An Efficacy and Safety Study of Elagolix (NBI-56418) in Women With Endometriosis

Study Overview
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Brief Summary
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This study is designed to see how elagolix works compared to placebo in women with endometriosis and to see the effect, if any, on bone mineral density.

Detailed Description
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This is a Phase II, multicenter, randomized, double-blind, placebo-controlled parallel-group study to assess the efficacy and safety of elagolix at two dose levels administered once daily for up to 6 months. Participants will be randomized (1:1:1) to one of the following treatment groups for the first 12 weeks of dosing: 150 mg elagolix once daily (QD); 250 mg elagolix QD or placebo QD. Following 12 weeks of dosing, participants will continue in the study for an additional 12 weeks; participants randomized to elagolix will continue to receive their assigned dose and participants randomized to placebo will be re-randomized to receive one of the two doses of elagolix for 12 weeks in a double-blind fashion. Six weeks after the last dose of study drug at the end of Week 24, a follow-up visit will be performed (end of Week 30).

Official Title
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A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NBI-56418 in Subjects With Endometriosis

Conditions
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Endometriosis, Pain

Intervention / Treatment
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* Drug: Elagolix
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be female, aged 18 to 49 years, inclusive Have moderate to severe pelvic pain due to endometriosis Have been surgically (laparoscopy) diagnosed with endometriosis within the last 8 years and have recurrent or persistent endometriosis symptoms Have regular menstrual cycle Have a body mass index (BMI) of 18 to 36 kg/m², inclusive Agree to use two forms of non-hormonal contraception during the study Exclusion Criteria: Are currently receiving gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist 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 Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within the last month Have had surgery for endometriosis within the last month Have had a hysterectomy or bilateral oophorectomy Are using systemic steroids on a chronic or regular basis within 3 months Have uterine fibroids ≥ 3 cm in diameter Have pelvic pain that is not caused by endometriosis Have unstable medical condition or chronic disease Have been pregnant within the last six months Currently breast feeding

