Trial Outcomes & Findings for Global Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Women With Moderate to Severe Endometriosis-associated Pain (NCT NCT02143713)

Last Updated: 2021-07-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

496 participants

Primary outcome 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

Results posted on

2021-07-13

Participant Flow

Participants who completed the 6-month Treatment Period in the pivotal Study M12-671 (NCT01931670) could enter this extension study. A total of 96 participants were enrolled at 148 sites in North and South America, Europe, Australia/New Zealand, and South Africa. One enrolled patient did not receive study drug and is not included in these results.

The study consisted of a 6-month Treatment Period and a Post-treatment Follow-up (PTFU) of up to 12 months. Participants who received elagolix in the pivotal study continued to receive the same dose for a further 6 months; participants on placebo in the pivotal study were randomized 1:1 to either elagolix 150 mg once daily or 200 mg twice daily.

Participant milestones

Participant milestones
Measure	Placebo/Elagolix 150 mg QD Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg once daily (QD) for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg twice daily (BID) for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Treatment Period (6 Months) STARTED	102	111	142	140
Treatment Period (6 Months) Received Elagolix	102	111	142	140
Treatment Period (6 Months) COMPLETED	82	99	120	112
Treatment Period (6 Months) NOT COMPLETED	20	12	22	28
Post-treatment Follow-up (12 Months) STARTED	85	105	125	122
Post-treatment Follow-up (12 Months) COMPLETED	73	81	96	95
Post-treatment Follow-up (12 Months) NOT COMPLETED	12	24	29	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Elagolix 150 mg QD Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg once daily (QD) for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg twice daily (BID) for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Treatment Period (6 Months) Withdrawal by Subject	1	2	5	4
Treatment Period (6 Months) Adverse Event	7	8	8	9
Treatment Period (6 Months) Lost to Follow-up	3	0	4	3
Treatment Period (6 Months) Surgery or Invasive Intervention	2	0	0	2
Treatment Period (6 Months) Pregnancy	0	2	2	0
Treatment Period (6 Months) Non-compliance	1	0	0	3
Treatment Period (6 Months) Other	3	0	3	2
Treatment Period (6 Months) Bone Mineral Density (BMD) Decrease	0	0	0	4
Treatment Period (6 Months) Exclusionary Medication	2	0	0	0
Treatment Period (6 Months) Lack of Efficacy	1	0	0	1
Post-treatment Follow-up (12 Months) Withdrawal by Subject	4	7	6	10
Post-treatment Follow-up (12 Months) Adverse Event	0	0	1	0
Post-treatment Follow-up (12 Months) Lost to Follow-up	3	8	11	8
Post-treatment Follow-up (12 Months) Surgery or Invasive Intervention	2	4	4	1
Post-treatment Follow-up (12 Months) Exclusionary Medication	0	1	0	1
Post-treatment Follow-up (12 Months) Other	3	4	7	7

Baseline Characteristics

Global Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Women With Moderate to Severe Endometriosis-associated Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.	Total n=495 Participants Total of all reporting groups
Age, Continuous	33.5 years STANDARD_DEVIATION 7.00 • n=5 Participants	33.2 years STANDARD_DEVIATION 6.32 • n=7 Participants	33.2 years STANDARD_DEVIATION 7.02 • n=5 Participants	34.1 years STANDARD_DEVIATION 6.70 • n=4 Participants	33.5 years STANDARD_DEVIATION 6.76 • n=21 Participants
Sex: Female, Male Female	102 Participants n=5 Participants	111 Participants n=7 Participants	142 Participants n=5 Participants	140 Participants n=4 Participants	495 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants	21 Participants n=4 Participants	61 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	88 Participants n=5 Participants	100 Participants n=7 Participants	127 Participants n=5 Participants	119 Participants n=4 Participants	434 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized White	94 Participants n=5 Participants	100 Participants n=7 Participants	127 Participants n=5 Participants	126 Participants n=4 Participants	447 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants	12 Participants n=4 Participants	42 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Multi race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or other pacific islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

