Trial Outcomes & Findings for LIBERTY EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids (NCT NCT03412890)

Last Updated: 2024-05-09

Results Overview

A responder was a participant who had MBL volume of \< 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 52). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 52/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

477 participants

Primary outcome timeframe

Week 52/End of Treatment

Results posted on

2024-05-09

Participant Flow

All participants who completed their participation in one of the pivotal studies (MVT-601-3001 or MVT-601-3002) were eligible to enroll in this study.

The study results were presented by treatment group in the pivotal study but all the participants received relugolix plus Estradiol (E2)/Norethindrone Acetate (NETA) in open-label extension study.

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Overall Study STARTED	163	150	164
Overall Study Received at Least 1 Dose of Study Drug	163	149	164
Overall Study COMPLETED	133	108	122
Overall Study NOT COMPLETED	30	42	42

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Overall Study Adverse Event	5	5	9
Overall Study Protocol deviation	2	1	2
Overall Study Lost to Follow-up	7	10	10
Overall Study Withdrawal by Subject	9	12	11
Overall Study Lack of Efficacy	2	7	5
Overall Study Other	5	6	5
Overall Study Participants who did not receive any study drug	0	1	0

Baseline Characteristics

LIBERTY EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Baseline characteristics by cohort

Baseline characteristics by cohort
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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=149 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=164 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Total n=476 Participants Total of all reporting groups
Age, Continuous	42.6 years STANDARD_DEVIATION 5.08 • n=5 Participants	42.1 years STANDARD_DEVIATION 5.58 • n=7 Participants	41.9 years STANDARD_DEVIATION 5.43 • n=5 Participants	42.2 years STANDARD_DEVIATION 5.36 • n=4 Participants
Sex: Female, Male Female	163 Participants n=5 Participants	149 Participants n=7 Participants	164 Participants n=5 Participants	476 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	38 Participants n=5 Participants	34 Participants n=7 Participants	36 Participants n=5 Participants	108 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	122 Participants n=5 Participants	113 Participants n=7 Participants	126 Participants n=5 Participants	361 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	69 Participants n=5 Participants	81 Participants n=7 Participants	88 Participants n=5 Participants	238 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	85 Participants n=5 Participants	51 Participants n=7 Participants	71 Participants n=5 Participants	207 Participants n=4 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment United States	113 participants n=5 Participants	104 participants n=7 Participants	117 participants n=5 Participants	335 participants n=4 Participants
Region of Enrollment Belgium	0 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants
Region of Enrollment Brazil	4 participants n=5 Participants	6 participants n=7 Participants	2 participants n=5 Participants	12 participants n=4 Participants
Region of Enrollment Chile	5 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants	19 participants n=4 Participants
Region of Enrollment Czechia	4 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Hungary	6 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants	17 participants n=4 Participants
Region of Enrollment Italy	7 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	15 participants n=4 Participants
Region of Enrollment Poland	14 participants n=5 Participants	14 participants n=7 Participants	19 participants n=5 Participants	47 participants n=4 Participants
Region of Enrollment South Africa	10 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	20 participants n=4 Participants
Mean Menstrual Blood Loss (MBL) volume	248.71 mL STANDARD_DEVIATION 196.694 • n=5 Participants	238.78 mL STANDARD_DEVIATION 155.332 • n=7 Participants	216.01 mL STANDARD_DEVIATION 123.786 • n=5 Participants	234.33 mL STANDARD_DEVIATION 161.753 • n=4 Participants
Body Mass Index	31.384 kg/m^2 STANDARD_DEVIATION 7.0470 • n=5 Participants	30.997 kg/m^2 STANDARD_DEVIATION 6.4000 • n=7 Participants	32.577 kg/m^2 STANDARD_DEVIATION 7.4556 • n=5 Participants	31.675 kg/m^2 STANDARD_DEVIATION 7.0162 • n=4 Participants
Bone Mineral Density (BMD) Lumbar Spine (L1-L4)	1.186 g/cm^2 STANDARD_DEVIATION 0.1599 • n=5 Participants	1.225 g/cm^2 STANDARD_DEVIATION 0.1730 • n=7 Participants	1.239 g/cm^2 STANDARD_DEVIATION 0.1573 • n=5 Participants	1.217 g/cm^2 STANDARD_DEVIATION 0.1645 • n=4 Participants
Bone Mineral Density (BMD) Total Hip	1.044 g/cm^2 STANDARD_DEVIATION 0.1382 • n=5 Participants	1.062 g/cm^2 STANDARD_DEVIATION 0.1463 • n=7 Participants	1.069 g/cm^2 STANDARD_DEVIATION 0.1401 • n=5 Participants	1.058 g/cm^2 STANDARD_DEVIATION 0.1415 • n=4 Participants
Bone Mineral Density (BMD) Femoral Neck	0.960 g/cm^2 STANDARD_DEVIATION 0.1572 • n=5 Participants	0.994 g/cm^2 STANDARD_DEVIATION 0.1657 • n=7 Participants	0.994 g/cm^2 STANDARD_DEVIATION 0.1648 • n=5 Participants	0.982 g/cm^2 STANDARD_DEVIATION 0.1630 • n=4 Participants

