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LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03103087
Recruitment Status : Completed
First Posted : April 6, 2017
Results First Posted : April 20, 2022
Last Update Posted : April 20, 2022
Sponsor:
Information provided by (Responsible Party):
Myovant Sciences GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Heavy Menstrual Bleeding
Uterine Fibroid
Interventions Drug: Relugolix
Drug: Estradiol/norethindrone acetate
Drug: Relugolix placebo
Drug: Estradiol/norethindrone acetate placebo
Enrollment 382
Recruitment Details The study was conducted at 99 study centers throughout the world, including centers in the United States, Belgium, Brazil, Chile, Czech Republic, Hungary, Poland, and South Africa.
Pre-assignment Details A total of 382 premenopausal women aged 18 to 50 years old (inclusive) with heavy menstrual bleeding (≥ 160 milliliters [mL] during 1 cycle or ≥ 80 mL per cycle for 2 menstrual cycles as measured by the alkaline hematin method) associated with uterine fibroids were randomized. One participant was randomized in error before eligibility confirmed.
Arm/Group Title Relugolix Plus Estradiol (E2])/Norethindrone Acetate (NETA) (Group A) Relugolix Plus Delayed E2/NETA (Group B) Placebo (Group C)
Hide Arm/Group Description Relugolix 40 milligrams (mg) co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks. Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks followed by relugolix 40 mg co-administered with E2/NETA (1.0/0.5 mg) for 12 weeks. Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Period Title: Overall Study
Started 126 127 129
Completed 102 98 102
Not Completed 24 29 27
Reason Not Completed
Did not receive any study drug             1             0             0
Protocol Violation             1             2             1
Lack of Efficacy             2             1             1
Pregnancy             0             0             1
Adverse Event             2             15             6
Withdrawal by Subject             13             6             6
Lost to Follow-up             4             2             7
Other reason not reported             1             3             5
Arm/Group Title Relugolix Plus E2/NETA (Group A) Relugolix Plus Delayed E2/NETA (Group B) Placebo (Group C) Total
Hide Arm/Group Description Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks. Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks followed by relugolix 40 mg co-administered with E2/NETA (1.0/0.5 mg) for 12 weeks. Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks Total of all reporting groups
Overall Number of Baseline Participants 126 127 129 382
Hide Baseline Analysis Population Description
All participants who were enrolled and randomized in the study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 127 participants 129 participants 382 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
126
 100.0%
127
 100.0%
129
 100.0%
382
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 126 participants 127 participants 129 participants 382 participants
42.4  (5.37) 42.1  (5.25) 41.8  (5.26) 42.1  (5.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 127 participants 129 participants 382 participants
Female
126
 100.0%
127
 100.0%
129
 100.0%
382
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 127 participants 129 participants 382 participants
Hispanic or Latino
18
  14.3%
34
  26.8%
32
  24.8%
84
  22.0%
Not Hispanic or Latino
106
  84.1%
91
  71.7%
96
  74.4%
293
  76.7%
Unknown or Not Reported
2
   1.6%
2
   1.6%
1
   0.8%
5
   1.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 127 participants 129 participants 382 participants
American Indian or Alaska Native
0
   0.0%
2
   1.6%
1
   0.8%
3
   0.8%
Asian
0
   0.0%
3
   2.4%
1
   0.8%
4
   1.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
63
  50.0%
66
  52.0%
74
  57.4%
203
  53.1%
White
58
  46.0%
50
  39.4%
49
  38.0%
157
  41.1%
More than one race
1
   0.8%
1
   0.8%
0
   0.0%
2
   0.5%
Unknown or Not Reported
4
   3.2%
5
   3.9%
4
   3.1%
13
   3.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 126 participants 127 participants 129 participants 382 participants
Hungary 7 7 8 22
Belgium 0 3 1 4
United States 94 94 96 284
Czechia 4 2 3 9
Poland 7 6 4 17
Brazil 1 3 1 5
South Africa 7 3 7 17
Chile 6 9 9 24
Mean MBL Volume  
Mean (Standard Deviation)
Unit of measure:  mL
Number Analyzed 126 participants 127 participants 129 participants 382 participants
247.62  (185.553) 227.41  (34.350) 211.75  (129.903) 228.45  (152.205)
1.Primary Outcome
Title Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA
Hide Description

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 24). 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 24/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.