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

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline and month 6 data.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=81 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=98 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=122 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=116 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment	37.0 percentage of participants	57.1 percentage of participants	50.8 percentage of participants	75.9 percentage of participants

PRIMARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline and month 6 data.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=81 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=98 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=122 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=116 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment	27.2 percentage of participants	32.7 percentage of participants	66.4 percentage of participants	67.2 percentage of participants

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study and with available data at each time point

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 1	11.8 percentage of participants	24.5 percentage of participants	56.7 percentage of participants	74.3 percentage of participants
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 2	36.5 percentage of participants	62.3 percentage of participants	52.2 percentage of participants	79.1 percentage of participants
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 3	30.0 percentage of participants	64.1 percentage of participants	48.1 percentage of participants	77.1 percentage of participants
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 5	30.9 percentage of participants	59.0 percentage of participants	53.2 percentage of participants	82.9 percentage of participants
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 4	33.0 percentage of participants	64.7 percentage of participants	47.7 percentage of participants	80.0 percentage of participants

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study and with available data at each time point

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 1	12.7 percentage of participants	18.2 percentage of participants	61.7 percentage of participants	62.1 percentage of participants
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 3	18.9 percentage of participants	29.1 percentage of participants	66.2 percentage of participants	65.6 percentage of participants
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 4	27.3 percentage of participants	34.3 percentage of participants	64.8 percentage of participants	66.4 percentage of participants
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 5	28.4 percentage of participants	33.0 percentage of participants	67.5 percentage of participants	72.6 percentage of participants
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 2	20.8 percentage of participants	27.4 percentage of participants	61.8 percentage of participants	63.4 percentage of participants

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study and with available data at each time point; if a participant's mean score was not defined because all reports in that month were "Not Applicable," then that mean score was treated as missing.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 4	34.8 percentage of participants	32.3 percentage of participants	54.1 percentage of participants	60.2 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 6	28.8 percentage of participants	31.3 percentage of participants	45.9 percentage of participants	58.1 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 1	23.1 percentage of participants	27.3 percentage of participants	50.5 percentage of participants	63.4 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 2	30.6 percentage of participants	35.1 percentage of participants	47.0 percentage of participants	65.3 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 3	37.3 percentage of participants	33.3 percentage of participants	55.7 percentage of participants	61.2 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 5	30.0 percentage of participants	40.0 percentage of participants	52.3 percentage of participants	63.5 percentage of participants

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 1	-18.4 percent change Standard Deviation 41.71	-27.0 percent change Standard Deviation 55.50	-54.6 percent change Standard Deviation 41.79	-81.3 percent change Standard Deviation 36.00
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 4	-40.3 percent change Standard Deviation 51.25	-77.5 percent change Standard Deviation 41.25	-50.5 percent change Standard Deviation 39.97	-83.0 percent change Standard Deviation 36.23
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 5	-38.0 percent change Standard Deviation 50.01	-75.6 percent change Standard Deviation 47.88	-51.8 percent change Standard Deviation 39.25	-82.7 percent change Standard Deviation 33.89
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 6	-44.6 percent change Standard Deviation 45.08	-80.7 percent change Standard Deviation 38.43	-52.9 percent change Standard Deviation 39.52	-81.8 percent change Standard Deviation 33.57
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 2	-47.6 percent change Standard Deviation 50.17	-70.2 percent change Standard Deviation 55.81	-50.7 percent change Standard Deviation 41.16	-84.0 percent change Standard Deviation 33.76
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 3	-40.2 percent change Standard Deviation 51.63	-76.7 percent change Standard Deviation 48.73	-49.0 percent change Standard Deviation 41.98	-84.8 percent change Standard Deviation 32.01

