Endometriosis
Conditions
Keywords
bone mineral density,endometriosis,pelvic pain
Brief summary
This study is designed to evaluate the safety and beneficial effects of elagolix (NBI-56418) compared to placebo and leuprorelin (an approved endometriosis therapy) over a three month period followed by an additional three months of treatment on elagolix.
Detailed description
The study followed a parallel-group design in which participants were randomized (1:1:1:1) to one of the following treatment groups for the first 12 weeks of dosing: 150 mg elagolix once daily (q.d.); 250 mg elagolix q.d.; placebo; or leuprorelin acetate depot injection 3.75 mg (monthly). Blinding was achieved using a double-dummy design. Following 12 weeks of dosing, participants continued in the study for an additional 12 weeks; participants randomized to elagolix continued to receive their assigned dose and participants randomized to placebo or leuprorelin acetate were re-randomized to receive one of the two doses of elagolix (150 mg q.d. or 250 mg q.d.) for 12 weeks in a double-blind fashion. Six weeks after the last dose of the study drug at the end of Week 24, a follow-up visit was performed (end of Week 30). There was no pre-specified primary efficacy end point as there was no single key efficacy outcome measure in this exploratory Phase 2 study. For purposes of results reported here, Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain is designated as the primary outcome measure.
Interventions
DRUGLeuprorelin Acetate Depot
Leuprorelin acetate depot injection 3.75 mg administered as an intramuscular injection
DRUGElagolix
Elagolix tablets administered orally
Placebo tablet administered orally
DRUGPlacebo to Leuprorelin Acetate
Saline solution administered as an intramuscular injection
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Female, aged 18 to 45 years, inclusive * Have moderate to severe pelvic pain due to endometriosis * Have been surgically (laparoscopy) diagnosed with endometriosis within the last 5 years and have recurrent or persistent endometriosis symptoms * Have regular menstrual cycle (23-33 day) * Agree to use two forms of non-hormonal contraception during the study
Exclusion criteria
* Received a Gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening. * Received subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular (i.m.) medroxyprogesterone acetate (DMPA-IM), or have received either 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 * Are using systemic steroids on a chronic or regular basis within 3 months * Have uterine fibroids or other pelvic lesions ≥ 3 cm in diameter * Have had a hysterectomy or oophorectomy * Have pelvic pain that is not caused by endometriosis * Have unstable medical condition or chronic disease * Have been pregnant within the last 6 months and is currently breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Baseline and Weeks 4, 8, and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Baseline and Weeks 4, 8, and 12 | 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. |
| Change From Baseline in the Monthly Mean Dysmenorrhea Score | Baseline and Weeks 4, 8, and 12 | 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 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. |
| Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Baseline and Weeks 4, 8, and 12 | 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 dysmenorrhea scale included an option for participants who were not having their period. 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. |
| Change From Baseline in the Percentage of Days of Any Analgesic Use | Baseline, Weeks 4, 8 and 12 | 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). |
| Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Baseline, Weeks 4, 8 and 12 | 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). |
| Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Baseline, Weeks 4, 8 and 12 | 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). |
| Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Baseline and Weeks 4, 8, and 12 | 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. |
| Change From Baseline in Dysmenorrhea Component of the CPSSS | Baseline and Week 12 | The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess dysmenorrhea (pain during menstruation), participants were asked to select the best description of painful menstruation over the past 28 days using the following response categories: * 0 = Absent; Amenorrhea (no bleeding) or no discomfort. * 1 = Mild; Some loss of work efficiency; occasional use of analgesics. * 2 = Moderate; In bed part of one day, occasional loss of work; regular use of analgesics. * 3 = Severe; In bed ≥ 1 day, incapacitation; requirement for strong analgesics. |
| Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component | Baseline and Week 12 | The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess non-menstrual pelvic pain, participants were asked to select the best description of pelvic pain over the past 28 days using the following response categories: * 0 = Absent; No discomfort. * 1 = Mild; Occasional pelvic discomfort that can be treated with NSAIDs. * 2 = Moderate; Noticeable discomfort or pain for most of cycle requiring regular use of NSAID or weak opiate. * 3 = Severe; Pain persisting during the cycle or pain requiring strong analgesics. |
| Patient Global Impression of Change at Weeks 4, 8 and 12 | 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: 1. Very Much Improved 2. Much Improved 3. Minimally Improved 4. Not Changed 5. Minimally Worse 6. Much Worse 7. Very Much Worse |
| Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Weeks 4, 8 and 12 | The 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: 1. Very Much Improved 2. Much Improved 3. Minimally Improved 4. Not Changed 5. Minimally Worse 6. Much Worse 7. Very Much Worse |
| Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Baseline and Weeks 4, 8, and 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 peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit. |
| Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Baseline and 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. |
| Concentration of Serum Estradiol | Baseline and Weeks 4, 8 and 12 | The concentration of serum estradiol (E2) was quantified using liquid chromatography with tandem mass spectrophotometry (LC/MS/MS). Serum estradiol concentrations below the limit of quantification (BLQ) were set equal to the lower limit of quantification (2.5 pg/mL). |
| Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12 | Baseline and week 12 | Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA). |
| Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12 | Baseline and week 12 | Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA). |
| Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 | Baseline and Week 24 | Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA). |
| Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 | Baseline and Week 24 | Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA). |
| Change From Baseline in Serum N-telopeptide Concentration at Week 12 | Baseline and week 12 | Blood samples to determine N-telopeptide concentrations were analyzed by a central laboratory using an enzyme-linked immunosorbent assay (ELISA). |
| Average Number of Hot Flashes Per Day | Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups) | Hot flashes, if any, were reported daily by participants during the study using the e-Diary. The average number of hot flashes per day was calculated for each participant as the total number of hot flashes divided by total days in the phase. |
| Percentage of Days With Uterine Bleeding | Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups) | Uterine bleeding was reported daily by participants during the study using the e-Diary. The percentage of days a participant reported any bleeding was calculated as the total number of days the participant reported any bleeding ( light, moderate, or heavy) divided by the total number of days the participant had a non-missing eDiary report of vaginal bleeding in the phase. |
| Number of Days to First Posttreatment Menses | From last day of study drug up to 6 weeks after the last dose. | Defined as the number of days from the last dose of study drug until the start date of the first post-treatment menses. |
| Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Weeks 4, 8 and 12 | The 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: 1. Very Much Improved 2. Much Improved 3. Minimally Improved 4. Not Changed 5. Minimally Worse 6. Much Worse 7. Very Much Worse |
Participant flow
Recruitment details
The study was conducted from 26 November 2008 to 24 February 2010 at 27 centers in Central Eastern Europe (Bulgaria, Hungary, Poland, Romania, Russia and Ukraine).
Pre-assignment details
Patients were randomized equally to oral elagolix 150 mg or 250 mg once daily, placebo or leuprorelin acetate (LA) 1-month depot 3.75 mg injection for 12 weeks. Thereafter, patients originally randomized to placebo or LA were re-randomized to 1 of the elagolix doses and patients randomized to elagolix continued their assigned dose for 12 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo tablets once a day and placebo intramuscular injection once a month 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) for 12 weeks. | 43 |
| Elagolix 150 mg Participants received elagolix 150 mg tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 150 mg for an additional 12 weeks. | 43 |
| Elagolix 250 mg Participants received elagolix 250 mg tablets once a day and placebo intramuscular injection once a month for 12 weeks. At the end of 12 weeks participants continued to receive elagolix 250 mg for an additional 12 weeks. | 44 |
| Leuprorelin Participants received placebo tablets once a day and leuprorelin acetate 1-month depot 3.75 mg intramuscular injection once a month 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) for 12 weeks. | 44 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Weeks 13 to 24 | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| Weeks 13 to 24 | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Weeks 13 to 24 | Non-compliance | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Weeks 13 to 24 | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Weeks 13 to 24 | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Weeks 1 to 12 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Weeks 1 to 12 | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Weeks 1 to 12 | Non-compliance | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Weeks 1 to 12 | Sponsor Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Elagolix 150 mg | Elagolix 250 mg | Leuprorelin | Total |
|---|---|---|---|---|---|
| Age, Continuous | 31.4 years STANDARD_DEVIATION 0.8 | 32.1 years STANDARD_DEVIATION 0.9 | 31.7 years STANDARD_DEVIATION 1 | 31.4 years STANDARD_DEVIATION 0.7 | 31.7 years STANDARD_DEVIATION 0.4 |
| Race/Ethnicity, Customized White | 43 Participants | 43 Participants | 44 Participants | 44 Participants | 174 Participants |
| Sex: Female, Male Female | 43 Participants | 43 Participants | 44 Participants | 44 Participants | 174 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 85 | 0 / 87 | 0 / 44 |
| other Total, other adverse events | 3 / 43 | 25 / 85 | 21 / 87 | 6 / 44 |
| serious Total, serious adverse events | 0 / 43 | 1 / 85 | 2 / 87 | 0 / 44 |
Outcome results
Primary
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.
