3 to -13.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elagolix 75 mg BID
	Comments	Within-group analysis of change from baseline in monthly mean VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-23.4
	Confidence Interval	(2-Sided) 95%; -28.3 to -18.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DMPA-SC
	Comments	Within-group analysis of change from baseline in peak VAS for pelvic pain at week 24. Change from baseline was analyzed using a mixed-effects repeated measures (MERM) analysis of covariance model which included fixed effects for treatment, time, treatment-by-time interaction, a random effect for patient, and terms for baseline value and the baseline-by-time interaction.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value for test of null hypothesis that the treatment group least squares mean is equal to zero.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-17.9
	Confidence Interval	(2-Sided) 95%; -23.1 to -12.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-20.7 (2.4)	-22.9 (2.6)	-18.7 (2.5)
Week 8	-22.0 (3.1)	-30.0 (2.5)	-24.3 (2.6)
Week 12	-23.2 (3.1)	-28.4 (3.2)	-25.4 (3.4)
Week 16	-30.9 (3.1)	-31.9 (2.8)	-29.8 (3.7)
Week 20	-26.3 (3.8)	-29.8 (2.8)	-28.3 (3.6)
Week 24	-28.9 (3.2)	-28.5 (3.2)	-30.9 (4.1)

20. Secondary Outcome

Title	Change From Baseline in EHP-5 Control and Powerlessness Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-19.8 (2.9)	-24.7 (3.0)	-22.9 (2.6)
Week 8	-27.7 (3.1)	-33.0 (3.5)	-31.2 (3.5)
Week 12	-30.6 (3.3)	-31.2 (3.8)	-26.1 (4.0)
Week 16	-34.4 (3.7)	-33.3 (3.8)	-31.1 (4.3)
Week 20	-32.9 (3.8)	-33.1 (4.2)	-34.9 (4.4)
Week 24	-37.3 (3.8)	-33.1 (3.8)	-35.8 (5.0)

21. Secondary Outcome

Title	Change From Baseline in EHP-5 Emotional Well-being Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-12.7 (2.5)	-10.4 (2.7)	-5.1 (2.8)
Week 8	-20.6 (2.7)	-16.0 (3.1)	-13.4 (2.9)
Week 12	-18.0 (3.0)	-21.9 (3.2)	-14.6 (2.6)
Week 16	-21.1 (3.3)	-20.7 (3.6)	-14.9 (3.7)
Week 20	-20.8 (3.7)	-22.8 (3.1)	-18.4 (3.8)
Week 24	-24.1 (3.6)	-23.8 (3.4)	-25.5 (4.2)

22. Secondary Outcome

Title	Change From Baseline in EHP-5 Social Support Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-25.3 (3.0)	-26.5 (3.4)	-19.6 (2.9)
Week 8	-31.4 (3.5)	-33.7 (3.9)	-29.8 (3.4)
Week 12	-36.8 (3.7)	-34.6 (4.4)	-28.4 (3.6)
Week 16	-42.2 (4.0)	-37.0 (4.3)	-32.0 (3.7)
Week 20	-42.1 (4.2)	-39.0 (4.4)	-34.9 (3.9)
Week 24	-43.4 (4.1)	-40.0 (4.4)	-32.8 (5.1)

23. Secondary Outcome

Title	Change From Baseline in EHP-5 Self Image Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-11.1 (3.3)	-20.1 (2.9)	-11.1 (3.5)
Week 8	-19.6 (3.3)	-22.7 (3.3)	-17.5 (3.8)
Week 12	-21.1 (4.0)	-22.6 (3.2)	-18.3 (4.1)
Week 16	-20.3 (3.6)	-25.7 (3.1)	-18.9 (3.9)
Week 20	-20.8 (4.3)	-26.1 (3.4)	-19.3 (4.4)
Week 24	-23.7 (4.1)	-26.9 (3.8)	-24.5 (4.9)

24. Secondary Outcome

Title	Change From Baseline in EHP-5 Work Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-20.5 (3.2)	-20.9 (2.8)	-21.0 (2.6)
Week 8	-21.2 (3.5)	-25.8 (3.1)	-25.8 (3.3)
Week 12	-21.8 (3.8)	-24.2 (3.3)	-25.4 (3.7)
Week 16	-24.6 (3.9)	-26.6 (3.2)	-26.6 (4.0)
Week 20	-24.1 (4.2)	-27.5 (3.1)	-29.4 (4.1)
Week 24	-24.0 (4.0)	-26.7 (3.1)	-27.8 (4.2)