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 1	-7.3 percent change Standard Deviation 57.59	-11.3 percent change Standard Deviation 64.29	-47.9 percent change Standard Deviation 39.03	-54.0 percent change Standard Deviation 41.77
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 2	-7.8 percent change Standard Deviation 71.50	-12.8 percent change Standard Deviation 143.81	-48.6 percent change Standard Deviation 38.70	-53.1 percent change Standard Deviation 42.04
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 4	-25.0 percent change Standard Deviation 53.14	-23.1 percent change Standard Deviation 123.65	-53.2 percent change Standard Deviation 37.47	-54.4 percent change Standard Deviation 40.89
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 5	-30.4 percent change Standard Deviation 44.88	-31.2 percent change Standard Deviation 113.03	-54.9 percent change Standard Deviation 39.53	-57.4 percent change Standard Deviation 42.84
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 6	-24.0 percent change Standard Deviation 62.40	-27.2 percent change Standard Deviation 164.50	-53.6 percent change Standard Deviation 40.41	-55.9 percent change Standard Deviation 41.01
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 3	-24.5 percent change Standard Deviation 53.77	-17.8 percent change Standard Deviation 130.92	-50.7 percent change Standard Deviation 38.41	-54.5 percent change Standard Deviation 41.70

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study and with available baseline data and data at each time point; participants with responses of 'Not Applicable' on all reported days during baseline or for the entire time point were excluded from the analysis.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=83 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=87 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=118 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=108 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 1	-10.4 percent change Standard Deviation 52.31	-16.9 percent change Standard Deviation 59.04	-43.7 percent change Standard Deviation 64.77	-48.7 percent change Standard Deviation 66.94
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 2	-12.0 percent change Standard Deviation 51.80	-19.2 percent change Standard Deviation 65.67	-38.0 percent change Standard Deviation 74.89	-51.1 percent change Standard Deviation 52.74
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 3	-22.1 percent change Standard Deviation 46.07	-26.4 percent change Standard Deviation 69.18	-43.4 percent change Standard Deviation 55.71	-49.1 percent change Standard Deviation 46.47
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 4	-22.3 percent change Standard Deviation 51.64	-12.6 percent change Standard Deviation 141.47	-49.1 percent change Standard Deviation 48.27	-48.5 percent change Standard Deviation 56.42
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 5	-25.7 percent change Standard Deviation 45.51	-9.5 percent change Standard Deviation 191.05	-57.0 percent change Standard Deviation 43.57	-42.7 percent change Standard Deviation 64.12
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 6	-18.8 percent change Standard Deviation 54.07	-28.3 percent change Standard Deviation 53.62	-51.3 percent change Standard Deviation 45.87	-49.7 percent change Standard Deviation 54.23

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Change From Baseline in Any Rescue Analgesic Use Month 1	-0.07 pills/day Standard Deviation 0.320	-0.16 pills/day Standard Deviation 0.389	-0.44 pills/day Standard Deviation 0.745	-0.47 pills/day Standard Deviation 0.711
Change From Baseline in Any Rescue Analgesic Use Month 2	-0.16 pills/day Standard Deviation 0.375	-0.24 pills/day Standard Deviation 0.510	-0.49 pills/day Standard Deviation 0.829	-0.52 pills/day Standard Deviation 0.774
Change From Baseline in Any Rescue Analgesic Use Month 3	-0.14 pills/day Standard Deviation 0.391	-0.24 pills/day Standard Deviation 0.524	-0.46 pills/day Standard Deviation 0.806	-0.53 pills/day Standard Deviation 0.774
Change From Baseline in Any Rescue Analgesic Use Month 4	-0.13 pills/day Standard Deviation 0.460	-0.28 pills/day Standard Deviation 0.483	-0.48 pills/day Standard Deviation 0.815	-0.54 pills/day Standard Deviation 0.811
Change From Baseline in Any Rescue Analgesic Use Month 5	-0.16 pills/day Standard Deviation 0.446	-0.29 pills/day Standard Deviation 0.539	-0.46 pills/day Standard Deviation 0.817	-0.57 pills/day Standard Deviation 0.758
Change From Baseline in Any Rescue Analgesic Use Month 6	-0.16 pills/day Standard Deviation 0.410	-0.28 pills/day Standard Deviation 0.513	-0.45 pills/day Standard Deviation 0.834	-0.59 pills/day Standard Deviation 0.799

