Trial Outcomes & Findings for LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids (NCT NCT03049735)
NCT ID: NCT03049735
Last Updated: 2022-04-19
Results Overview
A responder was a participant who had MBL volume of \< 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 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.
COMPLETED
PHASE3
388 participants
From Baseline up to last 35 days of treatment (up to Week 24)
2022-04-19
Participant Flow
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.
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.
Participant milestones
| Measure |
Relugolix Plus Estradiol (E2)/ Norethindrone Acetate (NETA) (Group A)
Relugolix 40 milligrams (mg) co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Relugolix Plus Delayed E2/NETA (Group B)
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 (Group C)
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
128
|
132
|
128
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
128
|
132
|
127
|
|
Overall Study
COMPLETED
|
100
|
103
|
105
|
|
Overall Study
NOT COMPLETED
|
28
|
29
|
23
|
Reasons for withdrawal
| Measure |
Relugolix Plus Estradiol (E2)/ Norethindrone Acetate (NETA) (Group A)
Relugolix 40 milligrams (mg) co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Relugolix Plus Delayed E2/NETA (Group B)
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 (Group C)
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|---|
|
Overall Study
Discontinued due to AE (not dosed)
|
0
|
0
|
1
|
|
Overall Study
Other
|
5
|
3
|
1
|
|
Overall Study
Lack of Efficacy
|
4
|
0
|
3
|
|
Overall Study
Protocol deviation
|
1
|
0
|
0
|
|
Overall Study
Pregnancy
|
0
|
0
|
1
|
|
Overall Study
Adverse Event
|
7
|
18
|
5
|
|
Overall Study
Withdrawal by Subject
|
10
|
3
|
7
|
|
Overall Study
Lost to Follow-up
|
1
|
5
|
5
|
Baseline Characteristics
LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Baseline characteristics by cohort
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Relugolix Plus Delayed E2/NETA (Group B)
n=132 Participants
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 (Group C)
n=128 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
Total
n=388 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
128 Participants
n=93 Participants
|
132 Participants
n=4 Participants
|
128 Participants
n=27 Participants
|
388 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Continuous
|
42.5 years
STANDARD_DEVIATION 4.99 • n=93 Participants
|
41.3 years
STANDARD_DEVIATION 5.39 • n=4 Participants
|
42.2 years
STANDARD_DEVIATION 5.70 • n=27 Participants
|
42.0 years
STANDARD_DEVIATION 5.38 • n=483 Participants
|
|
Sex: Female, Male
Female
|
128 Participants
n=93 Participants
|
132 Participants
n=4 Participants
|
128 Participants
n=27 Participants
|
388 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
59 Participants
n=93 Participants
|
67 Participants
n=4 Participants
|
66 Participants
n=27 Participants
|
192 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White
|
64 Participants
n=93 Participants
|
53 Participants
n=4 Participants
|
56 Participants
n=27 Participants
|
173 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Other Race
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Multiple Race
|
1 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Race Not reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
92 Participants
n=93 Participants
|
99 Participants
n=4 Participants
|
104 Participants
n=27 Participants
|
295 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
34 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
90 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Ethnicity Not reported
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
98 participants
n=93 Participants
|
101 participants
n=4 Participants
|
99 participants
n=27 Participants
|
298 participants
n=483 Participants
|
|
Region of Enrollment
Brazil
|
3 participants
n=93 Participants
|
5 participants
n=4 Participants
|
3 participants
n=27 Participants
|
11 participants
n=483 Participants
|
|
Region of Enrollment
Poland
|
12 participants
n=93 Participants
|
16 participants
n=4 Participants
|
22 participants
n=27 Participants
|
50 participants
n=483 Participants
|
|
Region of Enrollment
Italy
|
10 participants
n=93 Participants
|
7 participants
n=4 Participants
|
3 participants
n=27 Participants
|
20 participants
n=483 Participants
|
|
Region of Enrollment
South Africa
|
4 participants
n=93 Participants
|
3 participants
n=4 Participants
|
0 participants
n=27 Participants
|
7 participants
n=483 Participants
|
|
Region of Enrollment
United Kingdom
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
2 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: From Baseline up to last 35 days of treatment (up to Week 24)Population: Modified Intention-to-Treat Population: All participants who were randomized to treatment and who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=127 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
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
|
73.4 Percentage of participants
Interval 64.91 to 80.85
|
18.9 Percentage of participants
Interval 12.5 to 26.8
|
SECONDARY outcome
