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LIBERTY 1: 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: NCT03049735
Recruitment Status : Completed
First Posted : February 10, 2017
Results First Posted : April 19, 2022
Last Update Posted : April 19, 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: Estradiol/norethindrone acetate placebo
Drug: Relugolix placebo
Enrollment 388
Recruitment Details A total of 80 study centers globally were initiated in this study, including centers in the United States, Brazil, Italy, Poland, South Africa, and the United Kingdom.
Pre-assignment Details A total of 388 premenopausal women aged 18 to 50 years with heavy menstrual bleeding (≥ 80 milliliters [mL] per cycle for 2 cycles or ≥ 160 mL during 1 cycle documented by the alkaline hematin method) associated with uterine fibroids were randomized. One placebo participant was randomized and not treated due to a serious adverse event.
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 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 128 132 128
Received at Least 1 Dose of Study Drug 128 132 127
Completed 100 103 105
Not Completed 28 29 23
Reason Not Completed
Discontinued due to AE (not dosed)             0             0             1
Other             5             3             1
Lack of Efficacy             4             0             3
Protocol deviation             1             0             0
Pregnancy             0             0             1
Adverse Event             7             18             5
Withdrawal by Subject             10             3             7
Lost to Follow-up             1             5             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 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 128 132 128 388
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 128 participants 132 participants 128 participants 388 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
128
 100.0%
132
 100.0%
128
 100.0%
388
 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 128 participants 132 participants 128 participants 388 participants
42.5  (4.99) 41.3  (5.39) 42.2  (5.70) 42.0  (5.38)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 128 participants 132 participants 128 participants 388 participants
Female
128
 100.0%
132
 100.0%
128
 100.0%
388
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 128 participants 132 participants 128 participants 388 participants
American Indian or Alaska Native
2
   1.6%
5
   3.8%
1
   0.8%
8
   2.1%
Asian
0
   0.0%
2
   1.5%
2
   1.6%
4
   1.0%
Black or African American
59
  46.1%
67
  50.8%
66
  51.6%
192
  49.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
64
  50.0%
53
  40.2%
56
  43.8%
173
  44.6%
Other Race
2
   1.6%
1
   0.8%
1
   0.8%
4
   1.0%
Multiple Race
1
   0.8%
4
   3.0%
2
   1.6%
7
   1.8%
Race Not reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
92
  71.9%
99
  75.0%
104
  81.3%
295
  76.0%
Hispanic or Latino
34
  26.6%
33
  25.0%
23
  18.0%
90
  23.2%
Ethnicity Not reported
2
   1.6%
0
   0.0%
1
   0.8%
3
   0.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 128 participants 132 participants 128 participants 388 participants
United States 98 101 99 298
Brazil 3 5 3 11
Poland 12 16 22 50
Italy 10 7 3 20
South Africa 4 3 0 7
United Kingdom 1 0 1 2
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 last 35 days of treatment (up to Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intention-to-Treat Population: 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 128 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
73.4
(64.91 to 80.85)
18.9
(12.50 to 26.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Relugolix Plus E2/NETA (Group A), Placebo (Group C)
Comments The primary efficacy analysis was the comparison of the relugolix + E2/NETA group with the placebo group with respect to responder rate.
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 54.54
Confidence Interval (2-Sided) 95%
44.3 to 64.78
Estimation Comments Treatment difference is relugolix + 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:

  1. No feminine product returned due to reported amenorrhea;
  2. No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (eDiary) data indicating infrequent non-cyclic bleeding/spotting;
  3. Feminine product collection with a negligible observed MBL volume coupled with eDiary 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 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 128 127
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
52.34
(43.34 to 61.24)
5.51
(2.24 to 11.03)
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 [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 46.83
Confidence Interval (2-Sided) 95%
37.31 to 56.35
Estimation Comments Treatment difference was relugolix plus E2/NETA minus placebo. 95% confidence interval (CI) for difference is based on the normal approximation.
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. 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 for MBL volume at the specified timepoints.
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 89 95
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-84.3
(-93.5 to -75.0)
-23.2
(-32.2 to -14.1)
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 Treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments Assessed at a 2-sided α = 0.05 significance. Treatment difference is relugolix plus E2/NETA minus placebo.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -61.1
Confidence Interval (2-Sided) 95%
-73.5 to -48.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.32
Estimation Comments [Not Specified]
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 participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data for hemoglobin levels at the specified timepoints.
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 30 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
50.0
(31.30 to 68.70)
21.74
(7.46 to 43.70)
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 = 0.0377
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 28.26
Confidence Interval (2-Sided) 95%
3.68 to 52.84
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 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 participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data for uterine fibroid-associated pain at the specified timepoints.
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 58 69
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
43.10
(30.16 to 56.77)
10.14
(4.18 to 19.79)
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 33.0
Confidence Interval (2-Sided) 95%
18.36 to 47.56
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 participants who were randomized to treatment and who received at least 1 dose of study drug and had analyzable data for primary uterine fibroid volume at the specified timepoints.
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 94 102
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
-12.4
(-23.5 to -1.4)
-0.3
(-10.9 to 10.4)
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 0.0921
Comments Based on analysis of covariance model with treatment, randomization stratification factors, Baseline MBL volume, geographic region (North America, Rest of World), and Baseline values as covariate. Assessed at a 2-sided α = 0.05 significance level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -12.1
Confidence Interval (2-Sided) 95%
-26.3 to 2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.19
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 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 for uterine volume at the specified timepoints.
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 97 102
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-12.9
(-19.0 to -6.9)
2.2
(-3.7 to 8.1)
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 0.0002
Comments Based on analysis of covariance model with treatment, randomization stratification factors, Baseline MBL volume, geographic region (North America, Rest of World), and Baseline values as covariate. Assessed at a 2-sided α = 0.05 significance level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -15.1
Confidence Interval (2-Sided) 95%
-23 to -7.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.98
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 maximum symptom severity.

As per the study objective, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only these two 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 for UFS-QoL BPD scores at the specified timepoints.
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 97 103
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-45.0
(-50.7 to -39.3)
-16.1
(-21.6 to -10.5)
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 <0.0001
Comments Treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments Assessed at a 2-sided α = 0.05 significance level. LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -28.9
Confidence Interval (2-Sided) 95%
-36.3 to -21.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.75
Estimation Comments [Not Specified]
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.

As per the objective of the study, the pre-specified secondary analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below.

Time Frame Baseline, 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 analyzable data for BMD at lumbar spine (L1 to L4) at the specified timepoints.
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 co-administered with estradiol/norethindrone acetate (1.0/0.5 mg) for 12 weeks.
Overall Number of Participants Analyzed 101 103
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.470  (0.2915) -1.995  (0.2848)
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
Hide Description

BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck 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.

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 for BMD at the lumbar spine (L1 to L4), total hip, and femoral neck at the specified timepoints.
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 101 103
Least Squares Mean (Standard Error)
Unit of Measure: percent change
Lumbar Spine (L1 to L4) -0.356  (0.2929) 0.052  (0.2896)
Total Hip 0.023  (0.2461) 0.549  (0.2407)
Femoral Neck -0.262  (0.4466) 0.307  (0.4395)
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 CI based on exact binomial 95% CI (Clopper-Pearson).

As per the objective of the study, this 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.
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 co-administered with estradiol/norethindrone acetate (1.0/0.5 mg) for 12 weeks.
Overall Number of Participants Analyzed 128 129
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.94
(6.11 to 17.67)
36.36
(28.17 to 45.18)
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 Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
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.
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 128 127
Measure Type: Number
Unit of Measure: percentage of participants
14.8 9.4
13.Secondary Outcome
Title Predose Trough Concentrations Of Relugolix And Norethindrone (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 analyzable PK 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 92
Mean (Standard Deviation)
Unit of Measure: ng/mL
Relugolix Number Analyzed 92 participants
2.13  (2.144)
NET Number Analyzed 91 participants
0.33  (0.369)
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 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 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 PK 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 91
Mean (Standard Deviation)
Unit of Measure: pg/mL
48.34  (59.660)
15.Secondary Outcome
Title Change From Baseline At Week 24 In Predose Concentrations Of Estradiol In The Relugolix Plus E2/NETA Group
Hide Description