PRIMARY outcome

Timeframe: Week 52/End of Treatment

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=149 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=164 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Percentage Of Participants Who Achieved Or Maintained An MBL Volume Of <80 Milliliters (mL) And At Least A 50% Reduction From Baseline MBL Volume At Week 52/End Of Treatment	86.50 percentage of participants Interval 80.28 to 91.34	79.87 percentage of participants Interval 72.52 to 85.98	75.00 percentage of participants Interval 67.65 to 81.42

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

MBL volume was measured using the alkaline hematin method, which involves chemically measuring the blood content of used feminine products. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. The least squares (LS) mean was derived for each treatment group using a mixed-effects model with repeated measure with visit, region, and Baseline MBL as fixed effects.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=120 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=103 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=113 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In MBL Volume At Week 52	-251.6 mL Standard Error 16.38	-219.1 mL Standard Error 13.91	-204.7 mL Standard Error 13.31

SECONDARY outcome

Timeframe: Week 24 up to last 35 days of treatment (up to Week 52)

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits: * No feminine product returned due to reported amenorrhea; * No feminine product returned due to reports of spotting/negligible bleeding coupled with other data (participant's paper diary) indicating infrequent non-cyclic bleeding/spotting; and * Feminine product collection with a negligible observed MBL volume coupled with data (participant's paper diary) indicating infrequent non-cyclic bleeding/spotting.

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=149 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=164 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Percentage Of Participants Who Achieved Or Maintained Amenorrhea Over The Last 35 Days Of Treatment	70.55 percentage of participants Interval 62.92 to 77.42	68.46 percentage of participants Interval 60.35 to 75.82	57.93 percentage of participants Interval 49.98 to 65.58

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population with a hemoglobin level ≤10.5 g/dL at pivotal study baseline: all participants who enrolled and received any amount of open-label study drug in the open-label extension study and who had a hemoglobin level ≤10.5 g/dL at pivotal study baseline.

Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin ≤10.5 g/dL at pivotal study Baseline and reported at Week 52.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=39 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=38 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=38 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Percentage Of Participants With A Hemoglobin Level ≤10.5 Gram/Deciliter (g/dL) At Pivotal Study Baseline Who Achieved An Increase Of >2 g/dL From Pivotal Study Baseline At Week 52	58.97 percentage of participants Interval 42.1 to 74.43	78.95 percentage of participants Interval 62.68 to 90.45	42.11 percentage of participants Interval 26.31 to 59.18

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population with a hemoglobin level below lower limit of normal at pivotal study baseline: all participants who enrolled and received any amount of open-label study drug in the open-label extension study and who had a hemoglobin level below lower limit of normal at pivotal study baseline.

Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin concentration below the lower limit of normal (11.6 g/dL) at pivotal study Baseline and reported at Week 52.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=89 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=96 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=98 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Number Of Participants With Hemoglobin Increase Of ≥1 g/dL From Pivotal Study Baseline At Week 52 Among Those With A Hemoglobin Concentration Below Lower Limit Of Normal At Pivotal Baseline	56 participants	60 participants	45 participants

SECONDARY outcome

Timeframe: Week 52

Blood samples were collected from participants for hemoglobin measurements. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=39 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=38 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=38 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In Hemoglobin Concentration At Week 52	2.7 g/dL Standard Error 0.24	3.0 g/dL Standard Error 0.23	1.9 g/dL Standard Error 0.22

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time, and all of the time). Lower score indicates less distress and higher score indicates greater distress. A negative change from baseline indicates improvement. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=108 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=120 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In The UFS-QoL Symptom Severity Scale At Week 52	-37.3 score on a scale Standard Error 2.47	-38.2 score on a scale Standard Error 2.77	-35.0 score on a scale Standard Error 2.48