25. Secondary Outcome

Title	Change From Baseline in EHP-5 Relationship With Children Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-16.1 (4.4)	-18.9 (3.8)	-16.1 (3.9)
Week 8	-19.9 (4.5)	-20.8 (3.8)	-24.4 (3.9)
Week 12	-23.0 (4.8)	-20.7 (4.2)	-28.6 (4.8)
Week 16	-24.2 (4.7)	-26.6 (4.2)	-25.8 (5.0)
Week 20	-27.8 (4.3)	-25.0 (4.1)	-28.6 (5.7)
Week 24	-29.8 (4.6)	-23.3 (4.3)	-31.7 (6.0)

26. Secondary Outcome

Title	Change From Baseline in EHP-5 Intercourse Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-17.3 (3.3)	-18.5 (3.6)	-17.4 (3.3)
Week 8	-25.8 (3.5)	-27.2 (3.8)	-20.5 (4.3)
Week 12	-29.1 (3.7)	-29.5 (4.0)	-20.5 (4.4)
Week 16	-31.7 (4.3)	-29.2 (3.8)	-23.3 (5.1)
Week 20	-30.7 (4.4)	-31.7 (4.2)	-25.0 (5.2)
Week 24	-35.3 (4.4)	-33.9 (4.4)	-29.5 (5.4)

27. Secondary Outcome

Title	Change From Baseline in EHP-5 Medical Profession Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-13.2 (3.4)	-9.1 (2.6)	-12.0 (2.6)
Week 8	-15.3 (3.0)	-14.7 (3.2)	-13.5 (3.2)
Week 12	-16.7 (3.4)	-14.2 (3.7)	-15.0 (3.2)
Week 16	-18.9 (3.6)	-14.4 (3.4)	-17.9 (3.5)
Week 20	-18.2 (3.8)	-14.6 (3.2)	-15.6 (3.8)
Week 24	-18.8 (3.5)	-14.0 (3.5)	-16.0 (4.1)

28. Secondary Outcome

Title	Change From Baseline in EHP-5 Treatment Dimension
Description	The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts: A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image A supplemental questionnaire consisting of six additional questions, five of which were recorded in this study: work, relationship with children, sexual intercourse, feelings about the medical profession and treatment. Each question was scored on a five point scale (Never = 0, Rarely = 25, Sometimes = 50, Often = 75, Always = 100), or Not Relevant (no score), where 0 indicates the best health status and 100 worst health status. A negative change from baseline score indicates improvement in quality of life.
Time Frame	Baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Week 4	-27.4 (5.1)	-30.2 (4.5)	-26.8 (4.4)
Week 8	-32.8 (6.3)	-37.0 (4.8)	-29.8 (4.8)
Week 12	-35.0 (6.0)	-37.2 (5.5)	-28.0 (5.3)
Week 16	-36.8 (6.9)	-38.3 (4.6)	-28.6 (6.4)
Week 20	-35.7 (6.6)	-34.8 (5.2)	-35.6 (6.3)
Week 24	-35.6 (7.1)	-39.3 (5.0)	-28.9 (7.3)

29. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Elagolix 150 mg QD	Elagolix 75 mg BID	DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.	Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
Measure Participants	84	84	83
Antiinflammatory/Antirheumatics, Non-Steroids	65.5 78%	64.3 76.5%	68.7 81.8%
Opioids	23.8 28.3%	25.0 29.8%	33.7 40.1%
Other Analgesics and Antipyretics	45.2 53.8%	46.4 55.2%	34.9 41.5%

