Trial Outcomes & Findings for SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated Pain (NCT NCT03654274)

Last Updated: 2023-08-08

Results Overview

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for dysmenorrhea declined from baseline to Week 52 by at least 2.8 points without increased use of protocol-specified analgesics for pelvic pain at Week 52 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

802 participants

Primary outcome timeframe

Week 52

Results posted on

2023-08-08

Participant Flow

All participants who completed their participation in one of the pivotal studies (MVT-601-3101 or MVT-601-3102) were eligible to enroll in this study.

The study results were presented by pivotal study treatment but all the participants only received relugolix plus Estradiol (E2)/Norethindrone Acetate (NETA).

Participant milestones

Participant milestones
Measure	Relugolix Plus E2/NETA (Group A) Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Overall Study STARTED	278	247	277
Overall Study Received at Least 1 Dose of Study Drug	277	247	275
Overall Study COMPLETED	172	155	174
Overall Study NOT COMPLETED	106	92	103

Reasons for withdrawal

Reasons for withdrawal
Measure	Relugolix Plus E2/NETA (Group A) Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Overall Study Adverse Event	19	23	24
Overall Study Protocol Deviation	0	2	0
Overall Study Lost to Follow-up	8	6	5
Overall Study Withdrawal by Subject	46	25	33
Overall Study Lack of Efficacy	4	5	7
Overall Study Pregnancy	2	2	1
Overall Study Other	27	29	32
Overall Study Participants Who Consented to Week 52 and Completed at Week 52	0	0	1

Baseline Characteristics

SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Relugolix Plus E2/NETA (Group A) n=277 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=247 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=275 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Total n=799 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	277 Participants n=5 Participants	247 Participants n=7 Participants	275 Participants n=5 Participants	799 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	277 Participants n=5 Participants	247 Participants n=7 Participants	275 Participants n=5 Participants	799 Participants n=4 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
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants	31 Participants n=7 Participants	42 Participants n=5 Participants	100 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	249 Participants n=5 Participants	215 Participants n=7 Participants	233 Participants n=5 Participants	697 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	17 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants	37 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White	254 Participants n=5 Participants	236 Participants n=7 Participants	248 Participants n=5 Participants	738 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	4 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	48 participants n=5 Participants	44 participants n=7 Participants	52 participants n=5 Participants	144 participants n=4 Participants
Region of Enrollment Argentina	10 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	34 participants n=4 Participants
Region of Enrollment Australia	2 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Belgium	3 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Brazil	13 participants n=5 Participants	13 participants n=7 Participants	15 participants n=5 Participants	41 participants n=4 Participants
Region of Enrollment Bulgaria	14 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants	29 participants n=4 Participants
Region of Enrollment Canada	0 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment Chile	3 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Czechia	12 participants n=5 Participants	8 participants n=7 Participants	8 participants n=5 Participants	28 participants n=4 Participants
Region of Enrollment Finland	2 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Georgia	5 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	7 participants n=4 Participants
Region of Enrollment Hungary	7 participants n=5 Participants	10 participants n=7 Participants	7 participants n=5 Participants	24 participants n=4 Participants
Region of Enrollment Italy	7 participants n=5 Participants	8 participants n=7 Participants	2 participants n=5 Participants	17 participants n=4 Participants
Region of Enrollment New Zealand	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Poland	105 participants n=5 Participants	86 participants n=7 Participants	106 participants n=5 Participants	297 participants n=4 Participants
Region of Enrollment Portugal	1 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	7 participants n=4 Participants
Region of Enrollment Romania	12 participants n=5 Participants	12 participants n=7 Participants	7 participants n=5 Participants	31 participants n=4 Participants
Region of Enrollment South Africa	8 participants n=5 Participants	10 participants n=7 Participants	14 participants n=5 Participants	32 participants n=4 Participants
Region of Enrollment Spain	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Ukraine	23 participants n=5 Participants	20 participants n=7 Participants	20 participants n=5 Participants	63 participants n=4 Participants
Time Since Surgical Diagnosis of Endometriosis	4.0 years STANDARD_DEVIATION 3.52 • n=5 Participants	4.7 years STANDARD_DEVIATION 4.00 • n=7 Participants	3.9 years STANDARD_DEVIATION 3.24 • n=5 Participants	4.2 years STANDARD_DEVIATION 3.60 • n=4 Participants
Dysmenorrhea Numerical Rating Scale (NRS) Score at Baseline	7.1 score on a scale STANDARD_DEVIATION 1.66 • n=5 Participants	7.0 score on a scale STANDARD_DEVIATION 1.65 • n=7 Participants	7.2 score on a scale STANDARD_DEVIATION 1.63 • n=5 Participants	7.1 score on a scale STANDARD_DEVIATION 1.65 • n=4 Participants
Nonmenstrual Pelvic Pain (NMPP) NRS Score at Baseline	5.7 score on a scale STANDARD_DEVIATION 1.93 • n=5 Participants	5.5 score on a scale STANDARD_DEVIATION 1.98 • n=7 Participants	5.7 score on a scale STANDARD_DEVIATION 1.91 • n=5 Participants	5.6 score on a scale STANDARD_DEVIATION 1.94 • n=4 Participants
Bone Mineral Density (BMD) Lumbar Spine L1-L4	1.14 g/cm^2 STANDARD_DEVIATION 0.163 • n=5 Participants	1.14 g/cm^2 STANDARD_DEVIATION 0.144 • n=7 Participants	1.14 g/cm^2 STANDARD_DEVIATION 0.149 • n=5 Participants	1.14 g/cm^2 STANDARD_DEVIATION 0.153 • n=4 Participants
BMD Total Hip	0.98 g/cm^2 STANDARD_DEVIATION 0.133 • n=5 Participants	0.97 g/cm^2 STANDARD_DEVIATION 0.120 • n=7 Participants	0.98 g/cm^2 STANDARD_DEVIATION 0.123 • n=5 Participants	0.97 g/cm^2 STANDARD_DEVIATION 0.126 • n=4 Participants
BMD Femoral Neck	0.93 g/cm^2 STANDARD_DEVIATION 0.157 • n=5 Participants	0.92 g/cm^2 STANDARD_DEVIATION 0.136 • n=7 Participants	0.93 g/cm^2 STANDARD_DEVIATION 0.151 • n=5 Participants	0.92 g/cm^2 STANDARD_DEVIATION 0.149 • n=4 Participants

