norethindrone acetate and Fibroid

norethindrone acetate has been researched along with Fibroid in 16 studies

norethisterone acetate : A 3-oxo Delta(4)-steroid that is norethisterone in which the hydroxy group has been converted to its acetate ester.

Research

Studies (16)

Authors

Clinical Trials (14)

Trial Overview

Trial Outcomes

Change From Baseline in MBL Volume to Month 1

(NCT02654054)
Timeframe: Month 0 (Baseline), Month 1

Change From Baseline in MBL Volume to Month 3

(NCT02654054)
Timeframe: Month 0 (Baseline), Month 3

Change From Baseline in MBL Volume to Month 6

(NCT02654054)
Timeframe: Month 0 (Baseline), Month 6

Change From Baseline in MBL Volume to the Final Month

"Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.~The Reference Day 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." (NCT02654054)
Timeframe: Month 0 (Baseline), Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Percentage of Participants Meeting the Criteria for Responder

"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." (NCT02654054)
Timeframe: Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Percentage of Participants With Baseline Hemoglobin <= 10.5 g/dL Who Have an Increase in Hemoglobin > 2 g/dL at Month 6

(NCT02654054)
Timeframe: Month 0 (Baseline), Month 6

Percentage of Participants With Suppression of Bleeding at the Final Month

"Suppression of bleeding is defined as having 0 days of bleeding (spotting is allowed) during the Final Month with the interval starting from Study Day 11.~The Reference Day 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." (NCT02654054)
Timeframe: Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Percentage of Participants Meeting the Criteria for Responder

"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 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." (NCT02925494)
Timeframe: From Month 0 (Baseline in Pivotal Study) to Final Month of Treatment Period (up through Month 6 in Extension Study)

Percentage of Participants With Baseline Hemoglobin Concentration ≤ 10.5 g/dL and an Increase From Baseline > 2 g/dL at Month 6 During the Treatment Period

(NCT02925494)
Timeframe: Month 6

Percentage of Participants With Suppression of Bleeding at the Final Month

Suppression of bleeding is defined as having 0 days of bleeding (spotting is allowed) during the Final Month with the interval starting from Study Day 11. (NCT02925494)
Timeframe: Final Month of Treatment Period (up through Month 6)

Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. (NCT02925494)
Timeframe: Month 0 (Baseline in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through Month 6)

Percent Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. (NCT02925494)
Timeframe: Month 0 (Baseline in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through Month 6)

Change From Baseline to Month 1 in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 mg), the narcotic analgesics 5 mg hydrocodone + 300 or 325 mg acetaminophen, and 30 mg codeine + 300 mg acetaminophen. Assessment was based on average pill counts. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in Health Related Productivity Questionnaire (HRPQ): Number of Hours of Work Lost From Workplace Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in Mean Pain Score of DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in NRS Scores

The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in the Pain Domain of the Endometriosis Health Profile-30 (EHP-30)

The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 1 in the Sexual Intercourse Domain of the EHP-30

The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domian is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Change From Baseline to Month 2 in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 mg), the narcotic analgesics 5 mg hydrocodone + 300 or 325 mg acetaminophen, and 30 mg codeine + 300 mg acetaminophen. Assessment was based on average pill counts. (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in HRPQ: Number of Hours of Work Lost From Workplace Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in Mean Pain Score of DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 2 in NRS Scores

The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Change From Baseline to Month 3 in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 mg), the narcotic analgesics 5 mg hydrocodone + 300 or 325 mg acetaminophen, and 30 mg codeine + 300 mg acetaminophen. Assessment was based on average pill counts. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in Dyspareunia (DYSP)

The DYSP pain scale ranges from 0 (absent) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in HRPQ: Number of Hours of Work Lost From Workplace Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in Numeric Rating Scale (NRS) Scores

The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). (NCT01620528)
Timeframe: Baseline, Month 3 of the Treatment Period

Change From Baseline to Month 3 in the Pain Domain of the EHP-30

The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in the Sexual Intercourse Domain of the EHP-30

The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in Use of Narcotic Class of Medication (Opioids)

Permitted rescue narcotic analgesics included 5 mg hydrocodone + 300 or 325 mg acetaminophen and 30 mg codeine + 300 mg acetaminophen. Assessment was based on average pill counts. (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 4 in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 mg), the narcotic analgesics 5 mg hydrocodone + 300 or 325 mg acetaminophen and 30 mg codeine + 300 mg acetaminophen. Assessment was based on average pill counts. (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in HRPQ: Number of Hours of Work Lost From Workplace Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in Mean Pain Score of DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 4 in NRS Scores

The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Change From Baseline to Month 5 in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 mg), the narcotic analgesics 5 mg hydrocodone + 300 or 325 mg acetaminophen, and 30 mg codeine + 300 mg acetaminophen. Assessment was based on average pill counts. (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in HRPQ: Number of Hours of Work Lost From Workplace Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in Mean Pain Score of DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 5 in NRS Scores