Time frame: Baseline and Weeks 4, 8, and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 4 | -0.35 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 12 | -1.22 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 8 | -0.93 units on a scale | Standard Error 0.2 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 4 | -0.84 units on a scale | Standard Error 0.17 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 12 | -1.34 units on a scale | Standard Error 0.21 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 8 | -1.25 units on a scale | Standard Error 0.2 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 8 | -1.57 units on a scale | Standard Error 0.2 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 4 | -1.00 units on a scale | Standard Error 0.17 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 12 | -1.47 units on a scale | Standard Error 0.21 |
| Leuprorelin | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 4 | -0.94 units on a scale | Standard Error 0.17 |
| Leuprorelin | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 12 | -1.81 units on a scale | Standard Error 0.2 |
| Leuprorelin | Change From Baseline in the Monthly Mean Numerical Rating Score (NRS) for Endometriosis Pain | Week 8 | -1.55 units on a scale | Standard Error 0.2 |
Comparison: Analysis at Week 4. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.046495% CI: [-0.98, -0.01]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.00895% CI: [-1.13, -0.17]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.015995% CI: [-1.08, -0.11]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.256395% CI: [-0.89, 0.24]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.023995% CI: [-1.21, -0.09]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.02895% CI: [-1.19, -0.07]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.690495% CI: [-0.7, 0.46]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.402295% CI: [-0.83, 0.33]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean values of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.045195% CI: [-1.17, -0.01]Mixed-effects Repeated Measures Model
Secondary
Average Number of Hot Flashes Per Day
Hot flashes, if any, were reported daily by participants during the study using the e-Diary. The average number of hot flashes per day was calculated for each participant as the total number of hot flashes divided by total days in the phase.
Time frame: Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups)
Population: Participants who received at least one dose of randomized, double-blind study drug (safety analysis set).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Average Number of Hot Flashes Per Day | Treatment Phase | 0.11 hot flashes per day |
| Placebo | Average Number of Hot Flashes Per Day | Screening | 0.00 hot flashes per day |
| Elagolix 150 mg | Average Number of Hot Flashes Per Day | Treatment Phase | 0.22 hot flashes per day |
| Elagolix 150 mg | Average Number of Hot Flashes Per Day | Screening | 0.00 hot flashes per day |
| Elagolix 250 mg | Average Number of Hot Flashes Per Day | Screening | 0.00 hot flashes per day |
| Elagolix 250 mg | Average Number of Hot Flashes Per Day | Treatment Phase | 1.10 hot flashes per day |
| Leuprorelin | Average Number of Hot Flashes Per Day | Treatment Phase | 1.73 hot flashes per day |
| Leuprorelin | Average Number of Hot Flashes Per Day | Screening | 0.00 hot flashes per day |
Secondary
Change From Baseline in Dysmenorrhea Component of the CPSSS
The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess dysmenorrhea (pain during menstruation), participants were asked to select the best description of painful menstruation over the past 28 days using the following response categories: * 0 = Absent; Amenorrhea (no bleeding) or no discomfort. * 1 = Mild; Some loss of work efficiency; occasional use of analgesics. * 2 = Moderate; In bed part of one day, occasional loss of work; regular use of analgesics. * 3 = Severe; In bed ≥ 1 day, incapacitation; requirement for strong analgesics.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). Data collection for this endpoint was added via a protocol amendment; therefore, the analysis only includes the subset of participants affected by the protocol amendment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dysmenorrhea Component of the CPSSS | -1.03 units on a scale | Standard Error 0.17 |
| Elagolix 150 mg | Change From Baseline in Dysmenorrhea Component of the CPSSS | -1.29 units on a scale | Standard Error 0.17 |
| Elagolix 250 mg | Change From Baseline in Dysmenorrhea Component of the CPSSS | -1.47 units on a scale | Standard Error 0.16 |
| Leuprorelin | Change From Baseline in Dysmenorrhea Component of the CPSSS | -1.75 units on a scale | Standard Error 0.15 |
Secondary
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.
Time frame: Baseline and Weeks 4, 8, and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at baseline and at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 4 | -0.33 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 8 | -0.72 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 12 | -0.60 units on a scale | Standard Error 0.11 |
| Elagolix 150 mg | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 4 | -0.46 units on a scale | Standard Error 0.11 |
| Elagolix 150 mg | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 8 | -0.68 units on a scale | Standard Error 0.11 |
| Elagolix 150 mg | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 12 | -0.84 units on a scale | Standard Error 0.12 |
| Elagolix 250 mg | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 12 | -0.89 units on a scale | Standard Error 0.11 |
| Elagolix 250 mg | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 4 | -0.49 units on a scale | Standard Error 0.11 |
| Elagolix 250 mg | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 8 | -0.77 units on a scale | Standard Error 0.11 |
| Leuprorelin | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 8 | -0.76 units on a scale | Standard Error 0.11 |
| Leuprorelin | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 12 | -1.04 units on a scale | Standard Error 0.11 |
| Leuprorelin | Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) | Week 4 | -0.55 units on a scale | Standard Error 0.11 |
Secondary
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.
