Trial Outcomes & Findings for A Study to Evaluate Safety and Efficacy of Elagolix in Participants With Endometriosis With Associated Moderate to Severe Pain (NCT NCT03343067)

Results Overview

Proportion of responders at Month 6 based upon the scale for DYS pain scale (ranging from 0 \[none\] to 3 \[severe\]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

11 participants

Primary outcome timeframe

Month 6

Results posted on

2019-11-27

Participant Flow

The study was terminated early for business reasons, not for safety concerns. There are no subject data past Treatment Month 6.

Participant milestones

Participant milestones
Measure	Group A Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window
Open Label Period: Day 1 to Month 3 STARTED	7	3	1
Open Label Period: Day 1 to Month 3 COMPLETED	0	3	1
Open Label Period: Day 1 to Month 3 NOT COMPLETED	7	0	0
Double Blind Period: Month 3 to Month 6 STARTED	0	3	1
Double Blind Period: Month 3 to Month 6 COMPLETED	0	0	0
Double Blind Period: Month 3 to Month 6 NOT COMPLETED	0	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window
Double Blind Period: Month 3 to Month 6 Study Terminated by Sponsor	0	3	1

Baseline Characteristics

1 subject did not complete assessment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=7 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=3 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Total n=11 Participants Total of all reporting groups
Age, Customized 20 to < 25 years	1 Participants n=7 Participants	1 Participants n=3 Participants	0 Participants n=1 Participants	2 Participants n=11 Participants
Age, Customized 25 to < 30 years	0 Participants n=7 Participants	1 Participants n=3 Participants	0 Participants n=1 Participants	1 Participants n=11 Participants
Age, Customized 30 to < 35 years	1 Participants n=7 Participants	0 Participants n=3 Participants	1 Participants n=1 Participants	2 Participants n=11 Participants
Age, Customized 35 to < 40 years	1 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=1 Participants	1 Participants n=11 Participants
Age, Customized 40 to < 45 years	3 Participants n=7 Participants	1 Participants n=3 Participants	0 Participants n=1 Participants	4 Participants n=11 Participants
Age, Customized 45 to < 50 years	1 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=1 Participants	1 Participants n=11 Participants
Sex: Female, Male Female	7 Participants n=7 Participants	3 Participants n=3 Participants	1 Participants n=1 Participants	11 Participants n=11 Participants
Sex: Female, Male Male	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=1 Participants	0 Participants n=11 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=7 Participants	1 Participants n=3 Participants	1 Participants n=1 Participants	3 Participants n=11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=7 Participants	2 Participants n=3 Participants	0 Participants n=1 Participants	8 Participants n=11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=1 Participants	0 Participants n=11 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=1 Participants	0 Participants n=11 Participants
Race (NIH/OMB) Asian	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=1 Participants	0 Participants n=11 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=1 Participants	0 Participants n=11 Participants
Race (NIH/OMB) Black or African American	2 Participants n=7 Participants	1 Participants n=3 Participants	0 Participants n=1 Participants	3 Participants n=11 Participants
Race (NIH/OMB) White	5 Participants n=7 Participants	1 Participants n=3 Participants	0 Participants n=1 Participants	6 Participants n=11 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	1 Participants n=3 Participants	1 Participants n=1 Participants	2 Participants n=11 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=1 Participants	0 Participants n=11 Participants
Dysmenorrhea (DYS) Pain Scale	0.641 score on a scale STANDARD_DEVIATION 0.1689 • n=7 Participants	0.429 score on a scale STANDARD_DEVIATION 0.1030 • n=3 Participants	0.600 score on a scale STANDARD_DEVIATION NA • n=1 Participants	0.579 score on a scale STANDARD_DEVIATION 0.1696 • n=11 Participants
Non-Menstrual Pelvic Pain (NMPP) Pain Scale	1.053 score on a scale STANDARD_DEVIATION 0.4534 • n=7 Participants	0.914 score on a scale STANDARD_DEVIATION 0.4721 • n=3 Participants	2.400 score on a scale STANDARD_DEVIATION NA • n=1 Participants	1.138 score on a scale STANDARD_DEVIATION 0.5893 • n=11 Participants
Dyspareunia Pain Scale	0.539 score on a scale STANDARD_DEVIATION 0.9064 • n=7 Participants • 1 subject did not complete assessment	0.043 score on a scale STANDARD_DEVIATION 0.0202 • n=2 Participants • 1 subject did not complete assessment	3.000 score on a scale STANDARD_DEVIATION NA • n=1 Participants • 1 subject did not complete assessment	0.686 score on a scale STANDARD_DEVIATION 1.1187 • n=10 Participants • 1 subject did not complete assessment
Daily Diary Endometriosis-Associated Pain Score Via Numeric Rating Scale (NRS)	5.176 score on a scale STANDARD_DEVIATION 1.9302 • n=7 Participants	3.638 score on a scale STANDARD_DEVIATION 1.5692 • n=3 Participants	7.371 score on a scale STANDARD_DEVIATION NA • n=1 Participants	4.956 score on a scale STANDARD_DEVIATION 1.9663 • n=11 Participants
Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) NSAID	2.388 pills/day STANDARD_DEVIATION 2.7765 • n=7 Participants	0.581 pills/day STANDARD_DEVIATION 0.9330 • n=3 Participants	0.743 pills/day STANDARD_DEVIATION NA • n=1 Participants	1.745 pills/day STANDARD_DEVIATION 2.3655 • n=11 Participants
Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) Opioid	0.241 pills/day STANDARD_DEVIATION 0.3750 • n=7 Participants	0.057 pills/day STANDARD_DEVIATION 0.0990 • n=3 Participants	0.571 pills/day STANDARD_DEVIATION NA • n=1 Participants	0.221 pills/day STANDARD_DEVIATION 0.3270 • n=11 Participants
Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) NSAID + Opioid	2.629 pills/day STANDARD_DEVIATION 2.6903 • n=7 Participants	0.638 pills/day STANDARD_DEVIATION 0.8918 • n=3 Participants	1.314 pills/day STANDARD_DEVIATION NA • n=1 Participants	1.966 pills/day STANDARD_DEVIATION 2.3196 • n=11 Participants

