A Global Phase 3 Study to Evaluate the Safety and Efficacy of Elagolix in Subjects With Moderate to Severe Endometriosis-Associated Pain

Study Overview
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Brief Summary
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A randomized study evaluating the safety and efficacy of elagolix in the management of moderate to severe endometriosis-associated pain in adult premenopausal female subjects.

Detailed Description
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The study consists of 4 periods: 1) Washout Period (if applicable); 2) a Screening Period of up to 100 days prior to first dose; 3) a 6 month Treatment Period; and 4) a Post treatment Follow-up Period of up to 12 months (if applicable). An electronic diary will be dispensed and training provided to record endometriosis-associated pain, uterine bleeding, and analgesic medication use for endometriosis-associated pain on a daily basis. Pregnancy testing will be performed monthly throughout the study. Subjects will be required to use nonhormonal dual contraception during the study, and will be counseled on appropriate and effective forms of birth control to promote pregnancy prevention.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Elagolix in Subjects With Moderate to Severe Endometriosis-Associated Pain

Conditions
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Endometriosis

Intervention / Treatment
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* Other: placebo
* Drug: Elagolix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal female, between 18 and 49 years of age, inclusive, at the time of signing consent. Clinical diagnosis of endometriosis (laparoscopy or laparotomy) performed within 10 years of entry into the Washout Period. Agrees to use required birth control methods during the entire length of participation in the study. Subject has a Composite Pelvic Signs and Symptoms Score total score of 6 or greater at Screening with a score of at least 2 for dysmenorrhea AND at least 2 for non-menstrual pelvic pain. Subjects must have at least two regular menstrual cycles with an interval of 24-38 days within the Screening Period, prior to Day 1. Exclusion Criteria: Subject is pregnant or breast feeding or is planning a pregnancy within the next 24 months or is less than 6 months postpartum, post-abortion, or post-pregnancy at the time of entry into the Screening Period. Subject has a history of previous non-response to gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, Depot medroxyprogesterone acetate, or aromatase inhibitors as assessed by subject report of no improvement in dysmenorrhea or non-menstrual pelvic pain. Subject has chronic pelvic pain that is not caused by endometriosis that requires chronic analgesic or other chronic therapy, or that would interfere with the assessment of endometriosis related pain. Clinically significant gynecologic condition identified on Screening transvaginal ultrasound or endometrial biopsy. Subject has a history of osteoporosis or other metabolic bone disease. Subject has a current history of undiagnosed abnormal uterine bleeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo twice daily (BID) for the 6-month Treatment Period | Other: placebo<br> <br> |
| Experimental: Elagolix 150 mg QD<br>Elagolix 150 mg once daily (QD) for the 6-month Treatment Period | Drug: Elagolix<br> <br> * Other names: elagolix sodium;|
| Experimental: Elagolix 200 mg BID<br>Elagolix 200 mg BID for the 6-month Treatment Period | Drug: Elagolix<br> <br> * Other names: elagolix sodium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders at Month 3 Based on Daily Assessment of Dysmenorrhea (DYS) | The DYS pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.85 or greater from Baseline in DYS pain as well as no increased rescue analgesic use for endometriosis-associated pain. | At Month 3 of the Treatment Period | 
| Percentage of Responders at Month 3 Based on Daily Assessment of Non-Menstrual Pelvic Pain (NMPP) | The NMPP pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.43 or greater from Baseline in NMPP as well as no increased rescue analgesic use for endometriosis-associated pain. | At Month 3 of Treatment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders for Each Month, Except Month 3, in NMPP | The NMPP pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.43 or greater from Baseline in NMPP as well as no increased rescue analgesic use for endometriosis-associated pain. | Months 1, 2, 4, 5, 6 of the Treatment Period | 
| Percentage of Responders at Each Month for DYSP | The DYSP pain scale ranged from 0 (absent) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.29 or greater from Baseline in DYSP as well as no increased rescue analgesic use for endometriosis-associated pain. | Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for DYS | The DYS pain scale ranges from 0 (none) to 3 (severe). | Baseline (Prior to administering study drug), Months 1, 2, 3, 4, 5 of Treatment Period | 