Timeframe: From Baseline up to last 35 days of treatment (up to Week 24)Population: All participants who were randomized to treatment and who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=127 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment
|
52.34 percentage of participants
Interval 43.34 to 61.24
|
5.51 percentage of participants
Interval 2.24 to 11.03
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=89 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=95 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percent Change From Baseline At Week 24 In MBL Volume
|
-84.3 percent change
Interval -93.5 to -75.0
|
-23.2 percent change
Interval -32.2 to -14.1
|
SECONDARY outcome
Timeframe: From Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=30 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=23 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
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
|
50.0 Percentage of participants
Interval 31.3 to 68.7
|
21.74 Percentage of participants
Interval 7.46 to 43.7
|
SECONDARY outcome
Timeframe: From Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=58 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=69 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percentage Of Participants With A Maximum NRS Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment
|
43.10 Percentage of participants
Interval 30.16 to 56.77
|
10.14 Percentage of participants
Interval 4.18 to 19.79
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=94 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=102 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume
|
-12.4 Percent change
Interval -23.5 to -1.4
|
-0.3 Percent change
Interval -10.9 to 10.4
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=102 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percent Change From Baseline At Week 24 In Uterine Volume
|
-12.9 percent change
Interval -19.0 to -6.9
|
2.2 percent change
Interval -3.7 to 8.1
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)
|
-45.0 units on a scale
Interval -50.7 to -39.3
|
-16.1 units on a scale
Interval -21.6 to -10.5
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=101 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 To L4), As Assessed By DXA
|
-0.470 percent change
Standard Error 0.2915
|
-1.995 percent change
Standard Error 0.2848
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=101 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck
Lumbar Spine (L1 to L4)
|
-0.356 percent change
Standard Error 0.2929
|
0.052 percent change
Standard Error 0.2896
|
|
Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck
Total Hip
|
0.023 percent change
Standard Error 0.2461
|
0.549 percent change
Standard Error 0.2407
|
|
Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck
Femoral Neck
|
-0.262 percent change
Standard Error 0.4466
|
0.307 percent change
Standard Error 0.4395
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: All participants who were randomized to treatment and who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=129 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12
|
10.94 percentage of participants
Interval 6.11 to 17.67
|
36.36 percentage of participants
Interval 28.17 to 45.18
|
SECONDARY outcome
Timeframe: Baseline through Week 24Population: All participants who were randomized to treatment and who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=127 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24
|
14.8 percentage of participants
|
9.4 percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=92 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Predose Trough Concentrations Of Relugolix And Norethindrone (NET) In The Relugolix Plus E2/NETA Group At Week 24
Relugolix
|
2.13 ng/mL
Standard Deviation 2.144
|
—
|
|
Predose Trough Concentrations Of Relugolix And Norethindrone (NET) In The Relugolix Plus E2/NETA Group At Week 24
NET
|
0.33 ng/mL
Standard Deviation 0.369
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=91 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24
|
48.34 pg/mL
Standard Deviation 59.660
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=91 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In Predose Concentrations Of Estradiol In The Relugolix Plus E2/NETA Group
|
-22.95 pg/mL
Standard Deviation 84.005
|
—
|
SECONDARY outcome
Timeframe: From Baseline through Week 24Population: All participants who were randomized to treatment and who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=127 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Time To MBL Response
|
8.3 weeks
Interval 8.1 to 8.7
|
25.1 weeks
Interval 24.1 to 28.1
|
SECONDARY outcome
Timeframe: Week 24Population: All participants who were randomized to treatment and who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=127 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Sustained Amenorrhea Rate (No Or Negligible Bleeding)
|
67 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: From Baseline through Week 24Population: All participants who were randomized to treatment and who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=67 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=7 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)
|
11.3 weeks
Interval 5.1 to 18.6
|
NA weeks
Sustained amenorrhea was not reached.
