Trial Outcomes & Findings for Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Adults With Moderate to Severe Endometriosis-Associated Pain (NCT NCT01760954)

NCT ID: NCT01760954

Last Updated: 2021-07-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 506 participants
• Primary outcome 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
• Results posted on: 2021-07-13

Participant Flow

Participants who completed the 6-month Treatment Period in the pivotal Study M12-665 (NCT01620528) were eligible to enter this extension study. A total of 506 participants were enrolled at 131 sites in the United States, Puerto Rico, and Canada. Two enrolled participants did not receive study drug and are not included in the tables reported below.

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

Measure	Elagolix/Elagolix 150 mg QD Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Treatment Period (6 Months) STARTED	149	138	108	109
Treatment Period (6 Months) COMPLETED	116	110	87	83
Treatment Period (6 Months) NOT COMPLETED	33	28	21	26
Post-treatment Follow-up (12 Months) STARTED	126	118	86	87
Post-treatment Follow-up (12 Months) COMPLETED	96	83	65	67
Post-treatment Follow-up (12 Months) NOT COMPLETED	30	35	21	20

Reasons for withdrawal

Measure	Elagolix/Elagolix 150 mg QD Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Treatment Period (6 Months) Withdrawal by Subject	8	8	4	5
Treatment Period (6 Months) Adverse Event	5	3	4	10
Treatment Period (6 Months) Lost to Follow-up	9	1	4	3
Treatment Period (6 Months) Surgery or invasive intervention for end	3	3	3	2
Treatment Period (6 Months) Pregnancy	5	0	3	2
Treatment Period (6 Months) Non-compliance	1	4	0	3
Treatment Period (6 Months) Other	0	3	3	1
Treatment Period (6 Months) Decrease in Bone Mineral Density (BMD)	1	6	0	0
Treatment Period (6 Months) Exclusionary Medication	1	0	0	0
Post-treatment Follow-up (12 Months) Withdrawal by Subject	6	6	4	9
Post-treatment Follow-up (12 Months) Lost to Follow-up	4	7	2	0
Post-treatment Follow-up (12 Months) Surgery or invasive intervention	6	10	5	5
Post-treatment Follow-up (12 Months) Received Exclusionary Medication	1	4	0	0
Post-treatment Follow-up (12 Months) Return of Menses and Acceptable BMD	0	0	1	0
Post-treatment Follow-up (12 Months) Other	13	8	9	6

Baseline Characteristics

Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Adults With Moderate to Severe Endometriosis-Associated Pain

Baseline characteristics by cohort

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.	Total n=504 Participants Total of all reporting groups
Age, Continuous	31.8 years STANDARD_DEVIATION 6.52 • n=5 Participants	31.3 years STANDARD_DEVIATION 6.32 • n=7 Participants	32.4 years STANDARD_DEVIATION 6.08 • n=5 Participants	32.2 years STANDARD_DEVIATION 6.38 • n=4 Participants	31.9 years STANDARD_DEVIATION 6.34 • n=21 Participants
Sex: Female, Male Female	149 Participants n=5 Participants	138 Participants n=7 Participants	108 Participants n=5 Participants	109 Participants n=4 Participants	504 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	23 Participants n=5 Participants	21 Participants n=7 Participants	19 Participants n=5 Participants	22 Participants n=4 Participants	85 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	126 Participants n=5 Participants	117 Participants n=7 Participants	89 Participants n=5 Participants	87 Participants n=4 Participants	419 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	133 Participants n=5 Participants	126 Participants n=7 Participants	96 Participants n=5 Participants	95 Participants n=4 Participants	450 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants	41 Participants n=21 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Multi race	1 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

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

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 -0.81 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.

Outcome measures

Measure	Elagolix/Elagolix 150 mg QD n=117 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=110 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=86 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=87 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment	52.1 percentage of participants	78.2 percentage of participants	32.6 percentage of participants	64.4 percentage of participants

PRIMARY outcome

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

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 -0.36 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.