| Percent Change From Baseline to Each Month in Mean Pain Score for DYS | The DYS pain scale ranges from 0 (none) to 3 (severe). | Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for NMPP | The NMPP pain scale ranges from 0 (none) to 3 (severe). | Baseline, Months 1, 2, 3, 4, 5 of Treatment Period | 
| Percent Change From Baseline to Each Month in the Mean Pain Score for NMPP | The NMPP pain scale ranges from 0 (none) to 3 (severe). | Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month, Except Month 3, in the Mean Pain Score of DYSP | The DYSP pain scale ranged from 0 (absent) to 3 (severe). | Baseline, Months 1, 2, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month, Except Months 3 and 6, in Analgesic Use Across Both Classes of Rescue Analgesics | Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts. | Baseline, Months 1, 2, 4, 5 | 
| Patient Global Impression of Change (PGIC) Questionnaire | The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug. | Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month, Except Month 3, in NRS Scores | The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). | Baseline, Months 1, 2, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Scheduled Assessment in the Pain Domain of Endometriosis Health Profile-30 (EHP-30) Questionnaire Scores | The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. | Baseline, Months 1, 3, 6 of Treatment Period | 
| Change From Baseline to Each Scheduled Assessment in the Sexual Intercourse Domain of EHP-30 Questionnaire Scores | The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. | Baseline, Months 1, 3, 6 of Treatment Period | 
| Change From Baseline to Each Month in Health Related Productivity Questionnaire (HRPQ): Number of Hours of Work Lost From Workplace Due to Absenteeism | The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration. | Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism | The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration. | Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism | The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration. | Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism | The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration. | Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace | The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration. | Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household | The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration. | Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Number of Participants With Endometriosis-Related Non-Study Health Visits During the Treatment Period | This is assessed using Health Resource Utilization Questionnaire (HRUQ). | Months 1, 2, 3, 4, 5, 6 of Treatment Period | 
| Number of Days of Hospitalization | This is assessed using HRUQ. | Up to Month 6 of Treatment Period | 
| Number of Participants With Emergency Room/Outpatient Procedures During the Treatment Period, by Type | This is assessed using HRUQ. | Up to Month 6 of Treatment Period | 
| Change From Baseline to Month 3 in Use of Narcotic Class of Medication (Opioids) | Permitted country-specific rescue narcotic analgesics included 5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen. Assessment was based on average pill counts. | Baseline, Month 3 of Treatment Period | 
| Percentage of Responders for Each Month, Except Month 3, in DYS | The DYS pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.85 or greater from Baseline in DYS pain as well as no increased rescue analgesic use for endometriosis-associated pain. | Months 1, 2, 4, 5, 6 of the Treatment Period | 
| Change From Baseline to Month 3 in Analgesic Use Across Both Classes of Rescue Analgesics | Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts. | Baseline, Month 3 of Treatment Period | 
| Change From Baseline to Month 6 in Analgesic Use Across Both Classes of Rescue Analgesics | Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts. | Baseline, Month 6 of Treatment Period | 
| Change From Baseline to Month 3 in Dyspareunia (DYSP) | The DYSP pain scale ranges from 0 (absent) to 3 (severe). | Baseline, Month 3 of Treatment Period | 
| Change From Baseline to Month 6 in NMPP | The NMPP pain scale ranges from 0 (none) to 3 (severe). | Baseline, Month 6 of Treatment Period | 
| Change From Baseline to Month 3 in Numeric Rating Scale (NRS) Scores | The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). | Baseline, Month 3 of the Treatment Period | 
| Change From Baseline to Month 6 in DYS | The DYS pain scale ranges from 0 (none) to 3 (severe). | Baseline, Month 6 of Treatment Period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Menstrual Pelvic Pain (NMPP), Dysmenorrhea (DYS), Elagolix, Endometriosis Associated Pain, Gonadotropin-Releasing Hormone Antagonist