PRIMARY outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled into MVT-601-3103 study and received any amount of open-label study drug in MVT-601-3103 study. Study results are reported by pivotal study treatment, but all participants only received relugolix plus E2/NETA.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=277 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=247 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=275 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 52	84.8 percentage of participants Interval 80.06 to 88.85	82.2 percentage of participants Interval 76.83 to 86.75	75.6 percentage of participants Interval 70.12 to 80.59

PRIMARY outcome

Timeframe: Week 52

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for NMPP declined from baseline to Week 52 by at least 2.1 points without increased use of protocol-specified analgesics for pelvic pain at Week 52 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=277 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=247 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=275 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 52	73.6 percentage of participants Interval 68.04 to 78.74	70.4 percentage of participants Interval 64.33 to 76.06	68.0 percentage of participants Interval 62.13 to 73.47

PRIMARY outcome

Timeframe: Week 104

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for dysmenorrhea declined from baseline to Week 104 by at least 2.8 points without increased use of protocol-specified analgesics for pelvic pain at Week 104 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=277 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=247 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=275 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 104	84.8 percentage of participants Interval 80.06 to 88.85	83.0 percentage of participants Interval 77.72 to 87.46	80.4 percentage of participants Interval 75.17 to 84.89

PRIMARY outcome

Timeframe: Week 104

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for NMPP declined from baseline to Week 104 by at least 2.1 points without increased use of protocol-specified analgesics for pelvic pain at Week 104 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=277 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=247 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=275 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 104	75.8 percentage of participants Interval 70.33 to 80.74	71.7 percentage of participants Interval 65.6 to 77.19	73.1 percentage of participants Interval 67.44 to 78.24