As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline up to the last 35 days of treatment (up to Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Overall Number of Participants Analyzed 125 129
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
71.2
(62.42 to 78.95)
14.73
(9.11 to 22.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was stratified by baseline MBL volume (< 225 mL or ≥ 225 mL) and geographic region (North America or Rest of World). Assessed at a 2-sided α = 0.05 significance level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 56.47
Confidence Interval (2-Sided) 95%
46.45 to 66.49
Estimation Comments Treatment difference is relugolix plus E2/NETA minus placebo.
2.Secondary Outcome
Title Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment
Hide Description

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 electronic diary (e-Diary) data indicating infrequent non-cyclic bleeding/spotting;
  • Feminine product collection with a negligible observed MBL volume coupled with e-Diary data indicating infrequent non-cyclic bleeding/spotting.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline up to last 35 days of treatment (up to Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Overall Number of Participants Analyzed 125 129
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
50.40
(41.32 to 59.46)
3.10
(0.85 to 7.75)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America or Rest of World). Assessed at a 2-sided α = 0.05 significance level.
Method Cochran-Mantel-Haenszel
Comments Treatment difference was relugolix plus E2/NETA minus placebo. 95% confidence interval (CI) for the difference is based on the normal approximation.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 47.3
Confidence Interval (2-Sided) 95%
38.04 to 56.56
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline At Week 24 In MBL Volume
Hide Description

MBL volume was measured using the alkaline hematin method. Least square (LS) means for test of difference is Relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Overall Number of Participants Analyzed 125 129
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-84.3
(-95.0 to -73.6)
-15.1
(-25.8 to -4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. Assessed at a 2-sided α = 0.05 significance.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -69.2
Confidence Interval (2-Sided) 95%
-84.1 to -54.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.58
Estimation Comments Treatment difference was relugolix plus E2/NETA minus placebo.
4.Secondary Outcome
Title Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24
Hide Description

Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin ≤ 10.5 gram (g)/deciliter (dL) at Baseline and reported at Week 24.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA with placebo arms are presented.

Time Frame From Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug and had analyzable study data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Overall Number of Participants Analyzed 31 37
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
61.29
(42.19 to 78.15)
5.41
(0.66 to 18.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL). Assessed at a 2-sided α = 0.05 significance level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 55.88
Confidence Interval (2-Sided) 95%
37.25 to 74.52
Estimation Comments Treatment difference is relugolix plus E2/NETA minus placebo. 95% CI for difference is based on the normal approximation.
5.Secondary Outcome
Title Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment
Hide Description

Uterine fibroid-associated pain was assessed by a pain numerical rating scale (NRS). The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).

Participants were asked to document, in an e-Diary, the worst pain associated with their uterine fibroids that they experienced during the last 24 hours, every day until the end of study drug administration. Pain evaluable participants, defined as those who had maximum NRS score ≥ 4 at baseline and had at least 28 days (80% of the last 35 days of treatment) of pain scores recorded in the e-Diary, were analyzed.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.
Overall Number of Participants Analyzed 68 82
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
47.06
(34.83 to 59.55)
17.07
(9.66 to 26.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL). Assessed at a 2-sided α = 0.05 significance level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 29.99
Confidence Interval (2-Sided) 95%
15.6 to 44.38
Estimation Comments Treatment difference is relugolix plus E2/NETA minus placebo. 95% CI for difference is based on the normal approximation.
6.Secondary Outcome
Title Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume
Hide Description

The volume of the primary uterine fibroid was measured by transvaginal or transabdominal ultrasound.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug and had analyzable study data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Overall Number of Participants Analyzed 95 98
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-17.4
(-29.1 to -5.7)
-7.4
(-19.1 to 4.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2153
Comments LS Means based on analysis of covariance model including treatment, randomization stratification factors, Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World), and Baseline values as covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -10
Confidence Interval (2-Sided) 95%
-25.8 to 5.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.03
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percent Change From Baseline At Week 24 In Uterine Volume
Hide Description

The volume of the uterus was measured by transvaginal or transabdominal ultrasound.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Overall Number of Participants Analyzed 95 100
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-13.8
(-20.4 to -7.1)
-1.5
(-8.2 to 5.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0078
Comments LS Means based on analysis of covariance model including treatment, randomization stratification factors, Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World), and Baseline values as covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -12.2
Confidence Interval (2-Sided) 95%
-21.3 to -3.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.57
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)
Hide Description