The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Change From Baseline to Month 6 in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 mg), the narcotic analgesics 5 mg hydrocodone + 300 or 325 mg acetaminophen and 30 mg codeine + 300 mg acetaminophen. Assessment was based on average pill counts. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in HRPQ: Number of Hours of Work Lost From Workplace Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in Mean Pain Score of DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in NRS Scores

The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in the Pain Domain of the EHP-30

The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domian is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in the Sexual Intercourse Domain of the EHP-30

The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domian is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Number of Days of Hospitalization

(NCT01620528)
Timeframe: Up to Month 6 of Treatment Period

Percent Change From Baseline to Month 1 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Percent Change From Baseline to Month 1 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 1 of Treatment Period

Percent Change From Baseline to Month 2 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Percent Change From Baseline to Month 2 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 2 of Treatment Period

Percent Change From Baseline to Month 3 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Percent Change From Baseline to Month 3 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 3 of Treatment Period

Percent Change From Baseline to Month 4 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Percent Change From Baseline to Month 4 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 4 of Treatment Period

Percent Change From Baseline to Month 5 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Percent Change From Baseline to Month 5 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 5 of Treatment Period

Percent Change From Baseline to Month 6 in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Percent Change From Baseline to Month 6 in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01620528)
Timeframe: Baseline, Month 6 of Treatment Period

Percentage of Responders at Month 1 Based on Daily Assessment of DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 1 of the Treatment Period

Percentage of Responders at Month 1 Based on Daily Assessment of NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 1 of Treatment Period

Percentage of Responders at Month 1 for DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 1 of the Treatment Period

Percentage of Responders at Month 2 Based on Daily Assessment of DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 2 of the Treatment Period

Percentage of Responders at Month 2 Based on Daily Assessment of NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 2 of Treatment Period

Percentage of Responders at Month 2 for DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 2 of the Treatment Period

Percentage of Responders at Month 3 Based on Daily Assessment of Dysmenorrhea (DYS)

The DYS pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 3 of the Treatment Period

Percentage of Responders at Month 3 Based on Daily Assessment of Non-Menstrual Pelvic Pain (NMPP)

The NMPP pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 3 of Treatment Period

Percentage of Responders at Month 4 Based on Daily Assessment of DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 4 of the Treatment Period

Percentage of Responders at Month 4 Based on Daily Assessment of NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 4 of Treatment Period

Percentage of Responders at Month 4 for DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 4 of the Treatment Period

Percentage of Responders at Month 5 Based on Daily Assessment of DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 5 of the Treatment Period

Percentage of Responders at Month 5 Based on Daily Assessment of NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 5 of Treatment Period

Percentage of Responders at Month 5 for DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 5 of the Treatment Period

Percentage of Responders at Month 6 Based on Daily Assessment of DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 6 of the Treatment Period

Percentage of Responders at Month 6 Based on Daily Assessment of NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 6 of Treatment Period

Percentage of Responders at Month 6 for DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use. (NCT01620528)
Timeframe: At Month 6 of the Treatment Period

Response to Patient Global Impression of Change (PGIC) at Month 1

The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug. (NCT01620528)
Timeframe: Month 1 of Treatment Period

Response to PGIC at Month 2

The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug. (NCT01620528)
Timeframe: Month 2 of Treatment Period

Response to PGIC at Month 3

The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug. (NCT01620528)
Timeframe: Month 3 of Treatment Period

Response to PGIC at Month 4

The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug. (NCT01620528)
Timeframe: Month 4 of Treatment Period

Response to PGIC at Month 5

The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug. (NCT01620528)
Timeframe: Month 5 of Treatment Period

Response to PGIC at Month 6

The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug. (NCT01620528)
Timeframe: Month 6 of Treatment Period

Number of Participants With Emergency Room/Outpatient Procedures During the Treatment Period, by Type

(NCT01620528)
Timeframe: Up to Month 6 of Treatment Period

Number of Participants With Endometriosis-Related Non-Study Health Visits During the Treatment Period

(NCT01620528)
Timeframe: Up to Month 6 of Treatment Period

Change From Baseline to Month 3 in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts. (NCT01931670)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in Dyspareunia (DYSP)

The DYSP pain scale ranges from 0 (absent) to 3 (severe). (NCT01931670)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 3 in Numeric Rating Scale (NRS) Scores

The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). (NCT01931670)
Timeframe: Baseline, Month 3 of the Treatment Period

Change From Baseline to Month 3 in Use of Narcotic Class of Medication (Opioids)

Permitted country-specific rescue narcotic analgesics included 5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen. Assessment was based on average pill counts. (NCT01931670)
Timeframe: Baseline, Month 3 of Treatment Period

Change From Baseline to Month 6 in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts. (NCT01931670)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01931670)
Timeframe: Baseline, Month 6 of Treatment Period