SECONDARY outcome

Timeframe: Week 52

Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain. The least squares (LS) mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=232 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=207 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=229 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 52	-37.7 score on a scale Standard Error 1.34	-36.1 score on a scale Standard Error 1.37	-35.1 score on a scale Standard Error 1.32

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=167 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=151 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=173 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 104	-41.3 score on a scale Standard Error 1.33	-38.9 score on a scale Standard Error 1.36	-37.7 score on a scale Standard Error 1.29

SECONDARY outcome

Timeframe: Week 52

Assessed using the Pain Domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=232 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=207 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=229 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain Scores From The Pivotal Phase 3 Study Baseline At Week 52	83.6 percentage of participants Interval 78.22 to 88.14	81.2 percentage of participants Interval 75.16 to 86.25	79.5 percentage of participants Interval 73.66 to 84.51

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=167 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=151 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=173 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain Scores From The Pivotal Phase 3 Study Baseline At Week 104	88.6 percentage of participants Interval 82.8 to 93.01	85.4 percentage of participants Interval 78.78 to 90.64	86.1 percentage of participants Interval 80.06 to 90.9

SECONDARY outcome

Timeframe: Week 52

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=235 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=204 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=233 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 52	-5.9 score on a scale Standard Error 0.15	-5.7 score on a scale Standard Error 0.16	-5.3 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=129 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=112 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=124 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 104	-5.9 score on a scale Standard Error 0.17	-5.7 score on a scale Standard Error 0.18	-5.6 score on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Week 52

The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participant's impression of change in the severity of pain during their menstrual cycle. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=221 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=202 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=230 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 52	89.1 percentage of participants Interval 84.27 to 92.92	87.1 percentage of participants Interval 81.71 to 91.42	83.0 percentage of participants Interval 77.56 to 87.66

SECONDARY outcome

Timeframe: Week 52

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=235 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=204 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=233 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 52	-3.6 score on a scale Standard Error 0.15	-3.4 score on a scale Standard Error 0.16	-3.4 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=129 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=112 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=124 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 104	-4.0 score on a scale Standard Error 0.16	-3.5 score on a scale Standard Error 0.17	-3.8 score on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Week 52

Assessed using an NRS score (11-point scale) for overall pain recorded daily in an electronic diary. Participants rated their overall pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=235 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=204 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=233 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 52	-3.9 score on a scale Standard Error 0.15	-3.6 score on a scale Standard Error 0.16	-3.6 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=129 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=112 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=124 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 104	-4.2 score on a scale Standard Error 0.16	-3.9 score on a scale Standard Error 0.17	-4.0 score on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Week 104

Assessed based on usage of study-specified opioids for endometriosis-associated pain recorded daily in an electronic diary. Participants received protocol-specified opioids for treatment of endometriosis-associated pain as needed for pain but not prophylactically.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=277 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=247 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=275 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Not Using Opioids For Endometriosis-associated Pain At Week 104	91.0 percentage of participants Interval 87.0 to 94.1	88.3 percentage of participants Interval 83.6 to 92.0	90.5 percentage of participants Interval 86.5 to 93.7

SECONDARY outcome

Timeframe: Week 104

Assessed based on usage of study-specified analgesics for endometriosis-associated pain recorded daily in an electronic diary. Participants received protocol-specified analgesics for treatment of endometriosis-associated pain as needed for pain but not prophylactically.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=277 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=247 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=275 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Not Using Analgesics For Endometriosis-associated Pain At Week 104	75.1 percentage of participants Interval 69.6 to 80.1	76.5 percentage of participants Interval 70.7 to 81.7	76.0 percentage of participants Interval 70.5 to 80.9

SECONDARY outcome

Timeframe: Week 52

The PGIC for NMPP is a 1-item questionnaire designed to assess participant's impression of change in the severity of pain when they are not menstruating. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=221 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=202 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=230 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 52	85.5 percentage of participants Interval 80.18 to 89.88	86.1 percentage of participants Interval 80.59 to 90.59	79.1 percentage of participants Interval 73.3 to 84.19