Time frame: Baseline and week 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data for each dimension at baseline and week 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Sexual Intercourse | -32.2 units on a scale | Standard Error 5.7 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Self-image | -12.2 units on a scale | Standard Error 6.5 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Control and Powerlessness | -18.3 units on a scale | Standard Error 4.4 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Relationship with Children | -11.5 units on a scale | Standard Error 6.7 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Work | -23.7 units on a scale | Standard Error 3.9 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Emotional Wellbeing | -14.6 units on a scale | Standard Error 4.2 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Frustration with Treatment | -11.4 units on a scale | Standard Error 6.1 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Pain | -14.0 units on a scale | Standard Error 4.8 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Concerns with Infertility | -19.7 units on a scale | Standard Error 5 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Medical Profession | -5.3 units on a scale | Standard Error 4.5 |
| Placebo | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Social Support | -22.0 units on a scale | Standard Error 4.4 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Medical Profession | -5.5 units on a scale | Standard Error 4 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Pain | -19.0 units on a scale | Standard Error 4.1 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Control and Powerlessness | -17.9 units on a scale | Standard Error 3.9 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Emotional Wellbeing | -10.7 units on a scale | Standard Error 4.1 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Self-image | -7.7 units on a scale | Standard Error 4.5 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Work | -21.5 units on a scale | Standard Error 4.5 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Relationship with Children | -15.3 units on a scale | Standard Error 5.4 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Sexual Intercourse | -21.2 units on a scale | Standard Error 6.2 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Frustration with Treatment | -10.9 units on a scale | Standard Error 6.3 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Social Support | -16.1 units on a scale | Standard Error 4.4 |
| Elagolix 150 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Concerns with Infertility | -24.0 units on a scale | Standard Error 7 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Social Support | -18.6 units on a scale | Standard Error 5.6 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Sexual Intercourse | -30.6 units on a scale | Standard Error 5.3 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Medical Profession | -7.6 units on a scale | Standard Error 3 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Control and Powerlessness | -20.9 units on a scale | Standard Error 5.1 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Work | -29.9 units on a scale | Standard Error 5.1 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Frustration with Treatment | -7.6 units on a scale | Standard Error 6.9 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Concerns with Infertility | -13.8 units on a scale | Standard Error 5.2 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Pain | -25.0 units on a scale | Standard Error 4.7 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Emotional Wellbeing | -12.8 units on a scale | Standard Error 4.4 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Self-image | -5.8 units on a scale | Standard Error 5 |
| Elagolix 250 mg | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Relationship with Children | -25.0 units on a scale | Standard Error 7.6 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Frustration with Treatment | -12.5 units on a scale | Standard Error 6.9 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Social Support | -15.3 units on a scale | Standard Error 5.1 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Pain | -31.8 units on a scale | Standard Error 3.9 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Sexual Intercourse | -28.9 units on a scale | Standard Error 5.7 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Emotional Wellbeing | -13.6 units on a scale | Standard Error 4.4 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Control and Powerlessness | -23.9 units on a scale | Standard Error 4.9 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Relationship with Children | -22.9 units on a scale | Standard Error 9.5 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Medical Profession | -6.3 units on a scale | Standard Error 4.2 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Concerns with Infertility | -13.3 units on a scale | Standard Error 4.8 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Work | -38.6 units on a scale | Standard Error 4.3 |
| Leuprorelin | Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12 | Self-image | -8.5 units on a scale | Standard Error 4.1 |
Secondary
Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component
The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration. To assess non-menstrual pelvic pain, participants were asked to select the best description of pelvic pain over the past 28 days using the following response categories: * 0 = Absent; No discomfort. * 1 = Mild; Occasional pelvic discomfort that can be treated with NSAIDs. * 2 = Moderate; Noticeable discomfort or pain for most of cycle requiring regular use of NSAID or weak opiate. * 3 = Severe; Pain persisting during the cycle or pain requiring strong analgesics.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). Data collection for this endpoint was added via a protocol amendment; therefore, the analysis only includes the subset of participants affected by the protocol amendment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component | -0.60 units on a scale | Standard Error 0.12 |
| Elagolix 150 mg | Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component | -0.58 units on a scale | Standard Error 0.12 |
| Elagolix 250 mg | Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component | -0.48 units on a scale | Standard Error 0.11 |
| Leuprorelin | Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component | -0.79 units on a scale | Standard Error 0.11 |
Secondary
Change From Baseline in Serum N-telopeptide Concentration at Week 12
Blood samples to determine N-telopeptide concentrations were analyzed by a central laboratory using an enzyme-linked immunosorbent assay (ELISA).
Time frame: Baseline and week 12
Population: Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) and with available data at baseline and week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Serum N-telopeptide Concentration at Week 12 | 0.62 nM bone collagen equivalents (BCE) | Standard Error 0.78 |
| Elagolix 150 mg | Change From Baseline in Serum N-telopeptide Concentration at Week 12 | 0.77 nM bone collagen equivalents (BCE) | Standard Error 0.69 |
| Elagolix 250 mg | Change From Baseline in Serum N-telopeptide Concentration at Week 12 | 2.04 nM bone collagen equivalents (BCE) | Standard Error 0.66 |
| Leuprorelin | Change From Baseline in Serum N-telopeptide Concentration at Week 12 | 3.18 nM bone collagen equivalents (BCE) | Standard Error 0.72 |
Secondary
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 of their period 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.