Change From Baseline to Month 6 in NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01931670)
Timeframe: Baseline, Month 6 of Treatment Period

Number of Days of Hospitalization

This is assessed using HRUQ. (NCT01931670)
Timeframe: Up to Month 6 of Treatment Period

Percentage of Responders at Month 3 Based on Daily Assessment of Dysmenorrhea (DYS)

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. (NCT01931670)
Timeframe: At Month 3 of the Treatment Period

Percentage of Responders at Month 3 Based on Daily Assessment of Non-Menstrual Pelvic Pain (NMPP)

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. (NCT01931670)
Timeframe: At Month 3 of Treatment Period

Change From Baseline to Each Month in Health Related Productivity Questionnaire (HRPQ): Number of Hours of Work Lost From Workplace Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration. (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period

Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration. (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period

Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period

Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration. (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period

Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period

Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace

The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration. (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period

Change From Baseline to Each Month, Except Month 3, in NRS Scores

The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever). (NCT01931670)
Timeframe: Baseline, Months 1, 2, 4, 5, 6 of Treatment Period

Change From Baseline to Each Month, Except Month 3, in the Mean Pain Score of DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe). (NCT01931670)
Timeframe: Baseline, Months 1, 2, 4, 5, 6 of Treatment Period

Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01931670)
Timeframe: Baseline (Prior to administering study drug), Months 1, 2, 3, 4, 5 of Treatment Period

Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5 of Treatment Period

Change From Baseline to Each Month, Except Months 3 and 6, in Analgesic Use Across Both Classes of Rescue Analgesics

Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts. (NCT01931670)
Timeframe: Baseline, Months 1, 2, 4, 5

Change From Baseline to Each Scheduled Assessment in the Pain Domain of Endometriosis Health Profile-30 (EHP-30) Questionnaire Scores

The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. (NCT01931670)
Timeframe: Baseline, Months 1, 3, 6 of Treatment Period

Change From Baseline to Each Scheduled Assessment in the Sexual Intercourse Domain of EHP-30 Questionnaire Scores

The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status. (NCT01931670)
Timeframe: Baseline, Months 1, 3, 6 of Treatment Period

Number of Participants With Emergency Room/Outpatient Procedures During the Treatment Period, by Type

This is assessed using HRUQ. (NCT01931670)
Timeframe: Up to Month 6 of Treatment Period

Number of Participants With Endometriosis-Related Non-Study Health Visits During the Treatment Period

This is assessed using Health Resource Utilization Questionnaire (HRUQ). (NCT01931670)
Timeframe: Months 1, 2, 3, 4, 5, 6 of Treatment Period

Patient Global Impression of Change (PGIC) Questionnaire

The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug. (NCT01931670)
Timeframe: Months 1, 2, 3, 4, 5, 6 of Treatment Period

Percent Change From Baseline to Each Month in Mean Pain Score for DYS

The DYS pain scale ranges from 0 (none) to 3 (severe). (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period

Percent Change From Baseline to Each Month in the Mean Pain Score for NMPP

The NMPP pain scale ranges from 0 (none) to 3 (severe). (NCT01931670)
Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period

Percentage of Responders at Each Month for DYSP

The DYSP pain scale ranged from 0 (absent) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.29 or greater from Baseline in DYSP as well as no increased rescue analgesic use for endometriosis-associated pain. (NCT01931670)
Timeframe: Months 1, 2, 3, 4, 5, 6 of Treatment Period

Percentage of Responders for Each Month, Except Month 3, in DYS

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. (NCT01931670)
Timeframe: Months 1, 2, 4, 5, 6 of the Treatment Period

Percentage of Responders for Each Month, Except Month 3, in NMPP

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. (NCT01931670)
Timeframe: Months 1, 2, 4, 5, 6 of the Treatment Period

Change From Baseline in MBL Volume to Month 1

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. (NCT02691494)
Timeframe: Month 0 (Baseline), Month 1

Change From Baseline in MBL Volume to Month 3

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. (NCT02691494)
Timeframe: Month 0 (Baseline), Month 3

Change From Baseline in MBL Volume to Month 6

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. (NCT02691494)
Timeframe: Month 0 (Baseline), Month 6

Change From Baseline in MBL Volume to the Final Month

"Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.~The Reference Day 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." (NCT02691494)
Timeframe: Baseline and Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Percentage of Participants Meeting the Criteria for Responder

"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." (NCT02691494)
Timeframe: Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Percentage of Participants With Baseline Hemoglobin <= 10.5 g/dL Who Have an Increase in Hemoglobin > 2 g/dL at Month 6

(NCT02691494)
Timeframe: Month 0 (Baseline), Month 6

Percentage of Participants With Suppression of Bleeding at the Final Month

"Suppression of bleeding is defined as having 0 days of bleeding (spotting is allowed) during the Final Month with the interval starting from Study Day 11.~The Reference Day 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." (NCT02691494)
Timeframe: Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Number of Days in Hospital During the Treatment Period