The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Bleeding and Pelvic Discomfort (BPD) Scale has been derived from the UFS-QoL Symptoms Scale. The scale consists of the following 3 symptoms proximal to uterine fibroids: Heavy bleeding during your menstrual period (Question [Q] 1), passing blood clots during your menstrual period (Q2), and feeling tightness or pressure in your pelvic area (Q5), raw scores were transformed to a normalized score: Transformed Score = [(Actual raw score - lowest possible raw score)/(Possible raw score range)]*100 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 minimal symptom severity and higher score indicates symptom severity.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms

Time Frame Baseline Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Overall Number of Participants Analyzed 96 95
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-51.7
(-57.4 to -46.0)
-18.3
(-24.1 to -12.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Assessed at a 2-sided α = 0.05 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -33.4
Confidence Interval (2-Sided) 95%
-41.2 to -25.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.98
Estimation Comments Relugolix plus E2/NETA minus placebo. Treatment, visit, region, Baseline MBL and treatment by visit interaction as fixed effects.
9.Secondary Outcome
Title Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 to L4) As Assessed By DXA
Hide Description

Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (L1, L2, L3, and L4) at Baseline and at Week 12. 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 means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Relugolix Plus Delayed E2/NETA (Group B)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks followed by relugolix 40 mg co-administered with E2/NETA (1.0/0.5 mg) for 12 weeks.
Overall Number of Participants Analyzed 103 95
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.819  (0.2686) -1.919  (0.2767)
10.Secondary Outcome
Title Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck As Assessed By DXA
Hide Description

BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck (same leg across participants) at Baseline and at Week 24. 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 means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects. For Relugolix plus E2/NETA Lumbar Spine (L1 to L4), number (n)=95.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only rel

Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 98 95
Least Squares Mean (Standard Error)
Unit of Measure: percent change
Lumbar Spine (L1-L4) -0.126  (0.2971) 0.315  (0.2909)
Total Hip -0.173  (0.2221) -0.044  (0.2200)
Femoral Neck -0.684  (0.3730) 0.019  (0.3697)
11.Secondary Outcome
Title Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12
Hide Description An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term. Reported confidence interval (CI) based on exact binomial 95% CI (Clopper-Pearson). As per the objective of the study, the secondary analysis compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below.
Time Frame Baseline through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Relugolix Plus Delayed E2/NETA (Group B)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks followed by relugolix 40 mg co-administered with E2/NETA (1.0/0.5 mg) for 12 weeks.
Overall Number of Participants Analyzed 126 126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.56
(2.26 to 11.11)
35.71
(27.38 to 44.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Relugolix Plus Delayed E2/NETA (Group B)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
0.07 to 0.33
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24
Hide Description

An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term.

Reported percentages based on the total number of participants in each treatment group.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 126 129
Measure Type: Number
Unit of Measure: percentage of participants
6.3 3.9
13.Secondary Outcome
Title Predose Trough Concentrations Of Relugolix And NET In The Relugolix Plus E2/NETA Group At Week 24
Hide Description

Blood samples for determination of relugolix and NET plasma concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.

Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: ng/mL
Relugolix 1.96  (2.025)
NET 0.28  (0.285)
14.Secondary Outcome
Title Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24
Hide Description

Blood samples for determination of relugolix and NET plasma concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.

Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Overall Number of Participants Analyzed 88
Mean (Standard Deviation)
Unit of Measure: pg/mL
45.34  (46.330)
15.Secondary Outcome
Title Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group
Hide Description

Blood samples for determination of E2 serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology.

Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: pg/mL
-22.30  (66.552)
16.Secondary Outcome
Title Time To MBL Response
Hide Description

Defined as the time to achieve an MBL volume of < 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 104 34
Median (97.5% Confidence Interval)
Unit of Measure: weeks
8.4
(8.1 to 9.0)
27.1
(25.0 to 27.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value is based on Log-rank test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World) from the proportional hazard regression model comparing relugolix plus E2/NETA with placebo.
Method Log Rank
Comments [Not Specified]
17.Secondary Outcome
Title Sustained Amenorrhea Rate (No Or Negligible Bleeding)
Hide Description

Sustained amenorrhea is defined as participants time to achieve and maintain amenorrhea until the date of last study drug.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 125 129
Measure Type: Count of Participants
Unit of Measure: Participants
63
  50.4%
4
   3.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value for testing difference between relugolix plus E2/NETA and placebo is based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
18.Secondary Outcome
Title Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)
Hide Description