SECONDARY outcome

Timeframe: Week 52

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants were to report whether they had vaginal sexual intercourse and rated their level of pelvic pain during intercourse on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=151 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=126 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=140 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 52	-3.3 score on a scale Standard Error 0.18	-3.0 score on a scale Standard Error 0.19	-3.0 score on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=79 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=61 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=69 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 104	-3.5 score on a scale Standard Error 0.21	-2.9 score on a scale Standard Error 0.22	-3.4 score on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Week 52

The PGIC for dyspareunia is a 1-item questionnaire designed to assess participant's impression of change in the severity of their pain during sexual intercourse. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=210 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=194 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=210 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 52	61.0 percentage of participants Interval 54.0 to 67.59	61.9 percentage of participants Interval 54.62 to 68.72	60.0 percentage of participants Interval 53.03 to 66.68

SECONDARY outcome

Timeframe: Week 52

Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an electronic diary. Participants were to report their pain during intercourse daily using the following response options: Severe (avoids intercourse because of pain), Moderate (intercourse painful to the point of causing interruption), Mild (tolerated pain), No pain (no pain during intercourse), or No intercourse (no intercourse for other reasons). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=174 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=143 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=160 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 52	-0.9 score on a scale Standard Error 0.06	-0.9 score on a scale Standard Error 0.06	-0.8 score on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=90 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=68 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=73 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 104	-1.0 score on a scale Standard Error 0.06	-0.9 score on a scale Standard Error 0.07	-1.0 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Week 52

The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant's impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=232 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=206 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=226 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 52	-1.3 score on a scale Standard Error 0.06	-1.2 score on a scale Standard Error 0.06	-1.2 score on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=159 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=146 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=168 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 104	-1.4 score on a scale Standard Error 0.07	-1.4 score on a scale Standard Error 0.07	-1.3 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Week 52

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=232 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=206 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=226 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 52 Improvement (-1 to -4)	81.5 percentage of participants	69.9 percentage of participants	72.6 percentage of participants
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 52 No Change (0)	14.7 percentage of participants	26.2 percentage of participants	23.0 percentage of participants
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 52 Deterioration (+1 to +4)	3.9 percentage of participants	3.9 percentage of participants	4.4 percentage of participants

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=159 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=146 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=168 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 104 Improvement (-1 to -4)	85.5 percentage of participants	82.2 percentage of participants	80.4 percentage of participants
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 104 No Change (0)	13.8 percentage of participants	15.8 percentage of participants	16.7 percentage of participants
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 104 Deterioration (+1 to +4)	0.6 percentage of participants	2.1 percentage of participants	3.0 percentage of participants

SECONDARY outcome

Timeframe: Week 52

The PGA for functional impairment is a 1-item questionnaire designed to assess participant's impression of how their pain affected their usual activities. The participants responded to the question: "How much were your daily activities limited by endometriosis over the last 4 weeks?" using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4). The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=235 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=206 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=230 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 52	-1.6 score on a scale Standard Error 0.06	-1.6 score on a scale Standard Error 0.06	-1.6 score on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=164 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=150 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=170 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 104	-1.9 score on a scale Standard Error 0.07	-1.9 score on a scale Standard Error 0.07	-1.8 score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Week 52

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=235 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=206 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=230 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 52 Improvement (-1 to -4)	88.9 percentage of participants	86.9 percentage of participants	86.1 percentage of participants
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 52 No Change (0)	8.1 percentage of participants	12.6 percentage of participants	10.0 percentage of participants
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 52 Deterioration (+1 to +4)	3.0 percentage of participants	0.5 percentage of participants	3.9 percentage of participants

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=164 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=150 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=170 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 104 Improvement (-1 to -4)	92.7 percentage of participants	92.0 percentage of participants	91.2 percentage of participants
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 104 No Change (0)	6.7 percentage of participants	7.3 percentage of participants	8.8 percentage of participants
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 104 Deterioration (+1 to +4)	0.6 percentage of participants	0.7 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Week 52