Time frame: Baseline and Weeks 4, 8, and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 12 | -0.35 units on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 4 | -0.17 units on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 8 | -0.40 units on a scale | Standard Error 0.08 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 12 | -0.76 units on a scale | Standard Error 0.08 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 8 | -0.86 units on a scale | Standard Error 0.08 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 4 | -0.64 units on a scale | Standard Error 0.08 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 4 | -0.67 units on a scale | Standard Error 0.08 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 8 | -1.04 units on a scale | Standard Error 0.08 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 12 | -0.87 units on a scale | Standard Error 0.08 |
| Leuprorelin | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 4 | -0.65 units on a scale | Standard Error 0.08 |
| Leuprorelin | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 12 | -1.14 units on a scale | Standard Error 0.08 |
| Leuprorelin | Change From Baseline in the Monthly Mean Dysmenorrhea Score | Week 8 | -1.22 units on a scale | Standard Error 0.08 |
Comparison: Analysis at Week 4. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.69, -0.24]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.73, -0.27]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.71, -0.25]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.69, -0.23]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.87, -0.4]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-1.04, -0.59]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.000595% CI: [-0.65, -0.18]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.76, -0.29]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean dysmenorrhea scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-1.02, -0.56]Mixed-effects Repeated Measures Model
Secondary
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.
Time frame: Baseline and Weeks 4, 8, and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 4 | -0.05 units on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 12 | -0.30 units on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 8 | -0.18 units on a scale | Standard Error 0.06 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 4 | -0.22 units on a scale | Standard Error 0.06 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 12 | -0.35 units on a scale | Standard Error 0.06 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 8 | -0.34 units on a scale | Standard Error 0.06 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 8 | -0.36 units on a scale | Standard Error 0.06 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 4 | -0.21 units on a scale | Standard Error 0.06 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 12 | -0.34 units on a scale | Standard Error 0.06 |
| Leuprorelin | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 4 | -0.27 units on a scale | Standard Error 0.06 |
| Leuprorelin | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 12 | -0.55 units on a scale | Standard Error 0.06 |
| Leuprorelin | Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score | Week 8 | -0.46 units on a scale | Standard Error 0.06 |
Comparison: Analysis at Week 4. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.045395% CI: [-0.33, 0]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.060995% CI: [-0.31, 0.01]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.006995% CI: [-0.38, -0.06]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.055695% CI: [-0.32, 0]Mixed-effects Repeated Measures Model]
Comparison: Analysis at Week 8. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.038795% CI: [-0.33, -0.01]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.000895% CI: [-0.44, -0.12]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.587995% CI: [-0.21, 0.12]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.612295% CI: [-0.2, 0.12]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.002395% CI: [-0.41, -0.09]Mixed-effects Repeated Measures Model
Secondary
Change From Baseline in the Monthly Mean Sum 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 dysmenorrhea scale included an option for participants who were not having their period. 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.
Time frame: Baseline and Weeks 4, 8, and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 4 | -0.12 units on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 12 | -0.40 units on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 8 | -0.24 units on a scale | Standard Error 0.07 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 4 | -0.43 units on a scale | Standard Error 0.07 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 12 | -0.55 units on a scale | Standard Error 0.07 |
| Elagolix 150 mg | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 8 | -0.58 units on a scale | Standard Error 0.07 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 8 | -0.67 units on a scale | Standard Error 0.07 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 4 | -0.44 units on a scale | Standard Error 0.07 |
| Elagolix 250 mg | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 12 | -0.63 units on a scale | Standard Error 0.07 |
| Leuprorelin | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 4 | -0.50 units on a scale | Standard Error 0.07 |
| Leuprorelin | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 12 | -0.87 units on a scale | Standard Error 0.07 |
| Leuprorelin | Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores | Week 8 | -0.78 units on a scale | Standard Error 0.07 |
Comparison: Analysis at Week 4. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.001195% CI: [-0.51, -0.13]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.00195% CI: [-0.51, -0.13]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.57, -0.19]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.000795% CI: [-0.52, -0.14]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.62, -0.24]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.73, -0.35]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.131995% CI: [-0.34, 0.04]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.022295% CI: [-0.42, -0.03]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-0.66, -0.28]Mixed-effects Repeated Measures Model
Secondary
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.