Sustained amenorrhea status as determined based on time to achieve and maintain amenorrhea status.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 63 4
Median (95% Confidence Interval)
Unit of Measure: weeks
16.3 [1] 
(8.1 to NA)
NA [2] 
(NA to NA)
[1]
Not evaluable.
[2]
Sustained amenorrhea was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is based on Log-rank test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World) from the proportional hazard regression model comparing relugolix plus E2/NETA with placebo.
Method Log Rank
Comments [Not Specified]
19.Secondary Outcome
Title Time To Achieving Amenorrhea (No Or Negligible Bleeding)
Hide Description

Time to amenorrhea was defined as the weeks from date of first dose of study drug to the start of amenorrhea.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.
Overall Number of Participants Analyzed 71 11
Median (95% Confidence Interval)
Unit of Measure: weeks
8.9
(5.3 to 16.3)
NA [1] 
(NA to NA)
[1]
Amenorrhea was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value is based on Log-rank test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World) from the proportional hazard regression model comparing relugolix plus E2/NETA with placebo.
Method Log Rank
Comments [Not Specified]
20.Secondary Outcome
Title Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24
Hide Description As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment, received at least 1 dose of study drug, and had hemoglobin ≤ 10.5 g/dL at Baseline and an assessment at Week 24.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 31 37
Measure Type: Count of Participants
Unit of Measure: Participants
19
  61.3%
2
   5.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
21.Secondary Outcome
Title Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline
Hide Description As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug and had analyzable data at the specified timeframe.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 31 37
Least Squares Mean (Standard Error)
Unit of Measure: percent change
24.3  (3.02) 4.3  (2.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects.
Method Mixed Models Analysis
Comments [Not Specified]
22.Secondary Outcome
Title Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal
Hide Description As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug and had analyzable data at the specified timeframe.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 69 75
Measure Type: Count of Participants
Unit of Measure: Participants
35
  50.7%
18
  24.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World). Lower limit of normal is Hgb < 11.6 g/dL.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score
Hide Description

Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of time, most of the time and all of the time.) Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 96 95
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-36.1  (2.59) -13.7  (2.61)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included.
Method Mixed Models Analysis
Comments [Not Specified]
24.Secondary Outcome
Title Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score
Hide Description

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). Higher scores are indicative of better health-related quality of life (high score = good).

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 96 95
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
43.6  (2.77) 17.1  (2.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.
Method Mixed Models Analysis
Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score
Hide Description

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). Higher scores are indicative of better health-related quality of life (high score = good). LS means and p-value for test of difference was relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 96 95
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
44.4  (2.90) 16.5  (2.94)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.
Method Mixed Models Analysis
Comments [Not Specified]
26.Secondary Outcome
Title Change From Baseline In UFS-QoL Score by Health-Related Quality of Life Total Score
Hide Description

The UFS-QoL total score was the sum of 6 subscales (concern, 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).

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 96 95
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
37.8  (2.49) 13.8  (2.51)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.
Method Mixed Models Analysis
Comments [Not Specified]
27.Secondary Outcome
Title Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score
Hide Description As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 125 129
Measure Type: Count of Participants
Unit of Measure: Participants
78
  62.4%
42
  32.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
28.Secondary Outcome
Title Change From Baseline in UFS-QoL Bleeding and Pelvic Discomfort Scale Score
Hide Description

The Bleeding and Pelvic Discomfort Scale consists of 3 items 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]).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 minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had evaluable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 96 95
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-51.7  (2.91) -18.3  (2.95)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included.
Method Mixed Models Analysis
Comments [Not Specified]
29.Secondary Outcome
Title Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score
Hide Description

Responder was defined as meeting a meaningful change threshold, set as a 20-point change from Baseline, in the Bleeding And Pelvic Discomfort Scale at Week 24 on the transformed score.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 125 129
Measure Type: Count of Participants
Unit of Measure: Participants
79
  63.2%
37
  28.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
30.Secondary Outcome
Title Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11
Hide Description

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 minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 96 95
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.0  (0.14) -0.7  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.
Method Mixed Models Analysis
Comments [Not Specified]
31.Secondary Outcome
Title Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20
Hide Description

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 minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 96 95
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.8  (0.13) -0.6  (0.13)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.
Method Mixed Models Analysis
Comments [Not Specified]
32.Secondary Outcome
Title Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29
Hide Description

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 minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 96 95
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.4  (0.14) -0.7  (0.14)
33.Secondary Outcome
Title Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire
Hide Description

PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 80 84
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.0  (0.14) -0.8  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects.
Method Mixed Models Analysis
Comments [Not Specified]
34.Secondary Outcome
Title Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire
Hide Description

PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]).