|
SECONDARY outcome
Timeframe: From Baseline through Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=78 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=10 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Time To Achieving Amenorrhea (No Or Negligible Bleeding)
|
5.3 weeks
Interval 5.0 to 9.1
|
NA weeks
Amenorrhea was not reached.
|
SECONDARY outcome
Timeframe: From Baseline through Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=30 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=23 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24
|
15 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=30 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=23 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Percent Change From Baseline In Hemoglobin For Women With a Hemoglobin ≤ 10.5 g/dL At Baseline
|
20.8 percent change
Standard Error 3.05
|
10.0 percent change
Standard Error 3.53
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=72 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=67 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal
|
34 Participants
|
17 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score
|
-30.9 score on a scale
Standard Error 2.61
|
-10.5 score on a scale
Standard Error 2.55
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score
|
44.4 score on a scale
Standard Error 3.06
|
14.6 score on a scale
Standard Error 2.99
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score
|
45.8 units on a scale
Standard Error 3.19
|
15.1 units on a scale
Standard Error 3.12
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline In UFS-QoL Score By Health-Related Quality Of Life Total Score
|
38.0 units on a scale
Standard Error 2.80
|
12.8 units on a scale
Standard Error 2.73
|
SECONDARY outcome
Timeframe: From Baseline through Week 24Population: All participants who were randomized to treatment and who received at least 1 dose of 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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=127 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score
|
78 Participants
|
45 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline In UFS-QoL Bleeding And Pelvic Discomfort Scale Score
|
-45.0 score on a scale
Standard Error 2.88
|
-16.1 score on a scale
Standard Error 2.81
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: All participants who were randomized to treatment and who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=127 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Number Of Responders With At Least 20 Points Decrease In UFS-QoL Bleeding And Pelvic Discomfort Scale Score
|
79 Participants
|
35 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11
|
-2.1 score on a scale
Standard Error 0.14
|
-0.6 score on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20
|
-1.7 score on a scale
Standard Error 0.14
|
-0.7 score on a scale
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=97 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=103 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29
|
-1.5 score on a scale
Standard Error 0.14
|
-0.4 score on a scale
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=76 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=81 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire
|
-2.1 score on a scale
Standard Error 0.14
|
-0.8 score on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=76 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=81 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire
|
-1.6 score on a scale
Standard Error 0.16
|
-0.5 score on a scale
Standard Error 0.15
|
SECONDARY outcome
Timeframe: From Baseline through Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=76 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=81 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Participants Achieving Improvement From Baseline In The PGA Questionnaire For Symptoms From Baseline At Week 24
1 Category improvement (-1)
|
14 Participants
|
28 Participants
|
|
Participants Achieving Improvement From Baseline In The PGA Questionnaire For Symptoms From Baseline At Week 24
2 Category improvement (-2)
|
29 Participants
|
14 Participants
|
|
Participants Achieving Improvement From Baseline In The PGA Questionnaire For Symptoms From Baseline At Week 24
3 Category improvement (-3)
|
22 Participants
|
1 Participants
|
|
Participants Achieving Improvement From Baseline In The PGA Questionnaire For Symptoms From Baseline At Week 24
4 Category improvement (-4)
|
8 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: From Baseline through Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=76 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=81 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Participants Achieving Improvement From Baseline In The PGA Questionnaire For Uterine Fibroid-related Function From Baseline At Week 24
1 Category improvement (-1)
|
21 Participants
|
16 Participants
|
|
Participants Achieving Improvement From Baseline In The PGA Questionnaire For Uterine Fibroid-related Function From Baseline At Week 24
2 Category improvement (-2)
|
18 Participants
|
9 Participants
|
|
Participants Achieving Improvement From Baseline In The PGA Questionnaire For Uterine Fibroid-related Function From Baseline At Week 24
3 Category improvement (-3)
|
23 Participants
|
4 Participants
|
|
Participants Achieving Improvement From Baseline In The PGA Questionnaire For Uterine Fibroid-related Function From Baseline At Week 24
4 Category improvement (-4)
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=98 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=101 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities
|
-2.0 score on a scale
Standard Error 0.14
|
-0.9 score on a scale
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=98 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=101 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities
|
-1.9 score on a scale
Standard Error 0.14
|
-0.8 score on a scale
Standard Error 0.14
|
SECONDARY outcome
Timeframe: From Baseline up to the last 35 days of treatment (up to 24 weeks)Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=84 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=95 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
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
|
33 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=58 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=69 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
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
|
42 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=91 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=99 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline In Luteinizing Serum Concentration At Week 24
|
-1.90 IU/L
Standard Deviation 20.496
|
3.62 IU/L
Standard Deviation 12.524
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=91 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=99 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline In Follicle Stimulating Serum Concentration At Week 24
|
-6.25 IU/L
Standard Deviation 14.779
|
0.10 IU/L
Standard Deviation 11.024
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=91 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=99 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline In E2 Serum Concentration At Week 24
|
-22.95 pg/mL
Standard Deviation 84.005
|
51.72 pg/mL
Standard Deviation 145.346
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Relugolix Plus E2/NETA (Group A)
n=91 Participants
Relugolix 40 mg co-administered with E2 (1.0 mg) and NETA (0.5 mg) for 24 weeks.
|
Placebo (Group C)
n=99 Participants
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|
|
Change From Baseline In Progesterone Serum Concentration At Week 24
|
-0.05 ng/mL
Standard Deviation 2.262
|
3.00 ng/mL
Standard Deviation 4.802
|
Adverse Events
Relugolix Plus E2/NETA (Group A)
Relugolix Plus Delayed E2/NETA (Group B)
Placebo (Group C)
Serious adverse events
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 participants at risk
Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for 24 weeks.
|
Relugolix Plus Delayed E2/NETA (Group B)
n=132 participants at risk
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 (Group C)
n=127 participants at risk
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Avulsion fracture
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.76%
1/132 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine myoma expulsion
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
uterine leiomyoma
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Eye disorders
Vitreous detachment
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/128 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.76%
1/132 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Acute psychosis
|
0.00%
0/128 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.79%
1/127 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Haematemesis
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Endocrine disorders
Hypothyroidism
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/128 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.76%
1/132 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/128 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.79%
1/127 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Relugolix Plus E2/NETA (Group A)
n=128 participants at risk
Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for 24 weeks.
|
Relugolix Plus Delayed E2/NETA (Group B)
n=132 participants at risk
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 (Group C)
n=127 participants at risk
Placebo for relugolix co-administered with placebo for E2/NETA for 24 weeks.
|
|---|---|---|---|
|
Vascular disorders
Hot flush
|
10.9%
14/128 • Number of events 14 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
35.6%
47/132 • Number of events 48 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
7.9%
10/127 • Number of events 10 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Vascular disorders
Hypertension
|
5.5%
7/128 • Number of events 8 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
2.3%
3/132 • Number of events 5 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/127 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
10.9%
14/128 • Number of events 15 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
10.6%
14/132 • Number of events 18 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
15.0%
19/127 • Number of events 20 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.1%
4/128 • Number of events 6 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
5.3%
7/132 • Number of events 8 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
3.1%
4/127 • Number of events 5 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
5.3%
7/132 • Number of events 7 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
2.4%
3/127 • Number of events 4 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.78%
1/128 • Number of events 1 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
0.00%
0/132 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
5.5%
7/127 • Number of events 7 • From Baseline to Week 24
All participants who were randomized to treatment and who received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60