PRIMARY outcome

Timeframe: Month 6

Population: Analysis was intended to be based on a receiver operating characteristic (ROC) threshold, which could not be calculated, since only 1 participant had a Month 6 assessment for this endpoint at the time of study termination.

Proportion of responders at Month 6 based upon the scale for DYS pain scale (ranging from 0 \[none\] to 3 \[severe\]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Month 6

Population: Analysis was intended to be based on ROC threshold, which could not be calculated, since only 1 participant had a Month 6 assessment for this endpoint at the time of study termination.

Proportion of responders at Month 6 based upon the scale for NMPP pain scale (ranging from 0 \[none\] to 3 \[severe\]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 0 (baseline), Month 6

Population: Participants with an assessment at baseline and given time point.

The DYS pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline in DYS at Month 6	—	-0.23 score on a scale Standard Deviation NA 1 participant analyzed	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Month 6

Population: Participants with an assessment at baseline and given time point.

The NMPP pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=2 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline in NMPP at Month 6	—	-0.13 score on a scale Standard Deviation 0.061	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Month 6

Population: Participants with an assessment at baseline and given time point.

The dyspareunia pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline in Dyspareunia at Month 6	—	0.29 score on a scale Standard Deviation NA 1 participant analyzed	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Month 6

Population: Participants with an assessment at baseline and given time point.

The NRS for overall endometriosis-associated pain ranges from 0 (none) to 10 (worst pain ever), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=2 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline in Daily Diary Endometriosis-Associated Pain Score Via Numeric Rating Scale (NRS) at Month 6	—	-1.36 score on a scale Standard Deviation 0.020	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Month 6

Population: Participants with an assessment at baseline and given time point.