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Change From Baseline in NSAID Rescue Analgesic Use Month 1	-0.05 pills/day Standard Deviation 0.209	-0.12 pills/day Standard Deviation 0.263	-0.25 pills/day Standard Deviation 0.590	-0.28 pills/day Standard Deviation 0.363
Change From Baseline in NSAID Rescue Analgesic Use Month 2	-0.10 pills/day Standard Deviation 0.271	-0.18 pills/day Standard Deviation 0.343	-0.29 pills/day Standard Deviation 0.624	-0.29 pills/day Standard Deviation 0.389
Change From Baseline in NSAID Rescue Analgesic Use Month 3	-0.11 pills/day Standard Deviation 0.281	-0.18 pills/day Standard Deviation 0.336	-0.27 pills/day Standard Deviation 0.550	-0.30 pills/day Standard Deviation 0.370
Change From Baseline in NSAID Rescue Analgesic Use Month 4	-0.09 pills/day Standard Deviation 0.297	-0.20 pills/day Standard Deviation 0.334	-0.28 pills/day Standard Deviation 0.531	-0.30 pills/day Standard Deviation 0.379
Change From Baseline in NSAID Rescue Analgesic Use Month 5	-0.11 pills/day Standard Deviation 0.316	-0.21 pills/day Standard Deviation 0.353	-0.27 pills/day Standard Deviation 0.556	-0.31 pills/day Standard Deviation 0.376
Change From Baseline in NSAID Rescue Analgesic Use Month 6	-0.10 pills/day Standard Deviation 0.241	-0.20 pills/day Standard Deviation 0.369	-0.26 pills/day Standard Deviation 0.569	-0.32 pills/day Standard Deviation 0.380

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Change From Baseline in Opioid Rescue Analgesic Use Month 1	-0.02 pills/day Standard Deviation 0.197	-0.04 pills/day Standard Deviation 0.243	-0.19 pills/day Standard Deviation 0.526	-0.20 pills/day Standard Deviation 0.596
Change From Baseline in Opioid Rescue Analgesic Use Month 2	-0.06 pills/day Standard Deviation 0.214	-0.06 pills/day Standard Deviation 0.270	-0.19 pills/day Standard Deviation 0.573	-0.23 pills/day Standard Deviation 0.655
Change From Baseline in Opioid Rescue Analgesic Use Month 3	-0.04 pills/day Standard Deviation 0.217	-0.06 pills/day Standard Deviation 0.309	-0.19 pills/day Standard Deviation 0.613	-0.23 pills/day Standard Deviation 0.662
Change From Baseline in Opioid Rescue Analgesic Use Month 4	-0.05 pills/day Standard Deviation 0.262	-0.08 pills/day Standard Deviation 0.231	-0.20 pills/day Standard Deviation 0.620	-0.24 pills/day Standard Deviation 0.693
Change From Baseline in Opioid Rescue Analgesic Use Month 5	-0.05 pills/day Standard Deviation 0.227	-0.08 pills/day Standard Deviation 0.273	-0.19 pills/day Standard Deviation 0.613	-0.26 pills/day Standard Deviation 0.643
Change From Baseline in Opioid Rescue Analgesic Use Month 6	-0.06 pills/day Standard Deviation 0.237	-0.07 pills/day Standard Deviation 0.271	-0.20 pills/day Standard Deviation 0.623	-0.27 pills/day Standard Deviation 0.680