The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study, including physician visits, hospitalizations and types of procedures received. (NCT02143713)
Timeframe: 6 months

Number of Participants With Non-study Health Visits During the Treatment Period

The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study. (NCT02143713)
Timeframe: 6 months

Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment

"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." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6

Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment

"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." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6

Change From Baseline in Any Rescue Analgesic Use

Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. Any rescue analgesic use (NSAID and/or opioid) was calculated as the total number of pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day. (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension

"The EHP-30 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-30 consists of two parts: a core questionnaire containing 5 scales that are applicable to all women with endometriosis and includes pain, control and powerlessness, emotional well-being, social support, and self-image, and a modular part containing 6 scales which do not necessarily apply to all women with endometriosis.~Each question in the core questionnaire is scored on the following scale: 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Always.~The pain dimension consists of 11 questions. The dimension score ranges from 0 to 100, where 0 = best possible health status as measured by the questionnaire; 100 = worst possible health status. A negative change from baseline score indicates improvement in quality of life." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 3, and 6

Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension

"The EHP-30 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-30 consists of two parts: a core questionnaire containing 5 scales that are applicable to all women with endometriosis and a modular part containing 6 scales which do not necessarily apply to all women with endometriosis; only 1 modular questionnaire (sexual intercourse [5 items]) was used in this study.~The Sexual Intercourse dimension consists of 5 questions, each answered on the following scale: 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Always, or Not Applicable (not scored). The dimension score ranges from 0 to 100, where 0 = best possible health status as measured by the questionnaire; 100 = worst possible health status. A negative change from baseline score indicates improvement in quality of life." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 3, and 6

Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household

"The HRPQ consists of 9 questions measuring the impact of endometriosis-associated pain and its treatment on work productivity and daily activities in the home.~Absenteeism: Number of hours of intended work lost due to illness or treatment. Presenteeism: Number of hours of work where output was impacted by illness or treatments.~Total hours lost is the sum of hours missed due to absenteeism plus presenteeism." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6

Change From Baseline in NSAID Rescue Analgesic Use

Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. NSAID rescue analgesic use was calculated as the total number of NSAID pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day. (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Change From Baseline in Opioid Rescue Analgesic Use

Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. Opioid rescue analgesic use was calculated as the total number of opioid pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day. (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment

"Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities each day of 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.~Pain scores were averaged over the 35 days prior to each visit." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percent Change From Baseline in Dyspareunia Based on Daily Assessment

"Participants assessed dyspareunia each day in an e-Diary according to the following response options:~0: None; No discomfort during sexual intercourse~1: Mild; Able to tolerate the discomfort during sexual intercourse~2: Moderate; Intercourse was interrupted due to pain~3: Severe; Avoided intercourse because of pain~Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse.~Pain scores were averaged over the 35 days prior to each visit. Responses of Not Applicable were excluded." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS)

The NRS measured endometriosis-associated pain with and without menstruation on an 11-point scale from 0 = no pain to 10 = worst pain ever. Participants were asked to assess their endometriosis pain over the past 24 hours at it's worst at approximately the same time every day in the e-Diary. Pain scores were averaged over the 35 days prior to each visit. (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment

"Participants 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 were averaged over the 35 days prior to each visit." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved

"The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories:~Very Much Improved~Much Improved~Minimally Improved~Not Changed~Minimally Worse~Much Worse~Very Much Worse" (NCT02143713)
Timeframe: Months 1, 2, 3, 4, 5, and 6

Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment

"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." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5

Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment

"Response was defined as a reduction of -0.29 or more from baseline in dyspareunia (pain during sexual intercourse) 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 analgesics).~Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed dyspareunia each day in an e-Diary. Dyspareunia was assessed according to the following:~0: None; No discomfort during sexual intercourse~1: Mild; Able to tolerate the discomfort during sexual intercourse~2: Moderate; Intercourse was interrupted due to pain~3: Severe; Avoided intercourse because of pain~Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse.~Pain scores and analgesic use were averaged over the 35 days prior to each visit. Responses of Not Applicable were excluded." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment

"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." (NCT02143713)
Timeframe: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5

Number of Days in Hospital During the Treatment Period

The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study, including physician visits, hospitalizations and types of procedures received. (NCT01760954)
Timeframe: 6 months

Number of Participants With Non-study Health Visits During the Treatment Period

The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study. (NCT01760954)
Timeframe: 6 months

Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment

"Response was defined as a reduction of -0.81 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 M12-665.~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." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and Month 6

Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment

"Response was defined as a reduction of -0.36 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 M12-665.~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." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and Month 6

Change From Baseline in Any Rescue Analgesic Use

Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, and/or codeine 30 mg + acetaminophen 300 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. Any rescue analgesic use (NSAID and/or opioid) was calculated as the total number of pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day. (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension

"The EHP-30 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-30 consists of two parts: a core questionnaire containing 5 scales that are applicable to all women with endometriosis and includes pain, control and powerlessness, emotional well-being, social support, and self-image, and a modular part containing 6 scales which do not necessarily apply to all women with endometriosis.~Each question in the core questionnaire is scored on the following scale: 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Always.~The pain dimension consists of 11 questions. The dimension score ranges from 0 to 100, where 0 = best possible health status as measured by the questionnaire; 100 = worst possible health status. A negative change from baseline score indicates improvement in quality of life." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 3, and 6

Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension

"The EHP-30 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-30 consists of two parts: a core questionnaire containing 5 scales that are applicable to all women with endometriosis and a modular part containing 6 scales which do not necessarily apply to all women with endometriosis; only 1 modular questionnaire (sexual intercourse [5 items]) was used in this study.~The Sexual Intercourse dimension consists of 5 questions, each answered on the following scale: 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Always, or Not Applicable (not scored). The dimension score ranges from 0 to 100, where 0 = best possible health status as measured by the questionnaire; 100 = worst possible health status. A negative change from baseline score indicates improvement in quality of life." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 3, and 6

Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household

"The HRPQ consists of 9 questions measuring the impact of endometriosis-associated pain and its treatment on work productivity and daily activities in the home.~Absenteeism: Number of hours of intended work lost due to illness or treatment. Presenteeism: Number of hours of work where output was impacted by illness or treatments.~Total hours lost is the sum of hours missed due to absenteeism plus presenteeism." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and month 6

Change From Baseline in NSAID Rescue Analgesic Use

Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, and/or codeine 30 mg + acetaminophen 300 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. NSAID rescue analgesic use was calculated as the total number of NSAID pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day. (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Change From Baseline in Opioid Rescue Analgesic Use

Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, and/or codeine 30 mg + acetaminophen 300 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. Opioid rescue analgesic use was calculated as the total number of opioid pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day. (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment

"Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities each day of 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.~Pain scores were averaged over the 35 days prior to each visit." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percent Change From Baseline in Dyspareunia Based on Daily Assessment

"Participants assessed dyspareunia each day in an e-Diary according to the following response options:~0: None; No discomfort during sexual intercourse~1: Mild; Able to tolerate the discomfort during sexual intercourse~2: Moderate; Intercourse was interrupted due to pain~3: Severe; Avoided intercourse because of pain~Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse.~Pain scores were averaged over the 35 days prior to each visit. Responses of Not Applicable were excluded." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS)

The NRS measured endometriosis-associated pain with and without menstruation on an 11-point scale from 0 = no pain to 10 = worst pain ever. Participants were asked to assess their endometriosis pain over the past 24 hours at it's worst at approximately the same time every day in the e-Diary. Pain scores were averaged over the 35 days prior to each visit. (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment

"Participants 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 were averaged over the 35 days prior to each visit." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved

"The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories:~Very Much Improved~Much Improved~Minimally Improved~Not Changed~Minimally Worse~Much Worse~Very Much Worse" (NCT01760954)
Timeframe: Months 1, 2, 3, 4, 5, and 6

Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment

"Response was defined as a reduction of -0.81 or more from baseline in dysmenorrhea 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 analgesic). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-665.~Participants recorded rescue analgesic medication for endometriosis-associated pain daily and dysmenorrhea (pain during menstruation) and its impact on their daily activities each day of their period in an 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." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5

Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment

"Response was defined as a reduction of -0.36 or more from baseline in dyspareunia (pain during sexual intercourse) 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 analgesics).~Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed dyspareunia each day in an e-Diary. Dyspareunia was assessed according to the following:~0: None; No discomfort during sexual intercourse~1: Mild; Able to tolerate the discomfort during sexual intercourse~2: Moderate; Intercourse was interrupted due to pain~3: Severe; Avoided intercourse because of pain~Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse.~Pain scores and analgesic use were averaged over the 35 days prior to each visit. Responses of Not Applicable were excluded." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment

"Response was defined as a reduction of -0.36 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 M12-665.~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." (NCT01760954)
Timeframe: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5

Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire

"PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group

"Blood samples for determination of E2 serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire

"PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities

"The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities

"The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Higher scores are indicative of better health-related quality of life (high score = good).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score

"Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time and all of the time). Higher scores are indicative of better health-related quality of life (high score = good). LS means and p-value for test of difference was relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of time, most of the time and all of the time.) Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)

"The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Bleeding and Pelvic Discomfort (BPD) Scale has been derived from the UFS-QoL Symptoms Scale. The scale consists of the following 3 symptoms proximal to uterine fibroids: Heavy bleeding during your menstrual period (Question [Q] 1), passing blood clots during your menstrual period (Q2), and feeling tightness or pressure in your pelvic area (Q5), raw scores were transformed to a normalized score: Transformed Score = [(Actual raw score - lowest possible raw score)/(Possible raw score range)]*100 Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates symptom severity.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms" (NCT03103087)
Timeframe: Baseline Week 24