Outcome measures

Measure	Elagolix/Elagolix 150 mg QD n=117 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=110 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=86 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=87 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment	67.5 percentage of participants	69.1 percentage of participants	39.5 percentage of participants	57.5 percentage of participants

SECONDARY outcome

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

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

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.

Outcome measures

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 1	48.0 percentage of participants	80.9 percentage of participants	21.0 percentage of participants	20.6 percentage of participants
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 2	51.1 percentage of participants	78.9 percentage of participants	40.2 percentage of participants	60.0 percentage of participants
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 3	49.2 percentage of participants	80.5 percentage of participants	36.8 percentage of participants	54.3 percentage of participants
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 4	53.9 percentage of participants	79.8 percentage of participants	39.6 percentage of participants	58.2 percentage of participants
Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment Month 5	54.0 percentage of participants	83.3 percentage of participants	32.6 percentage of participants	64.0 percentage of participants

SECONDARY outcome

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

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

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.

Outcome measures

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 1	55.4 percentage of participants	74.3 percentage of participants	23.8 percentage of participants	29.0 percentage of participants
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 2	62.6 percentage of participants	69.5 percentage of participants	38.1 percentage of participants	41.0 percentage of participants
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 3	61.4 percentage of participants	70.7 percentage of participants	33.7 percentage of participants	45.7 percentage of participants
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 4	64.1 percentage of participants	75.6 percentage of participants	39.6 percentage of participants	47.3 percentage of participants
Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment Month 5	61.3 percentage of participants	71.9 percentage of participants	40.4 percentage of participants	51.7 percentage of participants

SECONDARY outcome

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

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 -0.36 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.

Outcome measures

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 1	50.0 percentage of participants	61.3 percentage of participants	33.3 percentage of participants	15.6 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 2	51.9 percentage of participants	58.3 percentage of participants	35.8 percentage of participants	30.0 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 3	50.0 percentage of participants	63.8 percentage of participants	36.4 percentage of participants	32.8 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 4	48.9 percentage of participants	65.3 percentage of participants	46.9 percentage of participants	41.9 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 5	46.6 percentage of participants	65.3 percentage of participants	38.1 percentage of participants	39.7 percentage of participants
Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment Month 6	45.2 percentage of participants	60.0 percentage of participants	39.0 percentage of participants	43.1 percentage of participants

SECONDARY outcome

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

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

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 1	-46.7 percent change Standard Deviation 44.00	-82.7 percent change Standard Deviation 34.81	-19.0 percent change Standard Deviation 50.35	-19.3 percent change Standard Deviation 51.09
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 2	-46.7 percent change Standard Deviation 44.93	-84.8 percent change Standard Deviation 29.81	-46.6 percent change Standard Deviation 47.39	-67.3 percent change Standard Deviation 47.74
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 3	-47.9 percent change Standard Deviation 42.37	-84.5 percent change Standard Deviation 33.24	-36.3 percent change Standard Deviation 57.28	-65.9 percent change Standard Deviation 47.17
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 4	-51.4 percent change Standard Deviation 44.65	-85.1 percent change Standard Deviation 30.52	-38.2 percent change Standard Deviation 52.48	-67.4 percent change Standard Deviation 47.80
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 5	-52.4 percent change Standard Deviation 43.55	-83.4 percent change Standard Deviation 31.19	-33.4 percent change Standard Deviation 48.29	-77.2 percent change Standard Deviation 41.90
Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment Month 6	-49.2 percent change Standard Deviation 43.75	-82.0 percent change Standard Deviation 33.29	-37.9 percent change Standard Deviation 47.43	-71.6 percent change Standard Deviation 47.81

