A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NBI-56418 Sodium in Subjects With Endometriosis
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 137
- Primary Endpoint
- Change From Baseline in the Monthly Mean Cumulative Pain Score During the Double-Blind Treatment Phase
Study Overview
Brief Summary
The purpose of this study is to evaluate elagolix (NBI-56418) compared to placebo for its effects on endometriosis related pelvic pain and its safety.
Detailed Description
Participants were randomized (1:1) to 150 mg elagolix once daily or placebo once daily for the first 8 weeks of the study. Following 8 weeks of dosing, participants continued in the study for an additional 16 weeks in an open-label phase where all participants still enrolled in the study received 150 mg elagolix once daily.
There was no pre-specified primary efficacy end point for this study as there is no single key efficacy outcome measure in this exploratory Phase 2 study. However, the efficacy measures of primary interest included the daily assessment of dysmenorrhea, non-menstrual pelvic pain and dyspareunia on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) using an e-Diary.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 49 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Be female, aged 18 to 49 years, inclusive.
- •Have moderate to severe pelvic pain due to endometriosis.
- •Have a history of regular menstrual cycles.
- •Have been surgically (laparoscopy or laparotomy) diagnosed with endometriosis within 8 years of the start of screening.
- •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, a GnRH antagonist other than NBI-56418, or 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.
- •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.
Arms & Interventions
Elagolix 150 mg
Participants received 150 mg elagolix orally once a day for 8 weeks during the double-blind treatment period and continued to receive 150 mg elagolix for 16 additional weeks during the open-label treatment period.
Intervention: Elagolix (Drug)
Placebo
Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.
Intervention: Placebo (Drug)
Placebo
Participants received placebo orally once a day for 8 weeks during the double-blind treatment period and switched to receive 150 mg elagolix for 16 weeks during the open-label treatment period.
Intervention: Elagolix (Drug)
Outcomes
Primary Outcomes
Change From Baseline in the Monthly Mean Cumulative Pain Score During the Double-Blind Treatment Phase
Time Frame: Baseline and weeks 4 and 8
Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time each day in an e-Diary according to the following: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) reported during the 4 weeks prior to each visit.
Change From Baseline in the Monthly Mean Cumulative Pain Score During the Open-label and Posttreatment Phases
Time Frame: Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)
Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time each day in an e-Diary according to the following: * 0: No discomfort * 1: Mild discomfort, I was easily able to do the things I usually do * 2: Moderate discomfort or pain making it difficult to do some of the things I usually do * 3: Severe pain making it difficult to do the things I usually do The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.
Change From Baseline in the Monthly Mean Dyspareunia Score During the Double-Blind Treatment Phase
Time Frame: Baseline and weeks 4 and 8
Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: * 0 = Absent; No discomfort during sexual intercourse * 1 = Mild; I was able to tolerate the discomfort during sexual intercourse * 2 = Moderate; Intercourse was interrupted due to pain * 3 = Severe; I avoided intercourse because of pain * Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each visit. Responses of "does not apply" were not included in the calculations.
Change From Baseline in the Monthly Mean Dysmenorrhea Score During the Double-blind Treatment Phase
Time Frame: Baseline and Weeks 4 and 8
Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an electronic diary (e-Diary) according to the following response options: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit.
Change From Baseline in the Monthly Mean Dysmenorrhea Score During the Open-label and Posttreatment Phases
Time Frame: Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)
Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an electronic diary (e-Diary) according to the following response options: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.
Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score During the Open-label and Posttreatment Phases
Time Frame: Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)
Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having their period in an e-Diary according to the following response options: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.
Change From Baseline in the Monthly Mean Dyspareunia Score During the Open-label and Posttreatment Phases
Time Frame: Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment)
Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: * 0: Absent; No discomfort during sexual intercourse * 1: Mild; I was able to tolerate the discomfort during sexual intercourse * 2: Moderate; Intercourse was interrupted due to pain * 3: Severe; I avoided intercourse because of pain * Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each visit, except for week 30 which is based on 6 weeks of data. Responses of "does not apply" were not included in the calculations.
Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score During the Double-Blind Treatment Phase
Time Frame: Baseline and weeks 4 and 8
Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having their period in an e-Diary according to the following response options: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit.
Secondary Outcomes
- Percentage of Participants With a Response in Monthly Mean Non-menstrual Pelvic Pain Score at Week 8(Baseline and Week 8)
- Change From Baseline in the Percentage of Days of Prescription Analgesic Use During the Open-Label and Posttreatment Phases(Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment))
- Change From Baseline in the Percentage of Days of Any Analgesic Use During the Open-Label and Posttreatment Phases(Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment))
- Change From Baseline in the Percentage of Days of Narcotic Analgesic Use During the Open-Label and Posttreatment Phases(Baseline and Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment))
- Patient Global Impression of Change During the Open-Label and Posttreatment Phases(Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment))
- Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved During the Open-label Treatment Phase(Weeks 12, 16, 20, 24, and 30 (6 weeks posttreatment))
- Percentage of Participants With a Response in Monthly Mean Cumulative Pain Score at Week 8(Baseline and Week 8)
- Change From Baseline in the Percentage of Days of Narcotic Analgesic Use During the Double-Blind Treatment Phase(Baseline and Weeks 4 and 8)
- Percentage of Participants With a Response in Monthly Mean Dyspareunia Score at Week 8(Baseline and Week 8)
- Change From Baseline in the Percentage of Days of Prescription Analgesic Use During the Double-Blind Treatment Phase(Baseline and Weeks 4 and 8)
- Change From Baseline to the End of the Open-label Treatment Phase in Endometriosis Health Profile-5 (EHP-5)(Baseline and week 24)
- Percentage of Participants With a Response in Monthly Mean Dysmenorrhea Score at Week 8(Baseline and Week 8)
- Change From Baseline in the Percentage of Days of Any Analgesic Use During the Double-Blind Treatment Phase(Baseline and Weeks 4 and 8)
- Change From Baseline to the End of the Double-blind Treatment Phase in Composite Pelvic Signs and Symptoms Score (CPSSS) Total Score and Component Scores(Baseline and Week 8)
- Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved During the Double-blind Treatment Phase(Weeks 4 and 8)
- Percentage of Days With Uterine Bleeding During the Double- Blind Treatment Phase(Screening (8 weeks prior to day 1) and the double-blind treatment phase (Weeks 1-8))
- Change From Baseline to the End of the Open-label Treatment Phase in Composite Pelvic Signs and Symptoms Score (CPSSS) Total Score and Component Scores(Baseline and week 24)
- Patient Global Impression of Change During the Double-blind Treatment Phase(Weeks 4 and 8)
- Change From Baseline to the End of the Double-blind Treatment Phase in Endometriosis Health Profile-5 (EHP-5)(Baseline and week 8)
- Number of Days to First Posttreatment Menses(From last day of study drug up to 6 weeks after the last dose.)