Blood samples for determination of 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 analyzable PK 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 91
Mean (Standard Deviation)
Unit of Measure: pg/mL
-22.95  (84.005)
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. MBL volume was measured using 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 128 127
Median (95% Confidence Interval)
Unit of Measure: weeks
8.3
(8.1 to 8.7)
25.1
(24.1 to 28.1)
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 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 + 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 128 127
Measure Type: Count of Participants
Unit of Measure: Participants
67
  52.3%
7
   5.5%
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 <0.0001
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 67 7
Median (95% Confidence Interval)
Unit of Measure: weeks
11.3
(5.1 to 18.6)
NA [1] 
(NA to NA)
[1]
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.
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
Overall Number of Participants Analyzed 78 10
Median (95% Confidence Interval)
Unit of Measure: weeks
5.3
(5.0 to 9.1)
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 was 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 + 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 30 23
Measure Type: Count of Participants
Unit of Measure: Participants
15
  50.0%
5
  21.7%
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 0.0377
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 In Hemoglobin For Women With a Hemoglobin ≤ 10.5 g/dL At Baseline
Hide Description

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.

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 and had evaluable 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 30 23
Least Squares Mean (Standard Error)
Unit of Measure: percent change
20.8  (3.05) 10.0  (3.53)
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 0.0117
Comments Treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
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 participants who were randomized to treatment and who received at least 1 dose of study drug and had hemoglobin below lower normal limit of normal 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 72 67
Measure Type: Count of Participants
Unit of Measure: Participants
34
  47.2%
17
  25.4%
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 0.0084
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 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 97 103
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-30.9  (2.61) -10.5  (2.55)
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. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
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). Lower score indicates minimal symptom severity and higher score indicates maximum 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 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 97 103
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
44.4  (3.06) 14.6  (2.99)
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. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
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). Lower score indicates minimal symptom severity and higher score indicates maximum 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 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 97 103
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
45.8  (3.19) 15.1  (3.12)
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. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
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 97 103
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
38.0  (2.80) 12.8  (2.73)
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. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
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 128 127
Measure Type: Count of Participants
Unit of Measure: Participants
78
  60.9%
45
  35.4%
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 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]
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 patients (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 97 103
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-45.0  (2.88) -16.1  (2.81)
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. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
29.Secondary Outcome
Title Number Of Responders With At Least 20 Points Decrease In UFS-QoL Bleeding And Pelvic Discomfort Scale Score
Hide Description