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 1	-12.0 percent change Standard Deviation 44.71	-18.2 percent change Standard Deviation 51.75	-50.8 percent change Standard Deviation 36.58	-58.7 percent change Standard Deviation 37.07
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 2	-20.7 percent change Standard Deviation 40.87	-25.8 percent change Standard Deviation 87.35	-50.7 percent change Standard Deviation 36.08	-58.7 percent change Standard Deviation 36.31
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 3	-27.7 percent change Standard Deviation 39.61	-35.0 percent change Standard Deviation 65.06	-52.7 percent change Standard Deviation 36.40	-59.5 percent change Standard Deviation 35.99
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 4	-31.2 percent change Standard Deviation 43.28	-38.8 percent change Standard Deviation 58.04	-54.7 percent change Standard Deviation 33.26	-60.4 percent change Standard Deviation 34.77
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 5	-29.2 percent change Standard Deviation 52.99	-45.6 percent change Standard Deviation 60.86	-56.1 percent change Standard Deviation 35.81	-62.3 percent change Standard Deviation 34.99
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 6	-30.7 percent change Standard Deviation 42.08	-41.7 percent change Standard Deviation 83.80	-53.9 percent change Standard Deviation 35.06	-61.1 percent change Standard Deviation 33.71

SECONDARY outcome

Timeframe: Months 1, 2, 3, 4, 5, and 6

Population: Participants who received at least 1 dose of double-blind study drug in this extension study and with available data at each time point.

The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories: 1. Very Much Improved 2. Much Improved 3. Minimally Improved 4. Not Changed 5. Minimally Worse 6. Much Worse 7. Very Much Worse

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 6	65.8 percentage of participants	76.3 percentage of participants	75.4 percentage of participants	84.0 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 1	50.0 percentage of participants	56.8 percentage of participants	65.7 percentage of participants	78.3 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 2	58.7 percentage of participants	74.5 percentage of participants	69.1 percentage of participants	78.9 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 3	63.6 percentage of participants	70.9 percentage of participants	67.9 percentage of participants	77.2 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 4	61.4 percentage of participants	75.2 percentage of participants	71.1 percentage of participants	82.1 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 5	67.1 percentage of participants	81.0 percentage of participants	71.8 percentage of participants	82.1 percentage of participants

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension Month 6	-10.60 units on a scale Standard Deviation 20.827	-15.61 units on a scale Standard Deviation 21.047	-32.95 units on a scale Standard Deviation 23.674	-38.48 units on a scale Standard Deviation 21.924
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension Month 1	-8.02 units on a scale Standard Deviation 17.828	-12.18 units on a scale Standard Deviation 17.465	-32.25 units on a scale Standard Deviation 21.235	-36.45 units on a scale Standard Deviation 22.320
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension Month 3	-11.12 units on a scale Standard Deviation 22.424	-15.25 units on a scale Standard Deviation 21.467	-32.00 units on a scale Standard Deviation 23.172	-37.42 units on a scale Standard Deviation 21.492

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=90 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=97 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=109 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=111 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension Month 1	-3.29 units on a scale Standard Deviation 13.655	-10.35 units on a scale Standard Deviation 16.846	-24.17 units on a scale Standard Deviation 26.010	-28.37 units on a scale Standard Deviation 29.886
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension Month 3	-9.26 units on a scale Standard Deviation 20.264	-12.50 units on a scale Standard Deviation 22.449	-24.61 units on a scale Standard Deviation 26.986	-28.66 units on a scale Standard Deviation 31.580
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension Month 6	-9.36 units on a scale Standard Deviation 19.294	-7.30 units on a scale Standard Deviation 22.963	-23.21 units on a scale Standard Deviation 26.310	-33.21 units on a scale Standard Deviation 31.988

SECONDARY outcome

Population: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline data and data at each time point. Hours lost from workplace were only calculated for participants who were employed.