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

Assessed using the UFS-QoL questionnaire. The UFS-QoL subscale scores include items related to uterine fibroid-associated limitations/impairment in activities, revised activities, concern, energy/mood, control, self-consciousness, and sexual function. The scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good). The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=108 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=120 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52 Sexual function	22.7 score on a scale Standard Error 3.40	22.0 score on a scale Standard Error 3.87	24.1 score on a scale Standard Error 3.62
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52 Concern	56.4 score on a scale Standard Error 2.92	56.4 score on a scale Standard Error 3.10	51.2 score on a scale Standard Error 3.10
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52 Activities	47.8 score on a scale Standard Error 2.72	46.9 score on a scale Standard Error 2.82	45.2 score on a scale Standard Error 2.81
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52 Revised activities	49.2 score on a scale Standard Error 2.78	48.0 score on a scale Standard Error 2.97	46.9 score on a scale Standard Error 2.85
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52 Energy/mood	35.6 score on a scale Standard Error 2.67	38.6 score on a scale Standard Error 2.88	36.5 score on a scale Standard Error 2.79
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52 Control	33.0 score on a scale Standard Error 2.69	36.4 score on a scale Standard Error 2.82	32.2 score on a scale Standard Error 2.91
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52 Self-conscious	31.2 score on a scale Standard Error 3.06	35.4 score on a scale Standard Error 3.40	31.0 score on a scale Standard Error 3.14

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

Assessed using the UFS-QoL Questionnaire. The UFS-QoL total score was the sum of the subscales (concern, activities, revised activities, energy/mood, control, self-conscious, and sexual function). The raw scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good). The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=108 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=120 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In The UFS-QoL Score By Health-Related Quality of Life Total Score At Week 52	40.4 score on a scale Standard Error 2.50	41.7 score on a scale Standard Error 2.68	39.0 score on a scale Standard Error 2.63

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

The BPD scale has been derived from the UFS-QoL symptom severity scale. The scale consists of the following 3 symptoms proximal to uterine fibroids that are experienced by most participants: heavy bleeding during the menstrual period (Question 1), passing blood clots during the menstrual period (Question 2), and feeling tightness or pressure in the pelvic area (Question 5). Raw scores were transformed to a normalized score, with a range of possible scores from 0 to 100 (none of time, a little of time, some of the time, most of the time, and all of the time), where higher scores values are indicative of greater distress and lower scores are indicative of minimal distress. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=108 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=120 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In The Uterine Fibroid Symptom Health-Related Quality of Life (UFS-QoL) Bleeding And Pelvic Discomfort (BPD) Scale At Week 52	-51.3 score on a scale Standard Error 2.66	-51.6 score on a scale Standard Error 3.11	-48.6 score on a scale Standard Error 2.76

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

Volume of the uterus was measured by transvaginal or transabdominal ultrasound. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=136 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=110 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=119 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In Uterine Volume At Week 52	-73.31 cm^3 Standard Error 14.471	-91.67 cm^3 Standard Error 20.143	-37.62 cm^3 Standard Error 14.541

SECONDARY outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

Volume of the primary uterine fibroid was measured by transvaginal or transabdominal ultrasound. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=131 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=103 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=117 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In Uterine Fibroid Volume At Week 52	-31.84 cm^3 Standard Error 5.353	-28.18 cm^3 Standard Error 5.523	-17.07 cm^3 Standard Error 5.726

SECONDARY outcome

Timeframe: Week 52

Population: Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study. The overall number of participants analyzed is then umber of patients at baseline. The number analyzed at each location is the number of patients included in summary statistics for that location and timepoint.

Assessed by dual-energy X-ray absorptiometry (DXA) scan at the lumbar spine (L1-L4), total hip, and femoral neck at pivotal study Baseline and at Week 52. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.

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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=149 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=164 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Percent Change From Pivotal Study Baseline In Bone Mineral Density (BMD) At The Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 Lumbar Spine (L1-L4)	-0.804 percentage change Standard Error 0.2803	-2.045 percentage change Standard Error 0.2679	-0.775 percentage change Standard Error 0.2781
Percent Change From Pivotal Study Baseline In Bone Mineral Density (BMD) At The Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 Total Hip	-0.153 percentage change Standard Error 0.2337	-0.842 percentage change Standard Error 0.2308	-0.065 percentage change Standard Error 0.2086
Percent Change From Pivotal Study Baseline In Bone Mineral Density (BMD) At The Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 Femoral Neck	-0.575 percentage change Standard Error 0.3208	-0.513 percentage change Standard Error 0.4503	0.004 percentage change Standard Error 0.3886

SECONDARY outcome

Timeframe: Week 52

Population: Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.

Blood samples were collected from participants at predose for E2 measurements. These were analyzed at a central laboratory.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=135 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=114 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=125 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In Predose Serum E2 Concentrations At Week 52	-21.83 pg/mL Standard Deviation 91.525	-33.77 pg/mL Standard Deviation 106.407	-29.99 pg/mL Standard Deviation 81.465

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 52

Population: Extension Study Population: all participants who enrolled and received any amount of open-label study drug in the open-label extension study.

The EQ-5D-5L scale is a standardized instrument for use as a measure of health outcomes. Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were each assessed on 5-point categorical scales of no problems to unable to complete specified activity, or no pain/discomfort to extreme pain/discomfort, or not anxious/depressed to extremely anxious/depressed. The change from baseline is summarized by amount of improvement (1-4 categories), amount of deterioration (1-4 categories), or no change.

