A Phase 3 interventional study of Relugolix and Estradiol/norethindrone acetate in Heavy Menstrual Bleeding and Uterine Fibroid, sponsored by Myovant Sciences GmbH. Completed at 127 sites in 8 countries. Open to female participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2022-04-20.
Sponsored by Myovant Sciences GmbH (part of Sumitomo Pharma Co., Ltd.) · Phase 3, Interventional, and Treatment
The purpose of this study is to determine the benefit of relugolix 40 milligrams (mg) once a day co-administered with estradiol (E2) 1 mg and norethindrone acetate (NETA) 0.5 mg compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids.
This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy and safety study to evaluate 24 weeks of oral daily relugolix 40 mg co-administered with low-dose E2 and NETA (Group A) and 12 weeks of daily oral relugolix 40 mg alone followed by 12 weeks of daily oral relugolix 40 mg co-administered with low-dose E2 and NETA (Group B) compared with 24 weeks of placebo (Group C).
All participants completing the Week 24 visit, including participants randomized to placebo, were offered the opportunity to enroll in an open-label extension study in which all eligible participants will receive relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a follow-up visit approximately 30 days after the end of treatment (that is, after the participant's last dose of study medication).
Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and assessments of bone mineral density.
186 studies on the registry are indexed under Menorrhagia; 32 are open to participants now.
This study's enrollment of 382 is above the median of 100 across 137 interventional studies indexed under Menorrhagia.
Browse Menorrhagia studies →Myovant Sciences GmbH is the lead sponsor of 11 studies on the registry; none are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 6 (60%) have results posted.
First submitted before Myovant Sciences GmbH became part of Sumitomo Pharma Co., Ltd..
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Relugolix co-administered with E2/NETA for 24 weeks.
Drug: Relugolix · Drug: Estradiol/norethindrone acetate
Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.
Drug: Relugolix · Drug: Estradiol/norethindrone acetate · Drug: Estradiol/norethindrone acetate placebo
Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.
Drug: Relugolix placebo · Drug: Estradiol/norethindrone acetate placebo
Relugolix (40 mg) tablet administered orally once daily.
Also known as: TAK-385, MVT-601
Drug pages: Estradiol · Norethindrone Acetate
E2 (1.0 mg)/NETA (0.5 mg) co-formulated capsule administered orally once daily.
Also known as: E2/NETA, low-dose hormonal add-back
Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.
E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor.
Also known as: E2/NETA placebo
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
A responder was a participant who had MBL volume of \< 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 24). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 24/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented. As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: From Baseline up to the last 35 days of treatment (up to Week 24)
Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment
Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits: * No feminine product returned due to reported amenorrhea; * No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (e-Diary) data indicating infrequent non-cyclic bleeding/spotting; * Feminine product collection with a negligible observed MBL volume coupled with e-Diary data indicating infrequent non-cyclic bleeding/spotting. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: From Baseline up to last 35 days of treatment (up to Week 24)
Percent Change From Baseline At Week 24 In MBL Volume
MBL volume was measured using the alkaline hematin method. Least square (LS) means for test of difference is Relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: Baseline, Week 24
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
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
Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment
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
Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume
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
Percent Change From Baseline At Week 24 In Uterine Volume
The volume of the uterus was measured by transvaginal or transabdominal ultrasound. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: From Baseline up to Week 24
Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)
The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Bleeding and Pelvic Discomfort (BPD) Scale has been derived from the UFS-QoL Symptoms Scale. The scale consists of the following 3 symptoms proximal to uterine fibroids: Heavy bleeding during your menstrual period (Question \[Q\] 1), passing blood clots during your menstrual period (Q2), and feeling tightness or pressure in your pelvic area (Q5), raw scores were transformed to a normalized score: Transformed Score = \[(Actual raw score - lowest possible raw score)/(Possible raw score range)\]\*100 Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates symptom severity. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms
Time frame: Baseline Week 24
Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 to L4) As Assessed By DXA
Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (L1, L2, L3, and L4) at Baseline and at Week 12. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: From Baseline up to Week 12
Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck As Assessed By DXA
BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck (same leg across participants) at Baseline and at Week 24. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects. For Relugolix plus E2/NETA Lumbar Spine (L1 to L4), number (n)=95. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only rel
Time frame: Baseline through Week 24
Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12
An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term. Reported confidence interval (CI) based on exact binomial 95% CI (Clopper-Pearson). As per the objective of the study, the secondary analysis compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below.