Assessed using the following non-pain domains of the EHP-30 questionnaire: Control and Powerlessness (questions 12 through 17), Emotional Well-Being (questions 18 through 23), Social Support (questions 24 through 27), and Self-Image (questions 28 through 30). The score for each domain ranged from 0 to 100. Higher scores represent a greater impact of endometriosis. The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=232 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=207 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=229 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 52 Control and Powerlessness	-43.7 score on a scale Standard Error 1.61	-40.1 score on a scale Standard Error 1.66	-39.5 score on a scale Standard Error 1.59
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 52 Emotional Well-being	-26.7 score on a scale Standard Error 1.51	-24.4 score on a scale Standard Error 1.56	-23.7 score on a scale Standard Error 1.49
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 52 Social Support	-28.8 score on a scale Standard Error 1.69	-28.9 score on a scale Standard Error 1.74	-28.7 score on a scale Standard Error 1.67
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 52 Self Image	-26.4 score on a scale Standard Error 1.70	-23.1 score on a scale Standard Error 1.75	-22.8 score on a scale Standard Error 1.68

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=167 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=151 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=173 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 104 Social Support	-33.2 score on a scale Standard Error 1.85	-24.9 score on a scale Standard Error 1.90	-29.7 score on a scale Standard Error 1.80
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 104 Control and Powerlessness	-47.5 score on a scale Standard Error 1.59	-43.7 score on a scale Standard Error 1.63	-41.9 score on a scale Standard Error 1.54
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 104 Emotional Well-being	-30.7 score on a scale Standard Error 1.60	-26.5 score on a scale Standard Error 1.65	-25.6 score on a scale Standard Error 1.56
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 104 Self Image	-29.5 score on a scale Standard Error 1.88	-25.8 score on a scale Standard Error 1.94	-25.2 score on a scale Standard Error 1.83

SECONDARY outcome

Timeframe: Week 52

Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an electronic diary. Participants were to report their pain as related to functional impairment daily in an electronic diary using the following response options: Severe (in bed all day, incapacitation), Moderate (in bed part of the day, some loss of work efficiency), Mild (some loss of work efficiency), No pain (no pain associated with menstruation during past 24 hours), or did not menstruate during the past 24 hours. Participants gave a possible score of 0 (no pain) to 4 (did not menstruate). The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=235 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=204 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=233 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 52	-1.3 score on a scale Standard Error 0.04	-1.3 score on a scale Standard Error 0.04	-1.2 score on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=129 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=112 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=124 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 104	-1.3 score on a scale Standard Error 0.04	-1.3 score on a scale Standard Error 0.05	-1.2 score on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Week 52

Assessed using the participant-modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an electronic diary. Participants reported their pain daily in an electronic diary using the following response options: Severe (requires strong analgesics), Moderate (noticeable pelvic pain), Mild (occasional pelvic pain), or No pain (no pain during past 24 hours). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=235 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=204 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=233 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 52	-1.0 score on a scale Standard Error 0.04	-1.0 score on a scale Standard Error 0.05	-1.0 score on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Week 104

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=129 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=112 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=124 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 104	-1.2 score on a scale Standard Error 0.05	-1.1 score on a scale Standard Error 0.05	-1.1 score on a scale Standard Error 0.05

SECONDARY outcome

Timeframe: Week 52

Population: Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix plus E2/NETA. The number analyzed represents the proportion of the overall number of participants analyzed with values at that time point.