Time frame: Baseline and Weeks 4, 8, and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 4 | -0.20 units on a scale | Standard Error 0.34 |
| Placebo | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 12 | -1.67 units on a scale | Standard Error 0.34 |
| Placebo | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 8 | -0.89 units on a scale | Standard Error 0.34 |
| Elagolix 150 mg | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 4 | -1.82 units on a scale | Standard Error 0.34 |
| Elagolix 150 mg | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 12 | -2.62 units on a scale | Standard Error 0.34 |
| Elagolix 150 mg | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 8 | -2.23 units on a scale | Standard Error 0.34 |
| Elagolix 250 mg | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 8 | -2.96 units on a scale | Standard Error 0.33 |
| Elagolix 250 mg | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 4 | -1.83 units on a scale | Standard Error 0.33 |
| Elagolix 250 mg | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 12 | -3.05 units on a scale | Standard Error 0.34 |
| Leuprorelin | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 4 | -1.48 units on a scale | Standard Error 0.33 |
| Leuprorelin | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 12 | -3.99 units on a scale | Standard Error 0.33 |
| Leuprorelin | Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain | Week 8 | -3.62 units on a scale | Standard Error 0.33 |
Comparison: Analysis at Week 4. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.000795% CI: [-2.56, -0.69]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.000695% CI: [-2.56, -0.7]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 4. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.007395% CI: [-2.21, -0.35]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.005495% CI: [-2.28, -0.4]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-3.01, -1.12]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 8. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-3.67, -1.79]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.050995% CI: [-1.89, 0]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: 0.004695% CI: [-2.33, -0.43]Mixed-effects Repeated Measures Model
Comparison: Analysis at Week 12. The change from baseline in monthly peak value of the NRS for overall endometriosis-associated pelvic pain was analyzed using a mixed-effects repeated measures analysis of covariance model. The model included fixed effects for treatment, time, the treatment-by-time interaction, a random effect for participant, the baseline-by-time interaction and the baseline value as a covariate.p-value: <0.000195% CI: [-3.26, -1.38]Mixed-effects Repeated Measures Model
Secondary
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).
Time frame: Baseline, Weeks 4, 8 and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 4 | -5.2 percentage of days | Standard Error 2 |
| Placebo | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 12 | -6.2 percentage of days | Standard Error 2 |
| Placebo | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 8 | -6.2 percentage of days | Standard Error 2 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 4 | -1.1 percentage of days | Standard Error 2 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 12 | -4.4 percentage of days | Standard Error 2 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 8 | -3.4 percentage of days | Standard Error 2 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 8 | -9.1 percentage of days | Standard Error 2 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 4 | -8.4 percentage of days | Standard Error 2 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 12 | -8.3 percentage of days | Standard Error 2 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 4 | -8.7 percentage of days | Standard Error 2 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 12 | -10.5 percentage of days | Standard Error 2 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Any Analgesic Use | Week 8 | -10.2 percentage of days | Standard Error 2 |
Secondary
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).
Time frame: Baseline, Weeks 4, 8 and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 4 | 0.0 percentage of days | Standard Error 0.1 |
| Placebo | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 12 | 0.0 percentage of days | Standard Error 0.1 |
| Placebo | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 8 | -0.1 percentage of days | Standard Error 0.1 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 4 | -0.1 percentage of days | Standard Error 0.1 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 12 | 0.1 percentage of days | Standard Error 0.1 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 8 | -0.1 percentage of days | Standard Error 0.1 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 8 | -0.1 percentage of days | Standard Error 0.1 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 4 | 0.0 percentage of days | Standard Error 0.1 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 12 | 0.1 percentage of days | Standard Error 0.1 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 4 | -0.1 percentage of days | Standard Error 0.1 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 12 | 0.3 percentage of days | Standard Error 0.1 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Narcotic Analgesic Use | Week 8 | -0.1 percentage of days | Standard Error 0.1 |
Secondary
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).
Time frame: Baseline, Weeks 4, 8 and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 4 | -0.3 percentage of days | Standard Error 1.8 |
| Placebo | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 12 | -1.8 percentage of days | Standard Error 1.4 |
| Placebo | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 8 | -1.3 percentage of days | Standard Error 1.6 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 4 | 3.4 percentage of days | Standard Error 1.8 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 12 | 0.7 percentage of days | Standard Error 1.4 |
| Elagolix 150 mg | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 8 | 1.3 percentage of days | Standard Error 1.6 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 8 | -2.8 percentage of days | Standard Error 1.6 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 4 | -1.2 percentage of days | Standard Error 1.7 |
| Elagolix 250 mg | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 12 | -1.9 percentage of days | Standard Error 1.4 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 4 | -2.5 percentage of days | Standard Error 1.7 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 12 | -2.8 percentage of days | Standard Error 1.3 |
| Leuprorelin | Change From Baseline in the Percentage of Days of Prescription Analgesic Use | Week 8 | -2.6 percentage of days | Standard Error 1.6 |
Secondary
Concentration of Serum Estradiol
The concentration of serum estradiol (E2) was quantified using liquid chromatography with tandem mass spectrophotometry (LC/MS/MS). Serum estradiol concentrations below the limit of quantification (BLQ) were set equal to the lower limit of quantification (2.5 pg/mL).