Time frame: Baseline through Week 12
Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24
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
Predose Trough Concentrations Of Relugolix And NET In The Relugolix Plus E2/NETA Group At Week 24
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
Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24
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
Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group
Blood samples for determination of E2 serum concentrations were collected predose at Week 24. Relugolix and NET plasma concentrations were determined using validated bioanalytical methodology. Concentrations below the quantification limit (BQL) were set to 0 for analysis of summary statistics. As per the objective of the study, only relugolix plus E2/NETA concentration is presented.
Time frame: Baseline, Week 24
Time To MBL Response
Defined as the time to achieve an MBL volume of \< 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: From Baseline through Week 24
Sustained Amenorrhea Rate (No Or Negligible Bleeding)
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
Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)
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
Time To Achieving Amenorrhea (No Or Negligible Bleeding)
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
Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL 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.
Time frame: From Baseline through Week 24
Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL 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.
Time frame: Baseline, Week 24
Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal
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
Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score
Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of time, most of the time and all of the time.) Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score
Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Higher scores are indicative of better health-related quality of life (high score = good). As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: Baseline, Week 24
Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score
Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time and all of the time). Higher scores are indicative of better health-related quality of life (high score = good). LS means and p-value for test of difference was relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: Baseline, Week 24
Change From Baseline In UFS-QoL Score by Health-Related Quality of Life Total Score
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
Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale 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: From Baseline through Week 24
Change From Baseline in UFS-QoL Bleeding and Pelvic Discomfort Scale Score
The Bleeding and Pelvic Discomfort Scale consists of 3 items proximal to uterine fibroids that are experienced by most participants (heavy bleeding during the menstrual period \[Question 1\], passing blood clots during the menstrual period \[Question 2\], and feeling tightness or pressure in the pelvic area \[Question 5\]).Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
Time frame: Baseline, Week 24
Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score
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
Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11
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
Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20
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
Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29
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
Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire
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
Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire
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
Participants Achieving Improvement From Baseline In PGA Questionnaire For Symptoms From Baseline At Week 24
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
Participants Achieving Improvement From Baseline In PGA For Uterine Fibroid-related Function From Baseline At Week 24
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
Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities
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
Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities
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
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
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)
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
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
Change From Baseline In Luteinizing Serum Concentration 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.
Time frame: Baseline, Week 24
Change From Baseline In Follicle Stimulating Serum Concentration 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.
Time frame: Baseline, Week 24
Change From Baseline In E2 Serum Concentration 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.
Time frame: Baseline, Week 24
Change From Baseline In Progesterone Serum Concentration 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.
Time frame: Baseline, Week 24
The study was conducted at 99 study centers throughout the world, including centers in the United States, Belgium, Brazil, Chile, Czech Republic, Hungary, Poland, and South Africa.
| Milestone | Relugolix Plus Estradiol (E2])/Norethindrone Acetate (NETA) (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) |
|---|---|---|---|
| Started | 126 | 127 | 129 |
| Completed | 102 | 98 | 102 |
| Not completed | 24 | 29 | 27 |
| Withdrew: Did not receive any study drug | 1 | 0 | 0 |
| Withdrew: Protocol violation | 1 | 2 | 1 |
| Withdrew: Lack of efficacy | 2 | 1 | 1 |
| Withdrew: Pregnancy | 0 | 0 | 1 |
| Withdrew: Adverse event | 2 | 15 | 6 |
| Withdrew: Withdrawal by subject | 13 | 6 | 6 |
| Withdrew: Lost to follow-up | 4 | 2 | 7 |
| Withdrew: Other reason not reported | 1 | 3 | 5 |
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.
| Percentage of participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| 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 | 71.2 (62.42 to 78.95) | 14.73 (9.11 to 22.04) |
Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits: * No feminine product returned due to reported amenorrhea; * No feminine product returned due to reports of spotting/negligible bleeding coupled with electronic diary (e-Diary) data indicating infrequent non-cyclic bleeding/spotting; * Feminine product collection with a negligible observed MBL volume coupled with e-Diary data indicating infrequent non-cyclic bleeding/spotting. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
| Percentage of participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment | 50.40 (41.32 to 59.46) | 3.10 (0.85 to 7.75) |
MBL volume was measured using the alkaline hematin method. Least square (LS) means for test of difference is Relugolix plus E2/NETA minus Placebo based on mixed-effect model with treatment, visit, region, Baseline MBL, and treatment by visit interaction included as fixed effects. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
| percent change | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Percent Change From Baseline At Week 24 In MBL Volume | -84.3 (-95.0 to -73.6) | -15.1 (-25.8 to -4.3) |
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.