Adverse Events

Time Frame	From first dose of study drug through 24 weeks after last dose (48 weeks)
Arm/Group Title	Elagolix 150 mg QD		Elagolix 75 mg BID		DMPA-SC
Arm/Group Description	Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.		Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.		Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
All Cause Mortality
	Elagolix 150 mg QD		Elagolix 75 mg BID		DMPA-SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/84 (0%)		0/84 (0%)
Serious Adverse Events
	Elagolix 150 mg QD		Elagolix 75 mg BID		DMPA-SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/84 (3.6%)		3/84 (3.6%)		6/84 (7.1%)
Gastrointestinal disorders
FOOD POISONING	0/84 (0%)	0	0/84 (0%)	0	1/84 (1.2%)	1
General disorders
CHEST PAIN	0/84 (0%)	0	0/84 (0%)	0	1/84 (1.2%)	1
Infections and infestations
APPENDICITIS	0/84 (0%)	0	0/84 (0%)	0	1/84 (1.2%)	1
PNEUMONIA	0/84 (0%)	0	1/84 (1.2%)	1	0/84 (0%)	0
Metabolism and nutrition disorders
DEHYDRATION	1/84 (1.2%)	1	0/84 (0%)	0	0/84 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OVARIAN DYSGERMINOMA STAGE I	1/84 (1.2%)	1	0/84 (0%)	0	0/84 (0%)	0
Nervous system disorders
MIGRAINE	0/84 (0%)	0	1/84 (1.2%)	1	0/84 (0%)	0
Psychiatric disorders
DEPRESSION SUICIDAL	0/84 (0%)	0	1/84 (1.2%)	1	0/84 (0%)	0
Reproductive system and breast disorders
PELVIC CONGESTION	0/84 (0%)	0	0/84 (0%)	0	1/84 (1.2%)	1
PELVIC PAIN	1/84 (1.2%)	1	0/84 (0%)	0	1/84 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX	0/84 (0%)	0	0/84 (0%)	0	1/84 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Elagolix 150 mg QD		Elagolix 75 mg BID		DMPA-SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/84 (75%)		59/84 (70.2%)		63/84 (75%)
Gastrointestinal disorders
ABDOMINAL DISTENSION	2/84 (2.4%)	2	0/84 (0%)	0	6/84 (7.1%)	7
DIARRHOEA	4/84 (4.8%)	4	9/84 (10.7%)	10	8/84 (9.5%)	10
DYSPEPSIA	1/84 (1.2%)	1	5/84 (6%)	7	3/84 (3.6%)	3
NAUSEA	16/84 (19%)	21	13/84 (15.5%)	16	13/84 (15.5%)	20
General disorders
FATIGUE	5/84 (6%)	5	3/84 (3.6%)	3	6/84 (7.1%)	6
Infections and infestations
INFLUENZA	7/84 (8.3%)	7	5/84 (6%)	5	2/84 (2.4%)	2
NASOPHARYNGITIS	9/84 (10.7%)	9	18/84 (21.4%)	22	9/84 (10.7%)	11
SINUSITIS	7/84 (8.3%)	8	7/84 (8.3%)	12	6/84 (7.1%)	6
UPPER RESPIRATORY TRACT INFECTION	8/84 (9.5%)	10	10/84 (11.9%)	14	10/84 (11.9%)	10
URINARY TRACT INFECTION	5/84 (6%)	6	8/84 (9.5%)	10	5/84 (6%)	5
VAGINAL MYCOSIS	5/84 (6%)	6	4/84 (4.8%)	5	3/84 (3.6%)	3
Musculoskeletal and connective tissue disorders
ARTHRALGIA	4/84 (4.8%)	10	9/84 (10.7%)	13	2/84 (2.4%)	2
BACK PAIN	6/84 (7.1%)	7	10/84 (11.9%)	11	4/84 (4.8%)	4
Nervous system disorders
DIZZINESS	3/84 (3.6%)	4	6/84 (7.1%)	8	8/84 (9.5%)	9
HEADACHE	22/84 (26.2%)	48	23/84 (27.4%)	66	15/84 (17.9%)	64
MIGRAINE	4/84 (4.8%)	8	3/84 (3.6%)	3	5/84 (6%)	6
Psychiatric disorders
ANXIETY	6/84 (7.1%)	6	4/84 (4.8%)	4	4/84 (4.8%)	4
DEPRESSION	3/84 (3.6%)	3	6/84 (7.1%)	6	4/84 (4.8%)	4
INSOMNIA	4/84 (4.8%)	4	7/84 (8.3%)	11	4/84 (4.8%)	4
MOOD SWINGS	7/84 (8.3%)	8	6/84 (7.1%)	6	10/84 (11.9%)	10
Reproductive system and breast disorders
OVARIAN CYST	5/84 (6%)	5	0/84 (0%)	0	1/84 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	2/84 (2.4%)	2	6/84 (7.1%)	7	3/84 (3.6%)	3
NASAL CONGESTION	4/84 (4.8%)	5	6/84 (7.1%)	6	3/84 (3.6%)	3
PHARYNGOLARYNGEAL PAIN	7/84 (8.3%)	9	7/84 (8.3%)	8	3/84 (3.6%)	3
SINUS CONGESTION	3/84 (3.6%)	3	5/84 (6%)	6	5/84 (6%)	5
Skin and subcutaneous tissue disorders
ACNE	7/84 (8.3%)	7	2/84 (2.4%)	2	7/84 (8.3%)	7

Limitations/Caveats

[Not Specified]

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

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.