SECONDARY outcome

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

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

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 1	-37.4 percent change Standard Deviation 43.90	-54.5 percent change Standard Deviation 40.35	-9.6 percent change Standard Deviation 104.61	-20.7 percent change Standard Deviation 51.24
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 2	-41.4 percent change Standard Deviation 41.49	-56.4 percent change Standard Deviation 38.54	-22.6 percent change Standard Deviation 85.60	-18.0 percent change Standard Deviation 98.73
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 3	-44.0 percent change Standard Deviation 40.44	-56.8 percent change Standard Deviation 39.14	-19.7 percent change Standard Deviation 93.18	-30.2 percent change Standard Deviation 57.07
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 4	-47.2 percent change Standard Deviation 41.30	-59.6 percent change Standard Deviation 37.30	-32.0 percent change Standard Deviation 66.23	-33.9 percent change Standard Deviation 53.27
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 5	-45.3 percent change Standard Deviation 41.05	-58.0 percent change Standard Deviation 39.18	-17.7 percent change Standard Deviation 126.45	-42.5 percent change Standard Deviation 43.01
Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment Month 6	-48.9 percent change Standard Deviation 41.69	-56.5 percent change Standard Deviation 40.15	-10.2 percent change Standard Deviation 163.42	-43.9 percent change Standard Deviation 43.57

SECONDARY outcome

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

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

Measure	Elagolix/Elagolix 150 mg QD n=123 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=109 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=85 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=82 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 1	-32.8 percent change Standard Deviation 63.13	-39.5 percent change Standard Deviation 71.30	-12.9 percent change Standard Deviation 62.92	-1.1 percent change Standard Deviation 63.74
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 2	-36.2 percent change Standard Deviation 56.97	-40.4 percent change Standard Deviation 63.27	-16.2 percent change Standard Deviation 82.49	-27.1 percent change Standard Deviation 48.17
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 3	-36.1 percent change Standard Deviation 55.41	-38.6 percent change Standard Deviation 75.34	-14.1 percent change Standard Deviation 76.54	-23.5 percent change Standard Deviation 50.71
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 4	-35.0 percent change Standard Deviation 55.27	-48.6 percent change Standard Deviation 63.81	-24.3 percent change Standard Deviation 76.26	-20.7 percent change Standard Deviation 71.89
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 5	-34.9 percent change Standard Deviation 58.90	-44.8 percent change Standard Deviation 76.01	-20.2 percent change Standard Deviation 62.92	-27.5 percent change Standard Deviation 58.78
Percent Change From Baseline in Dyspareunia Based on Daily Assessment Month 6	-30.7 percent change Standard Deviation 66.57	-41.7 percent change Standard Deviation 68.50	-28.0 percent change Standard Deviation 66.59	-12.6 percent change Standard Deviation 107.83

SECONDARY outcome

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

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, 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.

Outcome measures

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Change From Baseline in Any Rescue Analgesic Use Month 1	-0.35 pills/day Standard Deviation 0.743	-0.58 pills/day Standard Deviation 0.687	-0.15 pills/day Standard Deviation 0.398	-0.16 pills/day Standard Deviation 0.486
Change From Baseline in Any Rescue Analgesic Use Month 2	-0.35 pills/day Standard Deviation 0.646	-0.59 pills/day Standard Deviation 0.735	-0.24 pills/day Standard Deviation 0.471	-0.28 pills/day Standard Deviation 0.481
Change From Baseline in Any Rescue Analgesic Use Month 3	-0.37 pills/day Standard Deviation 0.733	-0.61 pills/day Standard Deviation 0.785	-0.25 pills/day Standard Deviation 0.525	-0.32 pills/day Standard Deviation 0.470
Change From Baseline in Any Rescue Analgesic Use Month 4	-0.40 pills/day Standard Deviation 0.703	-0.62 pills/day Standard Deviation 0.697	-0.26 pills/day Standard Deviation 0.521	-0.35 pills/day Standard Deviation 0.616
Change From Baseline in Any Rescue Analgesic Use Month 5	-0.41 pills/day Standard Deviation 0.687	-0.59 pills/day Standard Deviation 0.685	-0.27 pills/day Standard Deviation 0.626	-0.34 pills/day Standard Deviation 0.590
Change From Baseline in Any Rescue Analgesic Use Month 6	-0.40 pills/day Standard Deviation 0.699	-0.56 pills/day Standard Deviation 0.667	-0.22 pills/day Standard Deviation 0.616	-0.38 pills/day Standard Deviation 0.602

SECONDARY outcome

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

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, 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.