| Percentage of participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| 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 | 61.29 (42.19 to 78.15) | 5.41 (0.66 to 18.19) |
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.
| percentage of participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment | 47.06 (34.83 to 59.55) | 17.07 (9.66 to 26.98) |
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.
| percent change | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume | -17.4 (-29.1 to -5.7) | -7.4 (-19.1 to 4.2) |
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.
| percent change | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Percent Change From Baseline At Week 24 In Uterine Volume | -13.8 (-20.4 to -7.1) | -1.5 (-8.2 to 5.1) |
The Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Bleeding and Pelvic Discomfort (BPD) Scale has been derived from the UFS-QoL Symptoms Scale. The scale consists of the following 3 symptoms proximal to uterine fibroids: Heavy bleeding during your menstrual period (Question \[Q\] 1), passing blood clots during your menstrual period (Q2), and feeling tightness or pressure in your pelvic area (Q5), raw scores were transformed to a normalized score: Transformed Score = \[(Actual raw score - lowest possible raw score)/(Possible raw score range)\]\*100 Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates symptom severity. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms
| units on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5) | -51.7 (-57.4 to -46.0) | -18.3 (-24.1 to -12.6) |
Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at the lumbar spine (L1, L2, L3, and L4) at Baseline and at Week 12. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
| percent change | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) |
|---|---|---|
| Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 to L4) As Assessed By DXA | -0.819 ± 0.2686 | -1.919 ± 0.2767 |
BMD was assessed by DXA at the lumbar spine (L1, L2, L3, and L4), total hip, and femoral neck (same leg across participants) at Baseline and at Week 24. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS means were based on a mixed-effect model with visit, region, Baseline MBL volume, age at Baseline, body mass index at Baseline, BMD at Baseline, race, and treatment by visit interaction included as fixed effects. For Relugolix plus E2/NETA Lumbar Spine (L1 to L4), number (n)=95. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only rel
| percent change | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Lumbar Spine (L1-L4) | -0.126 ± 0.2971 | 0.315 ± 0.2909 |
| Total Hip | -0.173 ± 0.2221 | -0.044 ± 0.2200 |
| Femoral Neck | -0.684 ± 0.3730 | 0.019 ± 0.3697 |
An adverse event was defined as an unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats, and flushing were combined to describe vasomotor symptoms. Participants with multiple events for a given preferred term were counted only once for each preferred term. Reported confidence interval (CI) based on exact binomial 95% CI (Clopper-Pearson). As per the objective of the study, the secondary analysis compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA at Week 12 and are presented below.
| percentage of participants | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) |
|---|---|---|
| Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12 | 5.56 (2.26 to 11.11) | 35.71 (27.38 to 44.74) |
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.
| percentage of participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24 | 6.3 | 3.9 |
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.
| ng/mL | Relugolix Plus E2/NETA (Group A) |
|---|---|
| Relugolix | 1.96 ± 2.025 |
| NET | 0.28 ± 0.285 |
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.
| pg/mL | Relugolix Plus E2/NETA (Group A) |
|---|---|
| Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24 | 45.34 ± 46.330 |
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.
| pg/mL | Relugolix Plus E2/NETA (Group A) |
|---|---|
| Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group | -22.30 ± 66.552 |
Defined as the time to achieve an MBL volume of \< 80 mL and a ≥ 50% reduction from Baseline MBL volume as measured by the alkaline hematin method. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
| weeks | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Time To MBL Response | 8.4 (8.1 to 9.0) | 27.1 (25.0 to 27.4) |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Sustained Amenorrhea Rate (No Or Negligible Bleeding) | 63 | 4 |
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.
| weeks | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding) | 16.3 (8.1 to NA) | NA (NA to NA) |
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.
| weeks | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Time To Achieving Amenorrhea (No Or Negligible Bleeding) | 8.9 (5.3 to 16.3) | NA (NA to NA) |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24 | 19 | 2 |
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.