Based on average pill counts and assessed using the daily e-Diary. Permitted non-steroidal anti-inflammatory drugs (NSAIDs) included naproxen, ibuprofen, diclofenac, and celecoxib. Permitted opioids included hydrocodone + acetaminophen and codeine phosphate + acetaminophen.

Outcome measures

Outcome measures
Measure	Group A Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=2 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline in Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) at Month 6 NSAID: Change at Month 6	—	0.63 pills/day Standard Deviation 0.606	—
Change From Baseline in Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) at Month 6 Opioid: Change at Month 6	—	0.09 pills/day Standard Deviation 0.121	—
Change From Baseline in Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) at Month 6 NSAID + Opioid: Change at Month 6	—	0.71 pills/day Standard Deviation 0.485	—

SECONDARY outcome

Timeframe: Month 6

Population: Participants with both baseline and post-baseline values for Daily Diary Endometriosis-Associated Pain Score via NRS.

The NRS for overall endometriosis-associated pain ranges from 0 (none) to 10 (worst pain ever), recorded in a daily eDiary and averaged monthly based on a 35-day window.

Outcome measures

Outcome measures
Measure	Group A Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=2 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Percentage of Participants With 30% or More Reduction From Baseline Based on the 35 Day Mean of the Daily Diary Endometriosis-Associated Pain Score Via NRS at Month 6	—	50.0 percentage of participants	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Analysis was intended to be based on ROC threshold, which could not be calculated for this endpoint due to low enrollment at the time of study termination.

As assessed by change and percent change from baseline in average pain score and rescue analgesic use monthly for DYS, NMPP, dyspareunia, and Daily Diary endometriosis-associated pain score via NRS, respectively.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Analysis was intended to be based on ROC threshold, which could not be calculated for this endpoint due to low enrollment at the time of study termination.

As assessed by change and percent change from Baseline in average pain score and rescue analgesic use monthly for DYS, NMPP, dyspareunia, and Daily Diary endometriosis-associated pain score via NRS, respectively.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

The DYS pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement. The analysis was based on a 28-day window. If a participant prematurely discontinued during the open-label period, based on the analysis window, some data might fall into Month 4 analysis.

Outcome measures

Outcome measures
Measure	Group A n=6 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=2 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline Over Time in Monthly Average DYS Pain Score Change at Month 1	0.05 score on a scale Standard Deviation 0.655	-0.04 score on a scale Standard Deviation NA 1 participant analyzed	—
Change From Baseline Over Time in Monthly Average DYS Pain Score Change at Month 2	-0.18 score on a scale Standard Deviation 0.124	-0.26 score on a scale Standard Deviation NA 1 participant analyzed	—
Change From Baseline Over Time in Monthly Average DYS Pain Score Change at Month 3	-0.50 score on a scale Standard Deviation 0.263	-0.34 score on a scale Standard Deviation NA 1 participant analyzed	—
Change From Baseline Over Time in Monthly Average DYS Pain Score Change at Month 4	-0.69 score on a scale Standard Deviation NA 1 participant analyzed	-0.06 score on a scale Standard Deviation NA 1 participant analyzed	—
Change From Baseline Over Time in Monthly Average DYS Pain Score Change at Month 5	—	-0.16 score on a scale Standard Deviation 0.141	—
Change From Baseline Over Time in Monthly Average DYS Pain Score Change at Month 6	—	-0.23 score on a scale Standard Deviation NA 1 participant analyzed	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

The NMPP pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A n=6 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=3 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline Over Time in Monthly Average NMPP Pain Score Change at Month 1	-0.13 score on a scale Standard Deviation 0.252	-0.07 score on a scale Standard Deviation 0.508	0.39 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average NMPP Pain Score Change at Month 2	-0.48 score on a scale Standard Deviation 0.394	-0.30 score on a scale Standard Deviation 0.167	0.29 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average NMPP Pain Score Change at Month 3	-0.70 score on a scale Standard Deviation 0.828	-0.30 score on a scale Standard Deviation 0.092	0.54 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average NMPP Pain Score Change at Month 4	-1.34 score on a scale Standard Deviation NA 1 participant analyzed	-0.34 score on a scale Standard Deviation 0.029	0.46 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average NMPP Pain Score Change at Month 5	—	-0.27 score on a scale Standard Deviation 0.256	—
Change From Baseline Over Time in Monthly Average NMPP Pain Score Change at Month 6	—	-0.13 score on a scale Standard Deviation 0.061	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