Outcome measures

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Change From Baseline in NSAID Rescue Analgesic Use Month 1	-0.24 pills/day Standard Deviation 0.484	-0.34 pills/day Standard Deviation 0.469	-0.07 pills/day Standard Deviation 0.217	-0.09 pills/day Standard Deviation 0.314
Change From Baseline in NSAID Rescue Analgesic Use Month 2	-0.24 pills/day Standard Deviation 0.472	-0.34 pills/day Standard Deviation 0.462	-0.12 pills/day Standard Deviation 0.302	-0.14 pills/day Standard Deviation 0.311
Change From Baseline in NSAID Rescue Analgesic Use Month 3	-0.24 pills/day Standard Deviation 0.488	-0.34 pills/day Standard Deviation 0.460	-0.12 pills/day Standard Deviation 0.324	-0.14 pills/day Standard Deviation 0.346
Change From Baseline in NSAID Rescue Analgesic Use Month 4	-0.25 pills/day Standard Deviation 0.461	-0.35 pills/day Standard Deviation 0.450	-0.13 pills/day Standard Deviation 0.336	-0.17 pills/day Standard Deviation 0.397
Change From Baseline in NSAID Rescue Analgesic Use Month 5	-0.27 pills/day Standard Deviation 0.494	-0.32 pills/day Standard Deviation 0.417	-0.13 pills/day Standard Deviation 0.378	-0.17 pills/day Standard Deviation 0.394
Change From Baseline in NSAID Rescue Analgesic Use Month 6	-0.27 pills/day Standard Deviation 0.517	-0.31 pills/day Standard Deviation 0.430	-0.12 pills/day Standard Deviation 0.380	-0.23 pills/day Standard Deviation 0.453

SECONDARY outcome

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

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, 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.

Outcome measures

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Change From Baseline in Opioid Rescue Analgesic Use Month 1	-0.11 pills/day Standard Deviation 0.547	-0.24 pills/day Standard Deviation 0.469	-0.09 pills/day Standard Deviation 0.272	-0.07 pills/day Standard Deviation 0.329
Change From Baseline in Opioid Rescue Analgesic Use Month 2	-0.11 pills/day Standard Deviation 0.441	-0.25 pills/day Standard Deviation 0.532	-0.12 pills/day Standard Deviation 0.267	-0.14 pills/day Standard Deviation 0.344
Change From Baseline in Opioid Rescue Analgesic Use Month 3	-0.13 pills/day Standard Deviation 0.540	-0.28 pills/day Standard Deviation 0.599	-0.13 pills/day Standard Deviation 0.298	-0.17 pills/day Standard Deviation 0.338
Change From Baseline in Opioid Rescue Analgesic Use Month 4	-0.15 pills/day Standard Deviation 0.541	-0.27 pills/day Standard Deviation 0.581	-0.13 pills/day Standard Deviation 0.298	-0.19 pills/day Standard Deviation 0.501
Change From Baseline in Opioid Rescue Analgesic Use Month 5	-0.15 pills/day Standard Deviation 0.469	-0.27 pills/day Standard Deviation 0.558	-0.14 pills/day Standard Deviation 0.384	-0.17 pills/day Standard Deviation 0.444
Change From Baseline in Opioid Rescue Analgesic Use Month 6	-0.13 pills/day Standard Deviation 0.439	-0.25 pills/day Standard Deviation 0.534	-0.10 pills/day Standard Deviation 0.369	-0.16 pills/day Standard Deviation 0.392

SECONDARY outcome

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

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.