Assessed by dual-energy X-ray absorptiometry (DXA) scan at lumbar spine, total hip, and femoral neck (same leg for each participant) at each designated time point. All participants who completed treatment or terminated from the study early were required to return for a 6-month post-treatment follow-up (PTFU) and a 12-month PTFU DXA scan (except if participant was beyond 14 months from last day on treatment). Participants were also to have clinical laboratory evaluations (vitamin D, thyroid stimulating hormone, parathyroid hormone, creatinine, calcium, and phosphorous) at the 6-month and 12-month PTFU only if the PTFU DXA scans showed a bone loss of ≥3% at the lumbar spine and/or total hip compared with the parent study baseline.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=233 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=205 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=232 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 Lumbar Spine (L1-L4)	-0.69 percent change Standard Error 0.241	-1.09 percent change Standard Error 0.256	-0.09 percent change Standard Error 0.244
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 Femoral Neck	-0.21 percent change Standard Error 0.277	-0.84 percent change Standard Error 0.294	0.06 percent change Standard Error 0.280
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 Total Hip	-0.10 percent change Standard Error 0.207	-0.52 percent change Standard Error 0.219	0.27 percent change Standard Error 0.210

SECONDARY outcome

Timeframe: Week 104

Population: Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix plus E2/NETA. The overall number of participants analyzed represents the number of participants evaluable at that time point.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=163 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=150 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=173 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 104 Lumbar Spine (L1-L4)	-0.45 percent change Standard Error 0.295	-0.56 percent change Standard Error 0.310	-0.09 percent change Standard Error 0.292
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 104 Femoral Neck	0.24 percent change Standard Error 0.325	-0.44 percent change Standard Error 0.341	-0.05 percent change Standard Error 0.324
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 104 Total Hip	0.82 percent change Standard Error 0.268	0.10 percent change Standard Error 0.281	0.69 percent change Standard Error 0.267

SECONDARY outcome

Timeframe: Week 52

Population: Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA. The number of participants analyzed represents the proportion of the participants with values at that time point.

Blood samples were collected from participants for estradiol measurements at each specified timepoints. Estradiol concentrations were measured using an immuno-enzymatic assay based on a commercially available kit.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=210 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=185 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=201 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 52	-55.22 pg/mL Standard Deviation 99.636	-77.76 pg/mL Standard Deviation 125.791	-62.07 pg/mL Standard Deviation 90.031

SECONDARY outcome

Timeframe: Week 104

Population: Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA. The number of participants analyzed represents the proportion of the participants with values at that time point.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=148 Participants Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=133 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=157 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 104	-51.72 pg/mL Standard Deviation 106.801	-74.68 pg/mL Standard Deviation 138.840	-64.39 pg/mL Standard Deviation 104.463

Adverse Events

Relugolix Plus E2/NETA (Group A)

Serious events: 7 serious events

Other events: 173 other events

Deaths: 0 deaths

Relugolix Plus Delayed E2/NETA (Group B)

Serious events: 19 serious events

Other events: 106 other events

Deaths: 0 deaths

Placebo (Group C)

Serious events: 18 serious events

Other events: 151 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Relugolix Plus E2/NETA (Group A) n=277 participants at risk Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Relugolix Plus Delayed E2/NETA (Group B) n=247 participants at risk Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily coadministered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.	Placebo (Group C) n=275 participants at risk Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study.
Nervous system disorders Headache	13.7% 38/277 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	7.3% 18/247 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	13.8% 38/275 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.
Infections and infestations Vulvovaginal mycotic infection	10.1% 28/277 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	4.9% 12/247 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	5.5% 15/275 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.
Infections and infestations Nasopharyngitis	8.7% 24/277 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	5.7% 14/247 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	8.0% 22/275 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.
Infections and infestations Vaginal infection	7.9% 22/277 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	7.3% 18/247 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	6.2% 17/275 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.
Infections and infestations Urinary tract infection	6.5% 18/277 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	4.9% 12/247 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	5.1% 14/275 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.
Psychiatric disorders Depressed mood	5.4% 15/277 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	2.8% 7/247 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	5.5% 15/275 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.
Reproductive system and breast disorders Vulvovaginal dryness	5.4% 15/277 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	2.8% 7/247 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	3.3% 9/275 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.
Infections and infestations Corona virus infection	4.7% 13/277 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	7.3% 18/247 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.	7.6% 21/275 • Week 24/Baseline up to Week 104 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.

Additional Information

Clinical Trials at Myovant

Myovant Sciences GmbH

Phone: +1 650 238 0250

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place