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=91 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=126 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=130 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Absenteeism from workplace	-2.82 hours Standard Deviation 5.648	-1.33 hours Standard Deviation 8.945	-1.25 hours Standard Deviation 4.377	-1.73 hours Standard Deviation 4.133
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Presenteeism from workplace	-10.31 hours Standard Deviation 15.902	-8.37 hours Standard Deviation 9.675	-8.38 hours Standard Deviation 12.489	-10.63 hours Standard Deviation 9.837
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Total hours of work lost from workplace	-13.22 hours Standard Deviation 16.663	-9.70 hours Standard Deviation 13.683	-9.36 hours Standard Deviation 13.365	-12.02 hours Standard Deviation 10.447
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Absenteeism from household	-3.17 hours Standard Deviation 6.241	-2.68 hours Standard Deviation 3.779	-3.56 hours Standard Deviation 4.924	-3.50 hours Standard Deviation 4.180
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Presenteeism from household	-2.47 hours Standard Deviation 6.581	-2.19 hours Standard Deviation 4.973	-2.33 hours Standard Deviation 5.182	-2.74 hours Standard Deviation 5.308
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Total hours of work lost from household	-5.64 hours Standard Deviation 9.919	-4.86 hours Standard Deviation 7.185	-5.84 hours Standard Deviation 7.844	-6.17 hours Standard Deviation 7.930

SECONDARY outcome

Timeframe: 6 months

Population: Participants who received at least 1 dose of double-blind study drug in this extension study

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

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Number of Participants With Non-study Health Visits During the Treatment Period	48 Participants	65 Participants	76 Participants	76 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Participants who received at least 1 dose of double-blind study drug in this extension study and who underwent hospitalization

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.

Outcome measures

Outcome measures
Measure	Placebo/Elagolix 150 mg QD n=9 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=11 Participants Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=10 Participants Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=13 Participants Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Number of Days in Hospital During the Treatment Period	2.0 days Interval 1.0 to 6.0	4.0 days Interval 2.0 to 13.0	3.0 days Interval 1.0 to 7.0	3.0 days Interval 1.0 to 7.0

Adverse Events

Placebo/Elagolix 150 mg QD

Serious events: 4 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo/Elagolix 200 mg BID

Serious events: 8 serious events

Other events: 74 other events

Deaths: 0 deaths

Elagolix/Elagolix 150 mg QD

Serious events: 7 serious events

Other events: 65 other events

Deaths: 0 deaths

Elagolix/Elagolix 200 mg BID

Serious events: 8 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo/Elagolix 150 mg QD n=102 participants at risk Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 participants at risk Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 participants at risk Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 participants at risk Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Gastrointestinal disorders ABDOMINAL HERNIA	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders ABDOMINAL PAIN	2.0% 2/102 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.70% 1/142 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders ABDOMINAL PAIN LOWER	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders GASTROINTESTINAL MOTILITY DISORDER	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.70% 1/142 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders IRRITABLE BOWEL SYNDROME	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
General disorders PYREXIA	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.70% 1/142 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations DENGUE FEVER	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations DIVERTICULITIS	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations POSTOPERATIVE WOUND INFECTION	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Injury, poisoning and procedural complications CARBON MONOXIDE POISONING	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Injury, poisoning and procedural complications INCISIONAL HERNIA	0.98% 1/102 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Injury, poisoning and procedural complications LIGAMENT RUPTURE	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Injury, poisoning and procedural complications PROCEDURAL HYPERTENSION	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Injury, poisoning and procedural complications TIBIA FRACTURE	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.98% 1/102 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Musculoskeletal and connective tissue disorders OSTEOCHONDROSIS	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PELVIC NEOPLASM	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TERATOMA	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.70% 1/142 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Pregnancy, puerperium and perinatal conditions ABORTION SPONTANEOUS	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders ANXIETY	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Reproductive system and breast disorders OVARIAN CYST	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Reproductive system and breast disorders PELVIC PAIN	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.70% 1/142 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Reproductive system and breast disorders PERINEAL PAIN	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.70% 1/142 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.90% 1/111 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.71% 1/140 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Respiratory, thoracic and mediastinal disorders NASAL POLYPS	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.70% 1/142 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Surgical and medical procedures ABORTION INDUCED	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/111 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	1.4% 2/142 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/140 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).