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

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=107 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 1	-41.0 percent change Standard Deviation 39.85	-60.0 percent change Standard Deviation 36.93	-9.2 percent change Standard Deviation 81.63	-22.3 percent change Standard Deviation 34.41
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 2	-44.4 percent change Standard Deviation 38.35	-62.1 percent change Standard Deviation 33.80	-31.2 percent change Standard Deviation 39.22	-34.6 percent change Standard Deviation 41.07
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 3	-45.5 percent change Standard Deviation 36.23	-62.2 percent change Standard Deviation 34.10	-28.0 percent change Standard Deviation 55.94	-39.9 percent change Standard Deviation 41.48
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 4	-47.7 percent change Standard Deviation 37.99	-63.5 percent change Standard Deviation 32.93	-32.8 percent change Standard Deviation 57.74	-40.0 percent change Standard Deviation 54.65
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 5	-46.4 percent change Standard Deviation 38.07	-62.1 percent change Standard Deviation 34.56	-29.0 percent change Standard Deviation 71.65	-46.4 percent change Standard Deviation 39.07
Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) Month 6	-48.2 percent change Standard Deviation 38.97	-60.7 percent change Standard Deviation 36.09	-27.8 percent change Standard Deviation 64.75	-45.5 percent change Standard Deviation 44.10

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

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=148 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 2	64.7 percentage of participants	87.3 percentage of participants	65.7 percentage of participants	70.0 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 1	63.3 percentage of participants	86.4 percentage of participants	47.1 percentage of participants	45.5 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 3	64.3 percentage of participants	87.4 percentage of participants	73.7 percentage of participants	71.3 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 4	70.7 percentage of participants	91.5 percentage of participants	73.9 percentage of participants	70.8 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 5	75.2 percentage of participants	87.5 percentage of participants	66.3 percentage of participants	78.7 percentage of participants
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved Month 6	69.4 percentage of participants	91.2 percentage of participants	70.4 percentage of participants	79.3 percentage of participants

SECONDARY outcome

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

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

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=135 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension Month 1	-29.50 units on a scale Standard Deviation 20.917	-40.28 units on a scale Standard Deviation 21.503	-12.98 units on a scale Standard Deviation 17.426	-13.27 units on a scale Standard Deviation 17.010
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension Month 3	-30.10 units on a scale Standard Deviation 20.231	-43.16 units on a scale Standard Deviation 20.951	-17.87 units on a scale Standard Deviation 21.160	-21.87 units on a scale Standard Deviation 24.087
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension Month 6	-31.18 units on a scale Standard Deviation 22.213	-41.62 units on a scale Standard Deviation 21.553	-15.63 units on a scale Standard Deviation 22.676	-25.17 units on a scale Standard Deviation 23.387

SECONDARY outcome

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

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

Measure	Elagolix/Elagolix 150 mg QD n=120 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=102 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=97 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=95 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension Month 1	-19.81 units on a scale Standard Deviation 23.828	-29.42 units on a scale Standard Deviation 28.257	-8.15 units on a scale Standard Deviation 21.287	-9.86 units on a scale Standard Deviation 17.484
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension Month 3	-20.88 units on a scale Standard Deviation 24.979	-27.27 units on a scale Standard Deviation 30.431	-15.00 units on a scale Standard Deviation 22.890	-18.24 units on a scale Standard Deviation 23.015
Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension Month 6	-24.23 units on a scale Standard Deviation 27.065	-30.55 units on a scale Standard Deviation 33.831	-12.45 units on a scale Standard Deviation 26.858	-23.17 units on a scale Standard Deviation 25.763