The dyspareunia pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A n=4 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=2 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score Change at Month 3	-2.20 score on a scale Standard Deviation NA 1 participant analyzed	0.07 score on a scale Standard Deviation 0.101	-0.03 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score Change at Month 4	-2.23 score on a scale Standard Deviation NA 1 participant analyzed	0.09 score on a scale Standard Deviation 0.040	-0.03 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score Change at Month 5	—	0.09 score on a scale Standard Deviation 0.081	—
Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score Change at Month 6	—	0.29 score on a scale Standard Deviation NA 1 participant analyzed	—
Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score Change at Month 1	-0.50 score on a scale Standard Deviation 0.741	0.30 score on a scale Standard Deviation NA 1 participant analyzed	-0.29 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score Change at Month 2	-1.44 score on a scale Standard Deviation 1.071	0.06 score on a scale Standard Deviation NA 1 participant analyzed	-0.37 score on a scale Standard Deviation NA 1 participant analyzed

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

The NRS for overall endometriosis-associated pain ranges from 0 (none) to 10 (worst pain ever), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A n=7 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=3 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS Change at Month 1	-0.86 score on a scale Standard Deviation 1.975	-0.89 score on a scale Standard Deviation 1.159	-0.84 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS Change at Month 2	-2.40 score on a scale Standard Deviation 2.106	-2.02 score on a scale Standard Deviation 0.758	-1.40 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS Change at Month 3	-3.70 score on a scale Standard Deviation 3.616	-1.81 score on a scale Standard Deviation 0.430	-1.34 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS Change at Month 4	-6.43 score on a scale Standard Deviation NA 1 participant analyzed	-1.43 score on a scale Standard Deviation 1.078	-1.06 score on a scale Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS Change at Month 5	—	-1.40 score on a scale Standard Deviation 0.961	—
Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS Change at Month 6	—	-1.36 score on a scale Standard Deviation 0.020	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

The DYS pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A n=6 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=2 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Percent Change From Baseline to Each Month During the Treatment Period for DYS Percent Change at Month 4	-80.00 percent change of units on a scale Standard Deviation NA 1 participant analyzed	-16.67 percent change of units on a scale Standard Deviation NA 1 participant analyzed	—
Percent Change From Baseline to Each Month During the Treatment Period for DYS Percent Change at Month 5	—	-40.48 percent change of units on a scale Standard Deviation 33.672	—
Percent Change From Baseline to Each Month During the Treatment Period for DYS Percent Change at Month 6	—	-57.14 percent change of units on a scale Standard Deviation NA 1 participant analyzed	—
Percent Change From Baseline to Each Month During the Treatment Period for DYS Percent Change at Month 1	1.67 percent change of units on a scale Standard Deviation 109.961	-7.89 percent change of units on a scale Standard Deviation NA 1 participant analyzed	—
Percent Change From Baseline to Each Month During the Treatment Period for DYS Percent Change at Month 2	-27.45 percent change of units on a scale Standard Deviation 17.119	-75.00 percent change of units on a scale Standard Deviation NA 1 participant analyzed	—
Percent Change From Baseline to Each Month During the Treatment Period for DYS Percent Change at Month 3	-62.92 percent change of units on a scale Standard Deviation 24.159	-85.71 percent change of units on a scale Standard Deviation NA 1 participant analyzed	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