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 80 84
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.7  (0.15) -0.8  (0.15)
35.Secondary Outcome
Title Participants Achieving Improvement From Baseline In PGA Questionnaire For Symptoms From Baseline At Week 24
Hide Description

The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at baseline to moderate.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 80 84
Measure Type: Count of Participants
Unit of Measure: Participants
1 Category improvement (-1)
7
   8.8%
21
  25.0%
3 Category improvement (-3)
22
  27.5%
8
   9.5%
2 Category improvement (-2)
29
  36.3%
18
  21.4%
4 Category improvement (-4)
10
  12.5%
2
   2.4%
36.Secondary Outcome
Title Participants Achieving Improvement From Baseline In PGA For Uterine Fibroid-related Function From Baseline At Week 24
Hide Description

The PGAs assessed participants' limitation in activities and the severity of symptoms due to uterine fibroids over the previous 4 weeks, as perceived by the participant. The PGA for function and symptoms was evaluated using a 5-point response scale (no limitation at all [1], mild limitation [2], moderate limitation [3], quite a bit of limitation [4], and extreme limitation [5]). Category improvements for symptoms are presented. A 1-category improvement would be severe at Baseline to moderate.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 80 84
Measure Type: Count of Participants
Unit of Measure: Participants
1 Category improvement (-1)
13
  16.3%
19
  22.6%
2 Category improvement (-2)
30
  37.5%
13
  15.5%
3 Category improvement (-3)
18
  22.5%
10
  11.9%
4 Category improvement (-4)
4
   5.0%
2
   2.4%
37.Secondary Outcome
Title Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities
Hide Description

The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 94 95
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.8  (0.14) -0.9  (0.14)
38.Secondary Outcome
Title Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities
Hide Description

The Menorrhagia Impact was evaluated using a 5-point response scale to assess level of improvement from Baseline to Week 24. Response scale: Not at all, 2. Slightly, 3.Moderately, 4. Quite a bit and 5. Extremely.

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 94 95
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.8  (0.14) -1.0  (0.14)
39.Secondary Outcome
Title Number Of Participants Who Achieved A Maximum NRS Score ≤ 1 For Uterine Fibroid-associated Pain Over The Last 35 Days Of Treatment Who Had Maximum Pain Scores ≥ 4 During The 35 Days Prior To Randomization
Hide Description

Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame From Baseline up to the last 35 days of treatment (up to 24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug who had a maximum NRS score ≥ 4 at baseline.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 93 95
Measure Type: Count of Participants
Unit of Measure: Participants
34
  36.6%
17
  17.9%
40.Secondary Outcome
Title Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline
Hide Description

Uterine fibroid-associated pain was assessed by a pain NRS. The pain NRS is a validated, single-item, self-reported measure, which asks respondents to rank their pain on an 11-point scale as follows: 0 (no pain), 1 to 3 (mild pain), 4 to 6 (moderate pain), and 7 to 10 (severe pain).