SECONDARY outcome

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

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

Measure	Elagolix/Elagolix 150 mg QD n=140 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=135 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=102 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=106 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Absenteeism from workplace	-1.84 hours Standard Deviation 5.636	-3.01 hours Standard Deviation 6.771	-2.15 hours Standard Deviation 4.258	-2.78 hours Standard Deviation 4.730
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Presenteeism from workplace	-11.14 hours Standard Deviation 8.484	-12.45 hours Standard Deviation 10.464	-8.29 hours Standard Deviation 8.307	-10.15 hours Standard Deviation 10.724
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Total hours of work lost from workplace	-12.98 hours Standard Deviation 9.662	-15.15 hours Standard Deviation 11.653	-10.44 hours Standard Deviation 9.422	-13.03 hours Standard Deviation 11.911
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Absenteeism from household	-3.10 hours Standard Deviation 7.588	-3.69 hours Standard Deviation 4.486	-3.76 hours Standard Deviation 7.457	-2.80 hours Standard Deviation 4.971
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Presenteeism from household	-2.72 hours Standard Deviation 6.459	-2.49 hours Standard Deviation 4.531	-2.95 hours Standard Deviation 4.793	-2.72 hours Standard Deviation 4.698
Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household Total hours of work lost from household	-5.82 hours Standard Deviation 11.356	-6.15 hours Standard Deviation 7.628	-6.90 hours Standard Deviation 11.673	-5.52 hours Standard Deviation 6.934

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

Measure	Elagolix/Elagolix 150 mg QD n=149 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Number of Participants With Non-study Health Visits During the Treatment Period	81 Participants	68 Participants	59 Participants	48 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

Measure	Elagolix/Elagolix 150 mg QD n=7 Participants Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=6 Participants Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=5 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=4 Participants Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Number of Days in Hospital During the Treatment Period	2.0 days Interval 1.0 to 6.0	1.5 days Interval 1.0 to 4.0	3.0 days Interval 2.0 to 8.0	1.0 days Interval 1.0 to 2.0

Adverse Events

Elagolix/Elagolix 150 mg QD

Serious events: 5 serious events

Other events: 79 other events

Deaths: 0 deaths

Elagolix/Elagolix 200 mg BID

Serious events: 4 serious events

Other events: 74 other events

Deaths: 0 deaths

Placebo/Elagolix 150 mg QD

Serious events: 5 serious events

Other events: 55 other events

Deaths: 0 deaths

Placebo/Elagolix 200 mg BID

Serious events: 5 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Measure	Elagolix/Elagolix 150 mg QD n=149 participants at risk Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 participants at risk Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 participants at risk Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 participants at risk Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Cardiac disorders SUPRAVENTRICULAR TACHYCARDIA	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.93% 1/108 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders ABDOMINAL PAIN UPPER	0.67% 1/149 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders COLITIS	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.93% 1/108 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.67% 1/149 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders INCARCERATED UMBILICAL HERNIA	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.93% 1/108 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders NAUSEA	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.92% 1/109 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders VOMITING	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.92% 1/109 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.92% 1/109 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations DIVERTICULITIS	0.67% 1/149 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Injury, poisoning and procedural complications JOINT INJURY	0.67% 1/149 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	0.67% 1/149 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Musculoskeletal and connective tissue disorders NECK PAIN	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.72% 1/138 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 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) LUNG ADENOCARCINOMA	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.93% 1/108 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Nervous system disorders MIGRAINE	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.72% 1/138 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 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% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.92% 1/109 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders AFFECTIVE DISORDER	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.72% 1/138 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders SUICIDAL IDEATION	0.67% 1/149 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 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% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.93% 1/108 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 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% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	1.4% 2/138 • Number of events 2 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	1.8% 2/109 • Number of events 2 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Reproductive system and breast disorders PREMENSTRUAL DYSPHORIC DISORDER	0.67% 1/149 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/108 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Surgical and medical procedures ABORTION INDUCED	0.00% 0/149 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/138 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.93% 1/108 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.92% 1/109 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).