Time frame: Baseline and Weeks 4, 8 and 12
Population: Randomized participants who received at least one dose of randomized, double-blind study drug with at least one eDiary value following randomization, excluding participants who had less than 80% oral study drug dosing compliance during Weeks 1-12 (per protocol population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Concentration of Serum Estradiol | Baseline | 39.10 pg/mL |
| Placebo | Concentration of Serum Estradiol | Week 4 | 49.50 pg/mL |
| Placebo | Concentration of Serum Estradiol | Week 8 | 61.00 pg/mL |
| Placebo | Concentration of Serum Estradiol | Week 12 | 87.90 pg/mL |
| Elagolix 150 mg | Concentration of Serum Estradiol | Week 4 | 36.40 pg/mL |
| Elagolix 150 mg | Concentration of Serum Estradiol | Week 8 | 36.90 pg/mL |
| Elagolix 150 mg | Concentration of Serum Estradiol | Week 12 | 36.70 pg/mL |
| Elagolix 150 mg | Concentration of Serum Estradiol | Baseline | 43.40 pg/mL |
| Elagolix 250 mg | Concentration of Serum Estradiol | Week 8 | 23.65 pg/mL |
| Elagolix 250 mg | Concentration of Serum Estradiol | Week 4 | 22.00 pg/mL |
| Elagolix 250 mg | Concentration of Serum Estradiol | Week 12 | 26.20 pg/mL |
| Elagolix 250 mg | Concentration of Serum Estradiol | Baseline | 47.50 pg/mL |
| Leuprorelin | Concentration of Serum Estradiol | Week 12 | 6.38 pg/mL |
| Leuprorelin | Concentration of Serum Estradiol | Week 4 | 3.63 pg/mL |
| Leuprorelin | Concentration of Serum Estradiol | Baseline | 46.20 pg/mL |
| Leuprorelin | Concentration of Serum Estradiol | Week 8 | 4.36 pg/mL |
Secondary
Number of Days to First Posttreatment Menses
Defined as the number of days from the last dose of study drug until the start date of the first post-treatment menses.
Time frame: From last day of study drug up to 6 weeks after the last dose.
Population: Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) with non-missing post-treatment data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Number of Days to First Posttreatment Menses | 22.5 days |
| Elagolix 150 mg | Number of Days to First Posttreatment Menses | 26.0 days |
| Elagolix 250 mg | Number of Days to First Posttreatment Menses | 26.0 days |
| Leuprorelin | Number of Days to First Posttreatment Menses | 27.0 days |
| Leuprorelin / Elagolix 150 mg | Number of Days to First Posttreatment Menses | 29.0 days |
| Leuprorelin / Elagolix 250 mg | Number of Days to First Posttreatment Menses | 28.0 days |
Secondary
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: 1. Very Much Improved 2. Much Improved 3. Minimally Improved 4. Not Changed 5. Minimally Worse 6. Much Worse 7. Very Much Worse
Time frame: Weeks 4, 8 and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 4 | 3.4 units on a scale | Standard Error 0.1 |
| Placebo | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 12 | 2.6 units on a scale | Standard Error 0.2 |
| Placebo | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 8 | 2.8 units on a scale | Standard Error 0.1 |
| Elagolix 150 mg | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 4 | 3.0 units on a scale | Standard Error 0.1 |
| Elagolix 150 mg | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 12 | 2.4 units on a scale | Standard Error 0.1 |
| Elagolix 150 mg | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 8 | 2.5 units on a scale | Standard Error 0.2 |
| Elagolix 250 mg | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 8 | 2.2 units on a scale | Standard Error 0.1 |
| Elagolix 250 mg | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 4 | 2.9 units on a scale | Standard Error 0.2 |
| Elagolix 250 mg | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 12 | 2.2 units on a scale | Standard Error 0.2 |
| Leuprorelin | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 4 | 3.3 units on a scale | Standard Error 0.1 |
| Leuprorelin | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 12 | 2.1 units on a scale | Standard Error 0.1 |
| Leuprorelin | Patient Global Impression of Change at Weeks 4, 8 and 12 | Week 8 | 2.3 units on a scale | Standard Error 0.1 |
Secondary
Percentage of Days With Uterine Bleeding
Uterine bleeding was reported daily by participants during the study using the e-Diary. The percentage of days a participant reported any bleeding was calculated as the total number of days the participant reported any bleeding ( light, moderate, or heavy) divided by the total number of days the participant had a non-missing eDiary report of vaginal bleeding in the phase.
