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

Phase 3

Completed

• Conditions: Endometriosis
• Interventions: Other: placebo; Drug: Elagolix

• Registration Number: NCT01931670
• Lead Sponsor: AbbVie

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2013-08-27
• Study First Submitted QC: 2013-08-27
• Study First Posted: 2013-08-29
• Study Start: 2013-09-09
• Primary Completion: 2016-01-06
• Study Completion: 2016-12-19
• Disposition First Submitted: 2016-12-22
• Disposition First Submitted QC: 2016-12-22
• Disposition First Posted: 2016-12-23
• Status Verified: 2018-03
• Results First Submitted: 2018-08-09
• Results First Submitted QC: 2018-08-09
• Last Update Submitted: 2018-08-09
• Results First Posted: 2018-09-07
• Last Update Posted: 2018-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 815

Inclusion Criteria

1. Premenopausal female, between 18 and 49 years of age, inclusive, at the time of signing consent.
2. Clinical diagnosis of endometriosis (laparoscopy or laparotomy) performed within 10 years of entry into the Washout Period.
3. Agrees to use required birth control methods during the entire length of participation in the study.
4. 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.
5. 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

1. 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.
2. 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.
3. 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.
4. Clinically significant gynecologic condition identified on Screening transvaginal ultrasound or endometrial biopsy.
5. Subject has a history of osteoporosis or other metabolic bone disease.
6. Subject has a current history of undiagnosed abnormal uterine bleeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo twice daily (BID) for the 6-month Treatment Period
Elagolix 150 mg QD	Elagolix	Elagolix 150 mg once daily (QD) for the 6-month Treatment Period
Elagolix 200 mg BID	Elagolix	Elagolix 200 mg BID for the 6-month Treatment Period

Primary Outcome Measures

Name	Time	Method
Percentage of Responders at Month 3 Based on Daily Assessment of Dysmenorrhea (DYS)	At Month 3 of the Treatment Period	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.
Percentage of Responders at Month 3 Based on Daily Assessment of Non-Menstrual Pelvic Pain (NMPP)	At Month 3 of Treatment Period	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Month 6 in DYS	Baseline, Month 6 of Treatment Period	The DYS pain scale ranges from 0 (none) to 3 (severe).
Change From Baseline to Month 6 in NMPP	Baseline, Month 6 of Treatment Period	The NMPP pain scale ranges from 0 (none) to 3 (severe).
Percent Change From Baseline to Each Month in Mean Pain Score for DYS	Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period	The DYS pain scale ranges from 0 (none) to 3 (severe).
Percent Change From Baseline to Each Month in the Mean Pain Score for NMPP	Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period	The NMPP pain scale ranges from 0 (none) to 3 (severe).
Number of Participants With Emergency Room/Outpatient Procedures During the Treatment Period, by Type	Up to Month 6 of Treatment Period	This is assessed using HRUQ.
Change From Baseline to Each Month, Except Month 3, in the Mean Pain Score of DYSP	Baseline, Months 1, 2, 4, 5, 6 of Treatment Period	The DYSP pain scale ranged from 0 (absent) to 3 (severe).
Change From Baseline to Month 3 in Numeric Rating Scale (NRS) Scores	Baseline, Month 3 of the Treatment Period	The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever).
Change From Baseline to Month 3 in Analgesic Use Across Both Classes of Rescue Analgesics	Baseline, Month 3 of Treatment Period	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.
Change From Baseline to Month 6 in Analgesic Use Across Both Classes of Rescue Analgesics	Baseline, Month 6 of Treatment Period	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.
Change From Baseline to Month 3 in Dyspareunia (DYSP)	Baseline, Month 3 of Treatment Period	The DYSP pain scale ranges from 0 (absent) to 3 (severe).
Change From Baseline to Month 3 in Use of Narcotic Class of Medication (Opioids)	Baseline, Month 3 of Treatment Period	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.
Percentage of Responders for Each Month, Except Month 3, in DYS	Months 1, 2, 4, 5, 6 of the Treatment Period	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.
Percentage of Responders for Each Month, Except Month 3, in NMPP	Months 1, 2, 4, 5, 6 of the Treatment Period	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.
Percentage of Responders at Each Month for DYSP	Months 1, 2, 3, 4, 5, 6 of Treatment Period	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.
Change From Baseline to Each Month in Health Related Productivity Questionnaire (HRPQ): Number of Hours of Work Lost From Workplace Due to Absenteeism	Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period	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.
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism	Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period	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.
Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for DYS	Baseline (Prior to administering study drug), Months 1, 2, 3, 4, 5 of Treatment Period	The DYS pain scale ranges from 0 (none) to 3 (severe).
Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for NMPP	Baseline, Months 1, 2, 3, 4, 5 of Treatment Period	The NMPP pain scale ranges from 0 (none) to 3 (severe).
Change From Baseline to Each Month, Except Months 3 and 6, in Analgesic Use Across Both Classes of Rescue Analgesics	Baseline, Months 1, 2, 4, 5	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.
Patient Global Impression of Change (PGIC) Questionnaire	Months 1, 2, 3, 4, 5, 6 of Treatment Period	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.
Change From Baseline to Each Month, Except Month 3, in NRS Scores	Baseline, Months 1, 2, 4, 5, 6 of Treatment Period	The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever).
Change From Baseline to Each Scheduled Assessment in the Pain Domain of Endometriosis Health Profile-30 (EHP-30) Questionnaire Scores	Baseline, Months 1, 3, 6 of Treatment Period	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.
Change From Baseline to Each Scheduled Assessment in the Sexual Intercourse Domain of EHP-30 Questionnaire Scores	Baseline, Months 1, 3, 6 of Treatment Period	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.
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism	Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period	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.
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism	Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period	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.
Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace	Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period	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.
Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household	Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period	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.
Number of Participants With Endometriosis-Related Non-Study Health Visits During the Treatment Period	Months 1, 2, 3, 4, 5, 6 of Treatment Period	This is assessed using Health Resource Utilization Questionnaire (HRUQ).
Number of Days of Hospitalization	Up to Month 6 of Treatment Period	This is assessed using HRUQ.