Change From Baseline In E2 Serum Concentration At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline In Follicle Stimulating Serum Concentration At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline In Luteinizing Serum Concentration At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline In Progesterone Serum Concentration At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline in UFS-QoL Bleeding and Pelvic Discomfort Scale Score

"The Bleeding and Pelvic Discomfort Scale consists of 3 items proximal to uterine fibroids that are experienced by most participants (heavy bleeding during the menstrual period [Question 1], passing blood clots during the menstrual period [Question 2], and feeling tightness or pressure in the pelvic area [Question 5]).Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Change From Baseline In UFS-QoL Score by Health-Related Quality of Life Total Score

"The UFS-QoL total score was the sum of 6 subscales (concern, activities, energy/mood, control, self-conscious, and sexual function). The raw scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Number Of Participants Who Achieved A Maximum NRS Score ≤ 1 For Uterine Fibroid-associated Pain Over The Last 35 Days Of Treatment Who Had Maximum Pain Scores ≥ 4 During The 35 Days Prior To Randomization

"Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to the last 35 days of treatment (up to 24 weeks)

Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline

"Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: From Baseline through Week 24

Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: Week 24

Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score

"Responder was defined as meeting a meaningful change threshold, set as a 20-point change from Baseline, in the Bleeding And Pelvic Discomfort Scale at Week 24 on the transformed score.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: From Baseline through Week 24

Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 to L4) As Assessed By DXA

"Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (L1, L2, L3, and L4) at Baseline and at Week 12. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to Week 12

Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03103087)
Timeframe: Baseline, Week 24

Percent Change From Baseline At Week 24 In MBL Volume

"MBL volume was measured using the alkaline hematin method. Least square (LS) means for test of difference is Relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline, Week 24

Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume

"The volume of the primary uterine fibroid was measured by transvaginal or transabdominal ultrasound.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline Week 24

Percent Change From Baseline At Week 24 In Uterine Volume

"The volume of the uterus was measured by transvaginal or transabdominal ultrasound.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to Week 24

Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12

An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term. Reported confidence interval (CI) based on exact binomial 95% CI (Clopper-Pearson). As per the objective of the study, the secondary analysis compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below. (NCT03103087)
Timeframe: Baseline through Week 12

Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24

"An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term.~Reported percentages based on the total number of participants in each treatment group.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Baseline through Week 24

Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA

"A responder was a participant who had MBL volume of < 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 24). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 24/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented.~As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to the last 35 days of treatment (up to Week 24)

Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24

"Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin ≤ 10.5 gram (g)/deciliter (dL) at Baseline and reported at Week 24.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA with placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to Week 24

Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment

"Uterine fibroid-associated pain was assessed by a pain numerical rating scale (NRS). The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~Participants were asked to document, in an e-Diary, the worst pain associated with their uterine fibroids that they experienced during the last 24 hours, every day until the end of study drug administration. Pain evaluable participants, defined as those who had maximum NRS score ≥ 4 at baseline and had at least 28 days (80% of the last 35 days of treatment) of pain scores recorded in the e-Diary, were analyzed.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to Week 24

Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment

"Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits:~No feminine product returned due to reported amenorrhea;~No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (e-Diary) data indicating infrequent non-cyclic bleeding/spotting;~Feminine product collection with a negligible observed MBL volume coupled with e-Diary data indicating infrequent non-cyclic bleeding/spotting.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline up to last 35 days of treatment (up to Week 24)

Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24

"Blood samples for determination of relugolix and NET plasma concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03103087)
Timeframe: Week 24

Sustained Amenorrhea Rate (No Or Negligible Bleeding)

"Sustained amenorrhea is defined as participants time to achieve and maintain amenorrhea until the date of last study drug.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: Week 24

Time To Achieving Amenorrhea (No Or Negligible Bleeding)

"Time to amenorrhea was defined as the weeks from date of first dose of study drug to the start of amenorrhea.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)

"Sustained amenorrhea status as determined based on time to achieve and maintain amenorrhea status.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Time To MBL Response

"Defined as the time to achieve an MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Participants Achieving Improvement From Baseline In PGA For Uterine Fibroid-related Function From Baseline At Week 24

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at Baseline to moderate.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Participants Achieving Improvement From Baseline In PGA Questionnaire For Symptoms From Baseline At Week 24

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03103087)
Timeframe: From Baseline through Week 24

Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck As Assessed By DXA

"BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck (same leg across participants) at Baseline and at Week 24. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects. For Relugolix plus E2/NETA Lumbar Spine (L1 to L4), number (n)=95.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only rel" (NCT03103087)
Timeframe: Baseline through Week 24

Predose Trough Concentrations Of Relugolix And NET In The Relugolix Plus E2/NETA Group At Week 24

"Blood samples for determination of relugolix and NET plasma concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03103087)
Timeframe: Week 24

Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Predose Concentrations Of Estradiol In The Relugolix Plus E2/NETA Group

"Blood samples for determination of serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities

"The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities

"The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score

"Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score

"Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)

"The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Bleeding and Pelvic Discomfort (BPD) Scale has been derived from the UFS-QoL Symptoms Scale. The scale consists of the following 3 symptoms proximal to uterine fibroids: Heavy bleeding during your menstrual period (Question [Q] 1), passing blood clots during your menstrual period (Q2), and feeling tightness or pressure in your pelvic area (Q5). raw scores were transformed to a normalized score: Transformed Score = [(Actual raw score - lowest possible raw score)/(Possible raw score range)] * 100 Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity.~As per the study objective, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only these two arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline In E2 Serum Concentration At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline In Follicle Stimulating Serum Concentration At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline In Luteinizing Serum Concentration At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline In Progesterone Serum Concentration At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline In UFS-QoL Bleeding And Pelvic Discomfort Scale Score

"The Bleeding and Pelvic Discomfort Scale consists of 3 items proximal to uterine fibroids that are experienced by most patients (heavy bleeding during the menstrual period [Question 1], passing blood clots during the menstrual period [Question 2], and feeling tightness or pressure in the pelvic area [Question 5]).Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Change From Baseline In UFS-QoL Score By Health-Related Quality Of Life Total Score

"The UFS-QoL total score was the sum of 6 subscales (concern, activities, energy/mood, control, self-conscious, and sexual function). The raw scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Number Of Participants Who Achieved A Maximum NRS Score ≤ 1 For Uterine Fibroid-associated Pain Over The Last 35 Days Of Treatment Who Had Maximum Pain Scores ≥ 4 During The 35 Days Prior To Randomization

"Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to the last 35 days of treatment (up to 24 weeks)

Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline

"Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: From Baseline through Week 24

Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: Week 24

Number Of Responders With At Least 20 Points Decrease In UFS-QoL Bleeding And Pelvic Discomfort Scale Score

"A Responder was defined as meeting a meaningful change threshold, set as a 20-point change from Baseline, in the Bleeding And Pelvic Discomfort Scale at Week 24 on the transformed score.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: From Baseline through Week 24

Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 To L4), As Assessed By DXA

"Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (L1, L2, L3, and L4) at Baseline and at Week 12. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD.~As per the objective of the study, the pre-specified secondary analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below." (NCT03049735)
Timeframe: Baseline, Week 12

Percent Change From Baseline At Week 24 In MBL Volume

MBL volume was measured using the alkaline hematin method. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented. (NCT03049735)
Timeframe: Baseline, Week 24

Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume

"The volume of the primary uterine fibroid was measured by transvaginal or transabdominal ultrasound.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Percent Change From Baseline At Week 24 In Uterine Volume

"The volume of the uterus was measured by transvaginal or transabdominal ultrasound.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Percent Change From Baseline In Hemoglobin For Women With a Hemoglobin ≤ 10.5 g/dL At Baseline

"LS means and p-value for test of difference is relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Week 24

Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12

"An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term.~Reported CI based on exact binomial 95% CI (Clopper-Pearson).~As per the objective of the study, this secondary analysis compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below." (NCT03049735)
Timeframe: Baseline through Week 12

Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24

"An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term.~Reported percentages based on the total number of participants in each treatment group.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline through Week 24

Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA

"A responder was a participant who had MBL volume of < 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 24). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 24/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented.~As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to last 35 days of treatment (up to Week 24)

Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24

"Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin ≤ 10.5 gram (g)/deciliter (dL) at Baseline and reported at Week 24.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA with placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to Week 24

Percentage Of Participants With A Maximum NRS Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment

"Uterine fibroid-associated pain was assessed by a pain numerical rating scale (NRS). The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).~Participants were asked to document, in an e-Diary, the worst pain associated with their uterine fibroids that they experienced during the last 24 hours, every day until the end of study drug administration. Pain evaluable participants, defined as those who had maximum NRS score ≥ 4 at Baseline and had at least 28 days (80% of the last 35 days of treatment) of pain scores recorded in the e-Diary, were analyzed.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to Week 24

Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment

"Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits:~No feminine product returned due to reported amenorrhea;~No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (eDiary) data indicating infrequent non-cyclic bleeding/spotting;~Feminine product collection with a negligible observed MBL volume coupled with eDiary data indicating infrequent non-cyclic bleeding/spotting.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline up to last 35 days of treatment (up to Week 24)

Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24

"Blood samples for determination of E2 serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03049735)
Timeframe: Week 24

Sustained Amenorrhea Rate (No Or Negligible Bleeding)

"Sustained amenorrhea is defined as participants time to achieve and maintain amenorrhea until the date of last study drug.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Week 24

Time To Achieving Amenorrhea (No Or Negligible Bleeding)

"Time to amenorrhea was defined as the weeks from date of first dose of study drug to the start of amenorrhea.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline through Week 24

Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)

"Sustained amenorrhea status as determined based on time to achieve and maintain amenorrhea status.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline through Week 24

Time To MBL Response

"Defined as the time to achieve an MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method. MBL volume was measured using the alkaline hematin method.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline through Week 24

Participants Achieving Improvement From Baseline In The PGA Questionnaire For Symptoms From Baseline At Week 24

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline through Week 24

Participants Achieving Improvement From Baseline In The PGA Questionnaire For Uterine Fibroid-related Function From Baseline At Week 24

"The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: From Baseline through Week 24

Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck

"BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck at Baseline and at Week 24. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD.~As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented." (NCT03049735)
Timeframe: Baseline, Week 24

Predose Trough Concentrations Of Relugolix And Norethindrone (NET) In The Relugolix Plus E2/NETA Group At Week 24

"Blood samples for determination of relugolix and NET plasma concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.~Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics.~As per the objective of the study, only relugolix plus E2/NETA concentration is presented." (NCT03049735)
Timeframe: Week 24

Change in Bleeding Severity Scores From Baseline at the Final Month

The average bleeding score was calculated for each 28-day interval starting on Day 29 using data collected on daily bleeding diary using the Mansfield-Voda-Jorgenson (MVJ) Menstrual Bleeding Scale (1=spotting, 2 = very light bleeding, 3 = light bleeding, 4 = moderate bleeding, 5 = heavy bleeding, 6 = very heavy/gushing bleeding). Baseline is defined as the last 28 days prior to the first day of study drug. (NCT01817530)
Timeframe: Baseline, Final Month (last 28 days of treatment)

Mean Change in Hemoglobin Concentration From Baseline to Final Visit

Baseline is defined as the last measurement prior to the first dose of study drug. (NCT01817530)
Timeframe: Baseline, Final Visit during treatment period (Month 6 or early termination)

Mean Change in the Number of Bleeding Days From Baseline to Month 6

The number of days with any bleeding including spotting was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug. (NCT01817530)
Timeframe: Baseline, Month 6

Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6

The number of days with heavy bleeding (either heavy or very heavy/gushing bleeding) was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug. (NCT01817530)
Timeframe: Baseline, Month 6

Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment

Amenorrhea is defined as having 0 days of bleeding or spotting based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding or spotting, based on imputed electronic diary data during the last 56 days of treatment. Participants needed to have at least 66 days on treatment. (NCT01817530)
Timeframe: Last 56 days of treatment (after 10 days from first dose date)

Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month

Percentage of participants who achieved an MBL volume of < 80 mL at the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Final Month (last 28 days of treatment)

Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment

Suppression of bleeding is defined as having 0 days of bleeding based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding (spotting is allowed) based on imputed electronic diary data during the last 56 days of treatment. (NCT01817530)
Timeframe: Last 56 days of treatment (after 10 days from first dose date)

Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month

Percentage of participants with a >= 50% reduction from baseline in MBL to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Baseline, Final Month (last 28 days of treatment)

Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment

The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 56 to 29 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Baseline, second last 28 days of treatment (last 56 to 29 days of treatment)

Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment

The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 84 to 57 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period. (NCT01817530)
Timeframe: Baseline, third last 28 days of treatment (last 84 to 57 days of treatment)

Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month

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. (NCT01817530)
Timeframe: Baseline, Final Month (last 28 days of treatment)

Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire

The NBUFSQ (8 items) is a brief patient-reported daily diary that assesses non-bleeding symptoms experienced by women with uterine fibroids. It includes 6 items, asking women to rate their symptoms (abdominal/pelvic pain, pressure, and cramping, back pain, bloating, and urinary problems) in the past 24 hours using an 11-point numeric response scale that ranges from 0 (i.e., no symptom) to 10 (i.e., worst possible symptom) and 2 items to address urinary frequency during the daytime and at night. Data presented in the sum of scores to the 6 symptom questions, ranging from 0 (no symptoms) to 60 (worst possible symptoms). Baseline is defined as the last 28 days prior to the first day of study drug. Final Month is defined as the last 28 days prior to and including the last dose date of study drug. (NCT01817530)
Timeframe: Baseline, Days 1-28, Days 29-56, Days 57-84, Days 85-112, Days 113-140, Days 141-168, Final Month of treatment, Post-treatment (PT) Days 1-28, PT Days 29-56, PT Days 57-84, PT Days 85-112, PT Days 113-140, PT Days 141-168

Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Volume of the largest fibroid (primary fibroid), as measured by transvaginal ultrasound, or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Volume of the total fibroid volume (3 largest fibroids), as measured by transvaginal ultrasound, or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Uterine volume, as measured by transvaginal ultrasound or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)

Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Volume of the largest fibroid (primary fibroid) was measured by transvaginal ultrasound or transabdominal ultrasound. (NCT01817530)
Timeframe: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)