As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug who had a maximum NRS score ≥ 4 at baseline and had at least 28 days (80% of the last 35 days of treatment) of pain scores recorded in the e-Diary.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 68 82
Measure Type: Count of Participants
Unit of Measure: Participants
48
  70.6%
34
  41.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments P-value was based on Cochran-Mantel-Haenszel test stratified by Baseline MBL volume (< 225 mL, ≥ 225 mL) and geographic region (North America, Rest of World).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
41.Secondary Outcome
Title Change From Baseline In Luteinizing Serum Concentration At Week 24
Hide Description As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 92 93
Mean (Standard Deviation)
Unit of Measure: IU/L
-3.10  (4.807) 3.04  (13.162)
42.Secondary Outcome
Title Change From Baseline In Follicle Stimulating Serum Concentration At Week 24
Hide Description As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 92 93
Mean (Standard Deviation)
Unit of Measure: IU/L
-5.47  (9.049) -0.67  (7.422)
43.Secondary Outcome
Title Change From Baseline In E2 Serum Concentration At Week 24
Hide Description As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 93 90
Mean (Standard Deviation)
Unit of Measure: pg/mL
-22.30  (66.552) 39.85  (99.578)
44.Secondary Outcome
Title Change From Baseline In Progesterone Serum Concentration At Week 24
Hide Description As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Arm/Group Title Relugolix Plus E2/NETA (Group A) Placebo (Group C)
Hide Arm/Group Description:
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
Overall Number of Participants Analyzed 92 93
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.12  (3.963) 3.48  (5.415)
Time Frame From Day 1 to End of Study (24 Weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Relugolix Plus E2/NETA (Group A) Relugolix Plus Delayed E2/NETA (Group B) Placebo (Group C)
Hide Arm/Group Description Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks. Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks followed by relugolix 40 mg co-administered with E2/NETA (1.0/0.5 mg) for 12 weeks. Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks
All-Cause Mortality
Relugolix Plus E2/NETA (Group A) Relugolix Plus Delayed E2/NETA (Group B) Placebo (Group C)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/126 (0.00%)      0/126 (0.00%)      0/129 (0.00%)    
Hide Serious Adverse Events
Relugolix Plus E2/NETA (Group A) Relugolix Plus Delayed E2/NETA (Group B) Placebo (Group C)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/126 (0.79%)      2/126 (1.59%)      4/129 (3.10%)    
Blood and lymphatic system disorders       
Anaemia  1  0/126 (0.00%)  0 0/126 (0.00%)  0 1/129 (0.78%)  1
Hepatobiliary disorders       
Cholecystitis  1  1/126 (0.79%)  1 0/126 (0.00%)  0 0/129 (0.00%)  0
Cholecystitis acute  1  0/126 (0.00%)  0 1/126 (0.79%)  1 0/129 (0.00%)  0
Infections and infestations       
Necrotising fasciitis  1  0/126 (0.00%)  0 0/126 (0.00%)  0 1/129 (0.78%)  1
Injury, poisoning and procedural complications       
Radius fracture  1  0/126 (0.00%)  0 0/126 (0.00%)  0 1/129 (0.78%)  1
Road traffic accident  1  0/126 (0.00%)  0 0/126 (0.00%)  0 1/129 (0.78%)  1
Musculoskeletal and connective tissue disorders       
Intervertebral disc degeneration  1  0/126 (0.00%)  0 1/126 (0.79%)  1 0/129 (0.00%)  0
Intervertebral disc protrusion  1  0/126 (0.00%)  0 1/126 (0.79%)  1 0/129 (0.00%)  0
Nervous system disorders       
Syncope  1  0/126 (0.00%)  0 0/126 (0.00%)  0 1/129 (0.78%)  1
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Relugolix Plus E2/NETA (Group A) Relugolix Plus Delayed E2/NETA (Group B) Placebo (Group C)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/126 (24.60%)      67/126 (53.17%)      42/129 (32.56%)    
Blood and lymphatic system disorders       
Anaemia  1  2/126 (1.59%)  2 2/126 (1.59%)  2 7/129 (5.43%)  7
Gastrointestinal disorders       
Nausea  1  6/126 (4.76%)  6 4/126 (3.17%)  4 10/129 (7.75%)  11
General disorders       
Fatigue  1  1/126 (0.79%)  1 7/126 (5.56%)  7 2/129 (1.55%)  2
Infections and infestations       
Upper respiratory tract infection  1  6/126 (4.76%)  6 3/126 (2.38%)  3 7/129 (5.43%)  7
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/126 (0.79%)  1 8/126 (6.35%)  11 4/129 (3.10%)  6
Nervous system disorders       
Headache  1  11/126 (8.73%)  15 28/126 (22.22%)  34 15/129 (11.63%)  21
Vascular disorders       
Hot flush  1  7/126 (5.56%)  7 44/126 (34.92%)  46 5/129 (3.88%)  5
Hypertension  1  5/126 (3.97%)  5 7/126 (5.56%)  7 4/129 (3.10%)  4
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trials at Myovant
Organization: Myovant Sciences GmbH
Phone: +1 650 238 0250
EMail: clinicaltrials@myovant.com
Layout table for additonal information
Responsible Party: Myovant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03103087    
Other Study ID Numbers: MVT-601-3002
2016-005113-50 ( EudraCT Number )
First Submitted: February 8, 2017
First Posted: April 6, 2017
Results First Submitted: March 23, 2022
Results First Posted: April 20, 2022
Last Update Posted: April 20, 2022