Outcome measures

Outcome measures
Measure	Relugolix Plus E2/NETA (Group A) n=127 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=108 Participants Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=117 Participants Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - 3 Category improvement	8 Participants	6 Participants	6 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - 4 Category improvement	0 Participants	1 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - 4 Category deterioration	0 Participants	0 Participants	1 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - 3 Category deterioration	0 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - 2 Category deterioration	4 Participants	3 Participants	5 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - 4 Category deterioration	0 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - 3 Category deterioration	0 Participants	1 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - 2 Category deterioration	2 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - 1 Category deterioration	3 Participants	5 Participants	4 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - No change	102 Participants	89 Participants	99 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - 1 Category improvement	15 Participants	9 Participants	10 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - 2 Category improvement	5 Participants	3 Participants	4 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - 3 Category improvement	0 Participants	1 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Mobility - 4 Category improvement	0 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self-care - 4 Category deterioration	0 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self-care - 3 Category deterioration	0 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self-care - 2 Category deterioration	0 Participants	1 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self-care - 1 Category deterioration	1 Participants	1 Participants	2 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self-care - No change	122 Participants	105 Participants	108 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self care - 1 Category improvement	3 Participants	0 Participants	5 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self care - 2 Category improvement	1 Participants	1 Participants	1 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self care - 3 Category improvement	0 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Self care - 4 Category improvement	0 Participants	0 Participants	1 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - 4 Category deterioration	0 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - 3 Category deterioration	0 Participants	1 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - 2 Category deterioration	3 Participants	0 Participants	2 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - 1 Category deterioration	4 Participants	2 Participants	4 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - No change	91 Participants	71 Participants	73 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - 1 Category improvement	15 Participants	22 Participants	22 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - 2 Category improvement	10 Participants	10 Participants	12 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - 3 Category improvement	3 Participants	2 Participants	3 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Usual activities - 4 Category improvement	1 Participants	0 Participants	1 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - 4 Category deterioration	0 Participants	0 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - 3 Category deterioration	0 Participants	1 Participants	2 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - 2 Category deterioration	3 Participants	2 Participants	0 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - 1 Category deterioration	17 Participants	8 Participants	10 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - No change	46 Participants	45 Participants	45 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - 1 Category improvement	37 Participants	31 Participants	37 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Pain/discomfort - 2 Category improvement	16 Participants	14 Participants	17 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - 1 Category deterioration	11 Participants	20 Participants	12 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - No change	79 Participants	53 Participants	69 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - 1 Category improvement	24 Participants	25 Participants	17 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - 2 Category improvement	8 Participants	7 Participants	11 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - 3 Category improvement	0 Participants	0 Participants	1 Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52 Anxiety/depression - 4 Category improvement	1 Participants	0 Participants	1 Participants

Adverse Events

Relugolix Plus E2/NETA (Group A)

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Relugolix Plus Delayed E2/NETA (Group B)

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo (Group C)

Serious events: 11 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Relugolix Plus E2/NETA (Group A) n=163 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=149 participants at risk Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=164 participants at risk Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Nervous system disorders Headache	3.7% 6/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	4.7% 7/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	6.7% 11/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Vascular disorders Hot flush	2.5% 4/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	7.9% 13/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Infections and infestations Nasopharyngitis	6.1% 10/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	2.0% 3/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	4.9% 8/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Vascular disorders Hypertension	1.2% 2/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	2.0% 3/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	6.1% 10/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.

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

Restriction type: LTE60

Measure	Relugolix Plus E2/NETA (Group A) n=163 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 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Relugolix Plus Delayed E2/NETA (Group B) n=149 participants at risk Relugolix 40 mg monotherapy (once daily) for 12 weeks followed by relugolix 40 mg once daily co-administered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.	Placebo (Group C) n=164 participants at risk Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by 28 weeks of relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) in this study.
Blood and lymphatic system disorders Anaemia	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Cardiac disorders Atrial fibrillation	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Hepatobiliary disorders Cholecystitis	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.67% 1/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Hepatobiliary disorders Cholelithiasis	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.67% 1/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Infections and infestations Appendicitis	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	1.2% 2/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.67% 1/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.67% 1/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.67% 1/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Investigations Blood pressure increased	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.67% 1/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Renal and urinary disorders Nephrolithiasis	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Reproductive system and breast disorders Uterine haemorrhage	0.61% 1/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Reproductive system and breast disorders Menorrhagia	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	1.2% 2/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Reproductive system and breast disorders Metrorrhagia	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.
Reproductive system and breast disorders Ovarian cyst ruptured	0.00% 0/163 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.00% 0/149 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.	0.61% 1/164 • Week 24 up to Week 52 Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.