Time frame: Screening (8 weeks prior to day 1), Treatment phase (weeks 1 to 12 for participants in the placebo and leuprorelin treatment groups and weeks 1 to 24 for participants in the elagolix treatment groups)
Population: Participants who received at least one dose of randomized, double-blind study drug (safety analysis set).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage of Days With Uterine Bleeding | Screening | 21.10 percentage of days | Standard Error 1.78 |
| Placebo | Percentage of Days With Uterine Bleeding | Treatment Phase | 21.46 percentage of days | Standard Error 1.39 |
| Elagolix 150 mg | Percentage of Days With Uterine Bleeding | Treatment Phase | 10.78 percentage of days | Standard Error 1.14 |
| Elagolix 150 mg | Percentage of Days With Uterine Bleeding | Screening | 18.32 percentage of days | Standard Error 1.14 |
| Elagolix 250 mg | Percentage of Days With Uterine Bleeding | Screening | 22.32 percentage of days | Standard Error 1.68 |
| Elagolix 250 mg | Percentage of Days With Uterine Bleeding | Treatment Phase | 9.54 percentage of days | Standard Error 1.35 |
| Leuprorelin | Percentage of Days With Uterine Bleeding | Screening | 21.05 percentage of days | Standard Error 1.87 |
| Leuprorelin | Percentage of Days With Uterine Bleeding | Treatment Phase | 11.04 percentage of days | Standard Error 1.3 |
Secondary
Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved
The 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: 1. Very Much Improved 2. Much Improved 3. Minimally Improved 4. Not Changed 5. Minimally Worse 6. Much Worse 7. Very Much Worse
Time frame: Weeks 4, 8 and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 4 | 56.1 percentage of participants |
| Placebo | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 12 | 80.5 percentage of participants |
| Placebo | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 8 | 75.6 percentage of participants |
| Elagolix 150 mg | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 4 | 74.4 percentage of participants |
| Elagolix 150 mg | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 12 | 88.1 percentage of participants |
| Elagolix 150 mg | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 8 | 81.4 percentage of participants |
| Elagolix 250 mg | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 8 | 90.7 percentage of participants |
| Elagolix 250 mg | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 4 | 65.1 percentage of participants |
| Elagolix 250 mg | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 12 | 88.4 percentage of participants |
| Leuprorelin | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 4 | 50.0 percentage of participants |
| Leuprorelin | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 12 | 93.2 percentage of participants |
| Leuprorelin | Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved | Week 8 | 88.6 percentage of participants |
Secondary
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved
The 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: 1. Very Much Improved 2. Much Improved 3. Minimally Improved 4. Not Changed 5. Minimally Worse 6. Much Worse 7. Very Much Worse
Time frame: Weeks 4, 8 and 12
Population: All randomized participants who received at least 1 dose of study drug and had at least 1 evaluable e-Diary report following randomization (intent-to-treat population). The analysis includes participants with non-missing data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 4 | 7.3 percentage of participants |
| Placebo | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 12 | 53.7 percentage of participants |
| Placebo | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 8 | 36.6 percentage of participants |
| Elagolix 150 mg | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 4 | 25.6 percentage of participants |
| Elagolix 150 mg | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 12 | 54.8 percentage of participants |
| Elagolix 150 mg | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 8 | 53.5 percentage of participants |
| Elagolix 250 mg | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 8 | 72.1 percentage of participants |
| Elagolix 250 mg | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 4 | 32.6 percentage of participants |
| Elagolix 250 mg | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 12 | 67.4 percentage of participants |
| Leuprorelin | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 4 | 27.3 percentage of participants |
| Leuprorelin | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 12 | 70.5 percentage of participants |
| Leuprorelin | Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved | Week 8 | 54.5 percentage of participants |
Secondary
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).
Time frame: Baseline and week 12
Population: Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) and with available BMD data at baseline and week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12 | -0.90 percent change | Standard Deviation 1.316 |
| Elagolix 150 mg | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12 | -0.342 percent change | Standard Deviation 1.583 |
| Elagolix 250 mg | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12 | -0.5623 percent change | Standard Deviation 1.367 |
| Leuprorelin | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12 | -1.122 percent change | Standard Deviation 1.634 |
Secondary
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).
Time frame: Baseline and Week 24
Population: Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) and with available BMD data at baseline and week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 | -0.549 percent change | Standard Deviation 1.827 |
| Elagolix 150 mg | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 | -0.699 percent change | Standard Deviation 1.574 |
| Elagolix 250 mg | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 | -0.126 percent change | Standard Deviation 1.732 |
| Leuprorelin | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 | -0.573 percent change | Standard Deviation 1.328 |
| Leuprorelin / Elagolix 150 mg | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 | -1.784 percent change | Standard Deviation 1.571 |
| Leuprorelin / Elagolix 250 mg | Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24 | -1.783 percent change | Standard Deviation 2.096 |
Secondary
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).
Time frame: Baseline and week 12
Population: Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) and with available BMD data at baseline and week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12 | 0.106 percent change | Standard Deviation 1.893 |
| Elagolix 150 mg | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12 | -1.053 percent change | Standard Deviation 1.985 |
| Elagolix 250 mg | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12 | -0.799 percent change | Standard Deviation 2.352 |
| Leuprorelin | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12 | -1.633 percent change | Standard Deviation 2.113 |
Secondary
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).
Time frame: Baseline and Week 24
Population: Participants who received at least one dose of randomized, double-blind study drug (safety analysis set) and with available BMD data at baseline and week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 | -1.288 percent change | Standard Deviation 2.681 |
| Elagolix 150 mg | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 | -1.855 percent change | Standard Deviation 2.67 |
| Elagolix 250 mg | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 | -0.990 percent change | Standard Deviation 2.636 |
| Leuprorelin | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 | -0.648 percent change | Standard Deviation 2.377 |
| Leuprorelin / Elagolix 150 mg | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 | -2.899 percent change | Standard Deviation 2.733 |
| Leuprorelin / Elagolix 250 mg | Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24 | -4.378 percent change | Standard Deviation 2.099 |