The NMPP pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A n=6 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=3 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Percent Change From Baseline to Each Month During the Treatment Period for NMPP Percent Change at Month 5	—	-28.40 percentage change of units on a scale Standard Deviation 33.641	—
Percent Change From Baseline to Each Month During the Treatment Period for NMPP Percent Change at Month 1	-11.81 percentage change of units on a scale Standard Deviation 26.677	4.22 percentage change of units on a scale Standard Deviation 53.238	16.07 percentage change of units on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for NMPP Percent Change at Month 2	-37.53 percentage change of units on a scale Standard Deviation 31.150	-34.21 percentage change of units on a scale Standard Deviation 18.044	11.90 percentage change of units on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for NMPP Percent Change at Month 3	-38.26 percentage change of units on a scale Standard Deviation 42.319	-38.03 percentage change of units on a scale Standard Deviation 20.343	22.62 percentage change of units on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for NMPP Percent Change at Month 4	-71.21 percentage change of units on a scale Standard Deviation NA 1 participant analyzed	-44.49 percentage change of units on a scale Standard Deviation 20.725	19.05 percentage change of units on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for NMPP Percent Change at Month 6	—	-17.23 percentage change of units on a scale Standard Deviation 16.044	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

The dyspareunia pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A n=7 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=3 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia Percent Change at Month 6	—	-18.08 percentage change of units on a scale Standard Deviation 25.571	—
Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia Percent Change at Month 1	0.14 percentage change of units on a scale Standard Deviation 18.180	-15.27 percentage change of units on a scale Standard Deviation 26.791	-9.52 percentage change of units on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia Percent Change at Month 2	6.60 percentage change of units on a scale Standard Deviation 15.719	-15.26 percentage change of units on a scale Standard Deviation 21.840	-12.38 percentage change of units on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia Percent Change at Month 3	60.88 percentage change of units on a scale Standard Deviation 65.632	-21.63 percentage change of units on a scale Standard Deviation 24.719	-0.95 percentage change of units on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia Percent Change at Month 4	106.25 percentage change of units on a scale Standard Deviation NA 1 participant analyzed	-12.67 percentage change of units on a scale Standard Deviation 20.433	-0.95 percentage change of units on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia Percent Change at Month 5	—	-14.86 percentage change of units on a scale Standard Deviation 16.002	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

The NRS for overall endometriosis-associated pain ranges from 0 (none) to 10 (worst pain ever), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Group A n=7 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=3 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS Percent Change at Month 1	-14.10 percentage change of score on a scale Standard Deviation 37.146	-19.61 percentage change of score on a scale Standard Deviation 35.468	-11.34 percentage change of score on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS Percent Change at Month 2	-37.82 percentage change of score on a scale Standard Deviation 18.066	-56.25 percentage change of score on a scale Standard Deviation 4.507	-18.99 percentage change of score on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS Percent Change at Month 3	-43.98 percentage change of score on a scale Standard Deviation 35.509	-53.05 percentage change of score on a scale Standard Deviation 13.803	-18.22 percentage change of score on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS Percent Change at Month 4	-70.98 percentage change of score on a scale Standard Deviation NA 1 participant analyzed	-38.00 percentage change of score on a scale Standard Deviation 31.275	-14.34 percentage change of score on a scale Standard Deviation NA 1 participant analyzed
Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS Percent Change at Month 5	—	-35.81 percentage change of score on a scale Standard Deviation 9.326	—
Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS Percent Change at Month 6	—	-33.56 percentage change of score on a scale Standard Deviation 11.357	—

SECONDARY outcome

Timeframe: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Population: Participants with an assessment at baseline and given time point.

Based on average pill counts and assessed using a daily e-Diary. Permitted non-steroidal anti-inflammatory drugs (NSAIDs) included naproxen, ibuprofen, diclofenac, and celecoxib. Permitted opioids included hydrocodone + acetaminophen and codeine phosphate + acetaminophen.

