Elagolix

DYS response is measured by the 4-point Endometriosis Daily Pain Impact Scale (none, mild, moderate, severe) and with stable or decreased analgesic use.

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. AEs during the 12-month DB period were defined as any AEs with onset on/after first dose of study drug during the DB period and no more than 30 days after the last dose of study drug for participants who discontinued early during the DB period, or until the first dose of study drug in the OL period for participants who entered the OL Treatment Period. AEs during the OL period were defined as AEs with onset on/after first dose of study drug during the OL period and no more than 30 days after the last dose of study drug. During the post-treatment follow-up (PTFU) period, adverse events were collected from 30 days post-last dose until end of study. Safety reporting during the PTFU period included AESIs. Other AEs may have also been reported.

Percentage of responders, defined as participants who met the following conditions: * Menstrual blood loss (MBL) volume \< 80 mL during the Final Month (the last 28 days prior to and including the Reference Day, which is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date), and * ≥ 50% reduction in MBL volume from Baseline to the Final Month. Participants who prematurely discontinued study drug due to "lack of efficacy," "requires surgery or invasive intervention for treatment of uterine fibroids," or "adverse events" were considered non-responders regardless of whether she meets the two aforementioned responder criteria or not.

Response was defined as a reduction of -0.85 or more from baseline in dysmenorrhea (pain during menstruation) as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a \< 15% increase in average rescue analgesic pill count and no additional analgesic). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic use for endometriosis-associated pain daily and dysmenorrhea and its impact on daily activities each day of their period in an electronic diary (e-Diary). Dysmenorrhea was assessed according to the following: * 0: No discomfort * 1: Mild discomfort but I was easily able to do the things I usually do * 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3: Severe pain that made it difficult to do the things I usually do. Analgesic use and pain scores were averaged over the 35 days prior to each visit.

Response was defined as a reduction of -0.43 or greater from baseline for non-menstrual pelvic pain as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a \< 15% increase in average pill count of rescue analgesics and no additional analgesics). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed non-menstrual pelvic pain and its impact on their daily activities each day in an e-Diary according to the following response options: * 0: No discomfort * 1: Mild discomfort but I was easily able to do the things I usually do * 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3: Severe pain that made it difficult to do the things I usually do. Pain scores and analgesic use were averaged over the 35 days prior to each visit.

The DYS pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.85 or greater from Baseline in DYS pain as well as no increased rescue analgesic use for endometriosis-associated pain.

The NMPP pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.43 or greater from Baseline in NMPP as well as no increased rescue analgesic use for endometriosis-associated pain.

A participant was considered a menstrual cycle responder if she has at least 2 normal menstrual cycles during the final 4 months of the treatment period. In addition, a participant was considered a complete menstrual cycle responder if she has normal menstrual cycles beginning at or before Month 3 that are maintained through Month 6 during the treatment period.

The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL Volume of \< 80 mL at the Final Month and a ≥50% Reduction in MBL Volume from Baseline to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.

The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.

Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an electronic diary (e-Diary) according to the following response options: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit.

Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an electronic diary (e-Diary) according to the following response options: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.

Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having their period in an e-Diary according to the following response options: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit.

Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time each day they were not having their period in an e-Diary according to the following response options: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.

Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time each day in an e-Diary according to the following: * 0 = No discomfort * 1 = Mild discomfort but I was easily able to do the things I usually do * 2 = Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3 = Severe pain that made it difficult to do the things I usually do. The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) reported during the 4 weeks prior to each visit.

Participants assessed dysmenorrhea or non-menstrual pelvic pain at approximately the same time each day in an e-Diary according to the following: * 0: No discomfort * 1: Mild discomfort, I was easily able to do the things I usually do * 2: Moderate discomfort or pain making it difficult to do some of the things I usually do * 3: Severe pain making it difficult to do the things I usually do The monthly mean cumulative pain score is the average of the daily values for all days (menstrual and non-menstrual) reported during the 4 weeks prior to each visit, except for the week 30 value which is based on 6 weeks of data.

Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: * 0 = Absent; No discomfort during sexual intercourse * 1 = Mild; I was able to tolerate the discomfort during sexual intercourse * 2 = Moderate; Intercourse was interrupted due to pain * 3 = Severe; I avoided intercourse because of pain * Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each visit. Responses of "does not apply" were not included in the calculations.

Participants assessed their dyspareunia (pain during sexual intercourse) at approximately the same time every day in an e-Diary according to the following response options: * 0: Absent; No discomfort during sexual intercourse * 1: Mild; I was able to tolerate the discomfort during sexual intercourse * 2: Moderate; Intercourse was interrupted due to pain * 3: Severe; I avoided intercourse because of pain * Does not apply; I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse The monthly mean dyspareunia score is the average of the daily values reported during the 4 weeks prior to each visit, except for week 30 which is based on 6 weeks of data. Responses of "does not apply" were not included in the calculations.

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.

Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in spine and femur BMD at week 24 was assessed using a one-way analysis of variance (ANOVA) model. The absence of significant bone loss was supported if the lower bounds of the confidence intervals for the mean percent change in BMD were ≥ -2.2% for both the spine and femur at week 24.

Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in spine and femur BMD at week 24 was assessed using a one-way analysis of variance (ANOVA) model. The absence of significant bone loss was supported if the lower bounds of the confidence intervals for the mean percent change in BMD were ≥ -2.2% for both the spine and femur at week 24.

Presence or absence of ovulation

As measured by the Hoogland and Skouby 6-point ovarian activity grading system

Implantation rates of both groups will be compared (defined as number of intrauterine gestational sacs with visible cardiac activity noted on ultrasound examination performed 2-3 weeks after initial positive pregnancy test)