Measure	Placebo/Elagolix 150 mg QD n=102 participants at risk Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-821.	Placebo/Elagolix 200 mg BID n=111 participants at risk Participants who received placebo in pivotal Study M12-671 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-821.	Elagolix/Elagolix 150 mg QD n=142 participants at risk Participants were randomized to elagolix 150 mg QD in pivotal Study M12-671 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-821.	Elagolix/Elagolix 200 mg BID n=140 participants at risk Participants were randomized to elagolix 200 mg BID in pivotal Study M12-671 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-821.
Gastrointestinal disorders NAUSEA	5.9% 6/102 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	11.7% 13/111 • Number of events 14 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	9.9% 14/142 • Number of events 15 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	3.6% 5/140 • Number of events 5 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
General disorders FATIGUE	0.00% 0/102 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	5.4% 6/111 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	1.4% 2/140 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations NASOPHARYNGITIS	5.9% 6/102 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	9.0% 10/111 • Number of events 10 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	4.2% 6/142 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	6.4% 9/140 • Number of events 10 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations SINUSITIS	5.9% 6/102 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	5.4% 6/111 • Number of events 8 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	5.6% 8/142 • Number of events 9 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	5.7% 8/140 • Number of events 8 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	4.9% 5/102 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	5.4% 6/111 • Number of events 7 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	4.2% 6/142 • Number of events 8 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	4.3% 6/140 • Number of events 7 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations URINARY TRACT INFECTION	2.9% 3/102 • Number of events 3 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	8.1% 9/111 • Number of events 12 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	7.0% 10/142 • Number of events 11 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	7.9% 11/140 • Number of events 13 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Investigations BONE DENSITY DECREASED	0.98% 1/102 • Number of events 1 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	1.8% 2/111 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/142 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	5.7% 8/140 • Number of events 8 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Musculoskeletal and connective tissue disorders ARTHRALGIA	8.8% 9/102 • Number of events 10 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	10.8% 12/111 • Number of events 13 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	4.2% 6/142 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	6.4% 9/140 • Number of events 10 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Musculoskeletal and connective tissue disorders BACK PAIN	2.0% 2/102 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	5.4% 6/111 • Number of events 7 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	4.2% 6/142 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	7.1% 10/140 • Number of events 11 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Nervous system disorders HEADACHE	12.7% 13/102 • Number of events 15 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	16.2% 18/111 • Number of events 20 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	6.3% 9/142 • Number of events 11 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	6.4% 9/140 • Number of events 9 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders ANXIETY	2.9% 3/102 • Number of events 3 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	6.3% 7/111 • Number of events 7 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 4/142 • Number of events 5 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	1.4% 2/140 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders INSOMNIA	3.9% 4/102 • Number of events 4 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	7.2% 8/111 • Number of events 8 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 4/142 • Number of events 4 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	2.1% 3/140 • Number of events 3 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders MOOD SWINGS	6.9% 7/102 • Number of events 7 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	6.3% 7/111 • Number of events 7 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	2.1% 3/142 • Number of events 3 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	1.4% 2/140 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Reproductive system and breast disorders AMENORRHOEA	3.9% 4/102 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	12.6% 14/111 • Number of events 16 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 4/142 • Number of events 4 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	1.4% 2/140 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Skin and subcutaneous tissue disorders ACNE	5.9% 6/102 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	5.4% 6/111 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	3.5% 5/142 • Number of events 6 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	1.4% 2/140 • Number of events 2 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).
Vascular disorders HOT FLUSH	14.7% 15/102 • Number of events 16 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	40.5% 45/111 • Number of events 47 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	4.9% 7/142 • Number of events 7 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).	7.9% 11/140 • Number of events 11 • From the date of the first dose of study drug in Study M12-821 through up to 30 days after the last dose of study drug (up to 7 months).