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>Participants received placebo tablets once a day for 12 weeks. At the end of 12 weeks participants were re-randomized to receive one of the two doses of elagolix (150 mg or 250 mg) QD for 12 weeks. | Drug: placebo<br>* Placebo tablet administered orally<br>|
| Experimental: Elagolix 150 mg<br>Participants received elagolix 150 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg QD for an additional 12 weeks. | Drug: Elagolix<br>* Elagolix tablets administered orally<br>* Other names: Orilissa™;|
| Experimental: Elagolix 250 mg<br>Participants received elagolix 250 mg tablets once a day for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks. | Drug: Elagolix<br>* Elagolix tablets administered orally<br>* Other names: Orilissa™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain at Week 12 | The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit. | Baseline and weeks 4 and 8 | 
| Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit. | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time every day in an e-Diary according to the following response options: 0 = No pelvic pain 1 = Mild pelvic pain; subject could not do some of the things she usually does 2 = Moderate pelvic pain; subject could not do many of the things she usually does 3 = Severe pelvic pain; subject could not do most or all of the things she usually does. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit. | Baseline and weeks 4, 8, and 12 | 
| Change From Baseline in the Monthly Mean Dysmenorrhea Score | Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day in an e-Diary according to the following response options: Subject is not having her period 0 = No pain related to period 1 = Mild pain related to period; subject could not do some of the things she usually does 2 = Moderate pain related to period; subject could not do many of the things she usually does 3 = Severe pain related to period; subject could not do most of or all of the things she usually does. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit. | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in the Monthly Mean Total of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Participants assessed dysmenorrhea and pelvic pain not related to menses and their impact on daily activities at approximately the same time every day on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe) in an e-Diary. The sum of the dysmenorrhea and non-menstrual pelvic pain scores on each day were calculated to create a daily total score. On days the participant was not having her period, the dysmenorrhea score was not defined; hence, the total score was equal to the non-menstrual pelvic pain score (range 0 to 3). On days where the participant recorded menstruation the total score ranged from 0 to 6, where higher scores indicate more severe pain. The monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores is the average of the daily values reported during the 4 weeks prior to each visit. | Baseline and Weeks 4, 8, and 12 | 
| Percentage of Days With No Pain Based on NRS | The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The percentage of days a participant reported a value of zero (or no pain) for the NRS was calculated for the 4 weeks prior to each visit. | Baseline and weeks 4, 8 and 12 | 
| Percentage of Days With No Pain Based Based on Non-menstrual Pelvic Pain Daily Assessment | Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time every day in an e-Diary according to the following response options: 0 = No pelvic pain 1 = Mild pelvic pain; subject could not do some of the things she usually does 2 = Moderate pelvic pain; subject could not do many of the things she usually does 3 = Severe pelvic pain; subject could not do most or all of the things she usually does. The percentage of days a participant reported a value of zero (no pain) for non-menstrual pelvic pain was calculated for the 4 weeks prior to each visit. | Baseline and weeks 4, 8 and 12 | 
| Percentage of Days With No Pain Based Based on Dysmenorrhea Daily Assessment | Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day in an e-Diary according to the following response options: Subject is not having her period 0 = No pain related to period 1 = Mild pain related to period; subject could not do some of the things she usually does 2 = Moderate pain related to period; subject could not do many of the things she usually does = Severe pain related to period; subject could not do most of or all of the things she usually does. The percentage of days a participant reported a value of zero (no pain) for dysmenorrhea was calculated for the 4 weeks prior to each visit. | Baseline and weeks 4, 8 and 12 | 
| Percentage of Days With No Pain Based Based on Total Score of Non-menstrual Pelvic Pain and Dysmenorrhea Daily Assessment | Participants assessed dysmenorrhea and pelvic pain not related to menses and their impact on daily activities at approximately the same time every day in an e-Diary on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The sum of the dysmenorrhea and non-menstrual pelvic pain scores on each day were calculated to create a daily total score. On days the participant was not having her period, the dysmenorrhea score was not defined; hence, the total score was equal to the non-menstrual pelvic pain score (range 0 to 3). On days where the participant recorded menstruation the total score ranged from 0 to 6, where higher scores indicate more severe pain. The percentage of days a participant reported a value of zero (no pain) for the non-menstrual pelvic pain and dysmenorrhea total score was calculated for the 4 weeks prior to each visit. | Baseline and weeks 4, 8 and 12 | 
| Change From Baseline in the Percentage of Days of Any Analgesic Use | The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of any analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of an analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of none). | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in the Percentage of Days of Prescription Analgesic Use | The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of prescription analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of a prescription analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of none). | Baseline and Weeks 4, 8, and 12 | 
| Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic. The percentage of days of narcotic analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of a narcotic analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of none). | Baseline and Weeks 4, 8, and 12 | 
| Percentage of Participants With 30% Decrease From Baseline in Monthly Mean NRS | The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit. | Baseline and weeks 4, 8 and 12 | 
| Percentage of Participants With 30% Decrease From Baseline in Monthly Peak NRS | The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit. | Baseline and weeks 4, 8 and 12 | 
| Percentage of Participants With 50% Decrease From Baseline in Monthly Mean NRS | The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly mean NRS is the average of the daily values reported during the 4 weeks prior to each visit. | Baseline and weeks 4, 8 and 12 | 
| Percentage of Participants With 50% Decrease From Baseline in Monthly Peak NRS | The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day. The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit. | Baseline and weeks 4, 8 and 12 | 
| Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess dyspareunia (painful intercourse) participants were asked to select the best description of pain during sexual intercourse over the past 28 days using the following response categories: 0 = Absent; No discomfort during sexual intercourse. 1 = Mild; I can tolerate the discomfort during sexual intercourse. 2 = Moderate; Intercourse is sometime interrupted due to pain. 3 = Severe; I prefer to avoid intercourse because of pain. Not applicable. I am not sexually active for reasons other than my endometriosis symptoms. | Baseline and Weeks 4, 8, and 12 | 
| Patient Global Impression of Change at Weeks 4, 8 and 12 | The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse | Weeks 4, 8, and 12 | 
| Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse | Weeks 4, 8, and 12 | 
| Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories: Very Much Improved Much Improved Minimally Improved Not Changed Minimally Worse Much Worse Very Much Worse | Weeks 4, 8, and 12 | 
| Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | 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 with five response categories for each item (Never, Rarely, Sometimes, Often, Always) A supplemental questionnaire consisting of six additional questions which assess the areas of work, relationship with children, sexual intercourse, feelings about the medical profession, treatment, and infertility with the same five response categories plus an additional response category of Not Relevant which was not scored. The scores associated with each possible outcome category are as follows: never (0), rarely (25), sometimes (50), often (75), and always (100). A negative change from baseline score indicates improvement in quality of life. | Baseline and week 12 | 
| Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12 | Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA). | Baseline and week 12 | 
| Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 | Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA). | Baseline and Week 24 | 
| Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12 | Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA). | Baseline and week 12 | 
| Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 | Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA). | Baseline and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone mineral density, Pelvic Pain, estradiol, NBI-56418