Other adverse events

Measure	Elagolix/Elagolix 150 mg QD n=149 participants at risk Participants were randomized to elagolix 150 mg once a day (QD) in pivotal Study M12-665 and continued to receive elagolix 150 mg QD for 6 months in this extension Study M12-667.	Elagolix/Elagolix 200 mg BID n=138 participants at risk Participants were randomized to elagolix 200 mg twice a day (BID) in pivotal Study M12-665 and continued to receive elagolix 200 mg BID for 6 months in this extension Study M12-667.	Placebo/Elagolix 150 mg QD n=108 participants at risk Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 150 mg QD for 6 months in this extension Study M12-667.	Placebo/Elagolix 200 mg BID n=109 participants at risk Participants who received placebo in pivotal Study M12-665 and were randomized to elagolix 200 mg BID for 6 months in this extension Study M12-667.
Gastrointestinal disorders ABDOMINAL PAIN	4.7% 7/149 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.8% 8/138 • Number of events 9 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	1.9% 2/108 • Number of events 3 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.92% 1/109 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Gastrointestinal disorders NAUSEA	4.7% 7/149 • Number of events 8 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	7.2% 10/138 • Number of events 12 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.6% 6/108 • Number of events 6 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	10.1% 11/109 • Number of events 12 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
General disorders FATIGUE	6.0% 9/149 • Number of events 9 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	3.6% 5/138 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/108 • Number of events 3 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	3.7% 4/109 • Number of events 4 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations BRONCHITIS	5.4% 8/149 • Number of events 8 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.1% 7/138 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/108 • Number of events 3 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/109 • Number of events 3 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations INFLUENZA	4.0% 6/149 • Number of events 6 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	4.3% 6/138 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	6.5% 7/108 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.92% 1/109 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations NASOPHARYNGITIS	6.0% 9/149 • Number of events 9 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	6.5% 9/138 • Number of events 11 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	4.6% 5/108 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/109 • Number of events 3 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations SINUSITIS	6.7% 10/149 • Number of events 10 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	7.2% 10/138 • Number of events 11 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.6% 6/108 • Number of events 6 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	9.2% 10/109 • Number of events 10 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	10.7% 16/149 • Number of events 18 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.9% 4/138 • Number of events 4 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	4.6% 5/108 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	4.6% 5/109 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations URINARY TRACT INFECTION	11.4% 17/149 • Number of events 23 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	8.0% 11/138 • Number of events 12 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	9.3% 10/108 • Number of events 10 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	7.3% 8/109 • Number of events 9 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Infections and infestations VULVOVAGINAL MYCOTIC INFECTION	5.4% 8/149 • Number of events 10 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	4.3% 6/138 • Number of events 6 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.6% 6/108 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/109 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Investigations BONE DENSITY DECREASED	1.3% 2/149 • Number of events 2 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	6.5% 9/138 • Number of events 9 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	1.9% 2/108 • Number of events 2 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/109 • Number of events 3 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Investigations C-REACTIVE PROTEIN INCREASED	2.0% 3/149 • Number of events 3 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.1% 7/138 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/108 • Number of events 4 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/109 • Number of events 4 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Musculoskeletal and connective tissue disorders ARTHRALGIA	1.3% 2/149 • Number of events 2 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.1% 7/138 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	1.9% 2/108 • Number of events 2 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	3.7% 4/109 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Musculoskeletal and connective tissue disorders BACK PAIN	4.0% 6/149 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	7.2% 10/138 • Number of events 11 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/108 • Number of events 3 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	4.6% 5/109 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Nervous system disorders HEADACHE	6.7% 10/149 • Number of events 11 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.8% 8/138 • Number of events 11 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	9.3% 10/108 • Number of events 13 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	13.8% 15/109 • Number of events 20 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders ANXIETY	3.4% 5/149 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	1.4% 2/138 • Number of events 2 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.6% 6/108 • Number of events 6 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.8% 3/109 • Number of events 4 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders DEPRESSION	5.4% 8/149 • Number of events 8 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	2.9% 4/138 • Number of events 4 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	1.9% 2/108 • Number of events 2 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.00% 0/109 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Psychiatric disorders INSOMNIA	3.4% 5/149 • Number of events 5 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	3.6% 5/138 • Number of events 6 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	0.93% 1/108 • Number of events 1 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.5% 6/109 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).
Vascular disorders HOT FLUSH	4.0% 6/149 • Number of events 7 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	5.8% 8/138 • Number of events 8 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	16.7% 18/108 • Number of events 19 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).	30.3% 33/109 • Number of events 38 • From the date of the first dose of study drug in Study M12-667 through up to 30 days after the last dose of study drug (up to 7 months).

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