Outcome measures

Outcome measures
Measure	Group A n=7 Participants Day 1 through Month 3 (open-label): elagolix 150 mg QD Participants discontinued prematurely during the open-label period.	Group B n=3 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Efficacy responders to elagolix 150 mg QD Month 3 continued on elagolix 150 mg QD The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via a Numeric Rating Scale (NRS) in the electronic diary. Efficacy responder: ≥ 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.	Group C n=1 Participants Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group The efficacy responder status of each participant was determined based on the responses to the Daily Diary endometriosis-associated pain score via NRS in the electronic diary. Incomplete efficacy responder: \< 30% decrease (improvement) from Baseline based on the average of the Daily Diary for endometriosis-associated pain score via NRS over a 35 day window.
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID: Change at Month 1	-0.84 pills/day Standard Deviation 0.796	0.09 pills/day Standard Deviation 0.388	-0.67 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID: Change at Month 2	-1.15 pills/day Standard Deviation 0.785	-0.17 pills/day Standard Deviation 0.834	0.63 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID: Change at Month 3	-0.96 pills/day Standard Deviation 1.030	-0.43 pills/day Standard Deviation 1.091	-0.71 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID: Change at Month 4	-1.69 pills/day Standard Deviation NA 1 participant analyzed	0.01 pills/day Standard Deviation 0.845	-0.63 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID: Change at Month 5	—	0.23 pills/day Standard Deviation 1.197	—
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID: Change at Month 6	—	0.63 pills/day Standard Deviation 0.606	—
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics Opioid: Change at Month 1	0.12 pills/day Standard Deviation 0.552	-0.06 pills/day Standard Deviation 0.099	-0.43 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics Opioid: Change at Month 2	-0.17 pills/day Standard Deviation 0.263	-0.03 pills/day Standard Deviation 0.049	-0.51 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics Opioid: Change at Month 3	-0.17 pills/day Standard Deviation 0.242	0.02 pills/day Standard Deviation 0.016	-0.49 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics Opioid: Change at Month 4	-0.34 pills/day Standard Deviation NA 1 participant analyzed	-0.01 pills/day Standard Deviation 0.044	-0.40 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics Opioid: Change at Month 5	—	-0.05 pills/day Standard Deviation 0.082	—
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics Opioid: Change at Month 6	—	0.09 pills/day Standard Deviation 0.121	—
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID + Opioid: Change at Month 1	-0.72 pills/day Standard Deviation 1.178	0.03 pills/day Standard Deviation 0.436	-1.10 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID + Opioid: Change at Month 2	-1.33 pills/day Standard Deviation 0.767	-0.20 pills/day Standard Deviation 0.830	-1.14 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID + Opioid: Change at Month 3	-1.13 pills/day Standard Deviation 1.273	-0.41 pills/day Standard Deviation 1.107	-1.20 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID + Opioid: Change at Month 4	-2.03 pills/day Standard Deviation NA 1 participant analyzed	-0.00 pills/day Standard Deviation 0.863	-1.03 pills/day Standard Deviation NA 1 participant analyzed
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID + Opioid: Change at Month 5	—	0.18 pills/day Standard Deviation 1.217	—
Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics NSAID + Opioid: Change at Month 6	—	0.71 pills/day Standard Deviation 0.485	—

SECONDARY outcome

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

Based only on reduction of rescue analgesics used. Responders were defined as: * participants with no analgesic use at screening and no analgesic use added * participants with NSAID only use at screening and NSAID dose stopped, decreased, or stable (\<15% increase) and no opioid use added * participants with opioid only use at screening and opioid dose stopped, decreased, or stable (\<15% increase), opioid dose stopped and NSAID substituted (any dose), opioid dose decreased and NSAID added (any dose) * participants with NSAID + opioid use at screening and any of the following: NSAID dose stopped + opioid analgesic use stopped, decreased, or stable (\<15% increase); NSAID dose decreased + opioid analgesic use stopped, decreased, or stable (\<15% increase); NSAID dose stable (\< 15% increase) + opioid analgesic use stopped, decreased, or stable (\<15% increase); NSAID dose increased by \>15% + opioid analgesic use stopped; NSAID dose increased by \>15% + opioid analgesic dose decreases.