A 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 128 127
Measure Type: Count of Participants
Unit of Measure: Participants
79
  61.7%
35
  27.6%
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]
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 97 103
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.1  (0.14) -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 Treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
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 97 103
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.7  (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 Treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
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 97 103
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.5  (0.14) -0.4  (0.14)
33.Secondary Outcome
Title Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire
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 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 76 81
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.1  (0.14) -0.8  (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 Treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. The multiple visits for each participant were the repeated measures as random effect within each participant and an unstructured covariance.
Method Mixed Models Analysis
Comments LS means and p-value for test of difference is relugolix plus E2/NETA minus placebo.
34.Secondary Outcome
Title Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire
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 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 76 81
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.6  (0.16) -0.5  (0.15)
35.Secondary Outcome
Title Participants Achieving Improvement From Baseline In The 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 76 81
Measure Type: Count of Participants
Unit of Measure: Participants
1 Category improvement (-1)
14
  18.4%
28
  34.6%
2 Category improvement (-2)
29
  38.2%
14
  17.3%
3 Category improvement (-3)
22
  28.9%
1
   1.2%
4 Category improvement (-4)
8
  10.5%
5
   6.2%
36.Secondary Outcome
Title Participants Achieving Improvement From Baseline In The PGA Questionnaire 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 76 81
Measure Type: Count of Participants
Unit of Measure: Participants
1 Category improvement (-1)
21
  27.6%
16
  19.8%
2 Category improvement (-2)
18
  23.7%
9
  11.1%
3 Category improvement (-3)
23
  30.3%
4
   4.9%
4 Category improvement (-4)
2
   2.6%
4
   4.9%
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 98 101
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.0  (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 98 101
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.9  (0.14) -0.8  (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 84 95
Measure Type: Count of Participants
Unit of Measure: Participants
33
  39.3%
11
  11.6%
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 58 69
Measure Type: Count of Participants
Unit of Measure: Participants
42
  72.4%
27
  39.1%
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 0.0002
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]
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 91 99
Mean (Standard Deviation)
Unit of Measure: IU/L
-1.90  (20.496) 3.62  (12.524)
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 91 99
Mean (Standard Deviation)
Unit of Measure: IU/L
-6.25  (14.779) 0.10  (11.024)
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 91 99
Mean (Standard Deviation)
Unit of Measure: pg/mL
-22.95  (84.005) 51.72  (145.346)
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 91 99
Mean (Standard Deviation)
Unit of Measure: ng/mL
-0.05  (2.262) 3.00  (4.802)
Time Frame From Baseline to Week 24
Adverse Event Reporting 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) Relugolix Plus Delayed E2/NETA (Group B) Placebo (Group C)
Hide Arm/Group Description Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for 24 weeks. Relugolix 40 mg co-administered with placebo for E2/NETA for 12 weeks followed by relugolix co-administered with estradiol/norethindrone acetate (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   0/128 (0.00%)      0/132 (0.00%)      0/127 (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   7/128 (5.47%)      3/132 (2.27%)      2/127 (1.57%)    
Endocrine disorders       
Hypothyroidism  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
Eye disorders       
Vitreous detachment  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
Gastrointestinal disorders       
Haematemesis  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
Infections and infestations       
Appendicitis  1  0/128 (0.00%)  0 1/132 (0.76%)  1 0/127 (0.00%)  0
Pneumonia  1  0/128 (0.00%)  0 0/132 (0.00%)  0 1/127 (0.79%)  1
Injury, poisoning and procedural complications       
Avulsion fracture  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
Ankle fracture  1  1/128 (0.78%)  1 1/132 (0.76%)  1 0/127 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Rhabdomyolysis  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Uterine myoma expulsion  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
uterine leiomyoma  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
Psychiatric disorders       
Panic attack  1  0/128 (0.00%)  0 1/132 (0.76%)  1 0/127 (0.00%)  0
Acute psychosis  1  0/128 (0.00%)  0 0/132 (0.00%)  0 1/127 (0.79%)  1
Reproductive system and breast disorders       
Menorrhagia  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
Pelvic pain  1  1/128 (0.78%)  1 0/132 (0.00%)  0 0/127 (0.00%)  0
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   32/128 (25.00%)      62/132 (46.97%)      33/127 (25.98%)    
Infections and infestations       
Upper respiratory tract infection  1  1/128 (0.78%)  1 7/132 (5.30%)  7 3/127 (2.36%)  4
Musculoskeletal and connective tissue disorders       
Arthralgia  1  4/128 (3.13%)  6 7/132 (5.30%)  8 4/127 (3.15%)  5
Nervous system disorders       
Headache  1  14/128 (10.94%)  15 14/132 (10.61%)  18 19/127 (14.96%)  20
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/128 (0.78%)  1 0/132 (0.00%)  0 7/127 (5.51%)  7
Vascular disorders       
Hot flush  1  14/128 (10.94%)  14 47/132 (35.61%)  48 10/127 (7.87%)  10
Hypertension  1  7/128 (5.47%)  8 3/132 (2.27%)  5 0/127 (0.00%)  0
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: NCT03049735    
Other Study ID Numbers: MVT-601-3001
2016-003727-27 ( EudraCT Number )
First Submitted: February 8, 2017
First Posted: February 10, 2017
Results First Submitted: January 3, 2022
Results First Posted: April 19, 2022
Last Update Posted: April 19, 2022