| percent change | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline | 24.3 ± 3.02 | 4.3 ± 2.68 |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal | 35 | 18 |
Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of time, most of the time and all of the time.) Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score | -36.1 ± 2.59 | -13.7 ± 2.61 |
Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Higher scores are indicative of better health-related quality of life (high score = good). As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score | 43.6 ± 2.77 | 17.1 ± 2.80 |
Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time and all of the time). Higher scores are indicative of better health-related quality of life (high score = good). LS means and p-value for test of difference was relugolix plus E2/NETA minus placebo based on mixed-effect model with treatment, visit, region, Baseline MBL and treatment by visit interaction included as fixed effects. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
| units on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score | 44.4 ± 2.90 | 16.5 ± 2.94 |
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.
| units on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline In UFS-QoL Score by Health-Related Quality of Life Total Score | 37.8 ± 2.49 | 13.8 ± 2.51 |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score | 78 | 42 |
The Bleeding and Pelvic Discomfort Scale consists of 3 items proximal to uterine fibroids that are experienced by most participants (heavy bleeding during the menstrual period \[Question 1\], passing blood clots during the menstrual period \[Question 2\], and feeling tightness or pressure in the pelvic area \[Question 5\]).Transformed score ranges from 0 to 100 based on Likert scale (None of time, a little of time, some of the time, most of the time and all of the time). Lower score indicates minimal symptom severity and higher score indicates maximum symptom severity. A negative change from baseline indicates improvement. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline in UFS-QoL Bleeding and Pelvic Discomfort Scale Score | -51.7 ± 2.91 | -18.3 ± 2.95 |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score | 79 | 37 |
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.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11 | -2.0 ± 0.14 | -0.7 ± 0.14 |
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.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20 | -1.8 ± 0.13 | -0.6 ± 0.13 |
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.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29 | -1.4 ± 0.14 | -0.7 ± 0.14 |
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.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire | -2.0 ± 0.14 | -0.8 ± 0.14 |
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.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire | -1.7 ± 0.15 | -0.8 ± 0.15 |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| 1 Category improvement (-1) | 7 | 21 |
| 3 Category improvement (-3) | 22 | 8 |
| 2 Category improvement (-2) | 29 | 18 |
| 4 Category improvement (-4) | 10 | 2 |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| 1 Category improvement (-1) | 13 | 19 |
| 2 Category improvement (-2) | 30 | 13 |
| 3 Category improvement (-3) | 18 | 10 |
| 4 Category improvement (-4) | 4 | 2 |
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.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities | -1.8 ± 0.14 | -0.9 ± 0.14 |
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.
| score on a scale | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities | -1.8 ± 0.14 | -1.0 ± 0.14 |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| 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 | 34 | 17 |
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.
| Participants | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| 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 | 48 | 34 |
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.
| IU/L | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline In Luteinizing Serum Concentration At Week 24 | -3.10 ± 4.807 | 3.04 ± 13.162 |
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.
| IU/L | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline In Follicle Stimulating Serum Concentration At Week 24 | -5.47 ± 9.049 | -0.67 ± 7.422 |
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.
| pg/mL | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline In E2 Serum Concentration At Week 24 | -22.30 ± 66.552 | 39.85 ± 99.578 |
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.
| ng/mL | Relugolix Plus E2/NETA (Group A) | Placebo (Group C) |
|---|---|---|
| Change From Baseline In Progesterone Serum Concentration At Week 24 | 0.12 ± 3.963 | 3.48 ± 5.415 |
Collected over From Day 1 to End of Study (24 Weeks). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | 0/126 (0%) | 1/126 (0.8%) | 31/126 (24.6%) |
| Relugolix Plus Delayed E2/NETA (Group B) | 0/126 (0%) | 2/126 (1.6%) | 67/126 (53.2%) |
| Placebo (Group C) | 0/129 (0%) | 4/129 (3.1%) | 42/129 (32.6%) |
| Event | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) |
|---|---|---|---|
| CholecystitisHepatobiliary disorders | 1/126 | 0/126 | 0/129 |
| Cholecystitis acuteHepatobiliary disorders | 0/126 | 1/126 | 0/129 |
| Intervertebral disc degenerationMusculoskeletal and connective tissue disorders | 0/126 | 1/126 | 0/129 |
| Intervertebral disc protrusionMusculoskeletal and connective tissue disorders | 0/126 | 1/126 | 0/129 |
| Radius fractureInjury, poisoning and procedural complications | 0/126 | 0/126 | 1/129 |
| Road traffic accidentInjury, poisoning and procedural complications | 0/126 | 0/126 | 1/129 |
| AnaemiaBlood and lymphatic system disorders | 0/126 | 0/126 | 1/129 |
| SyncopeNervous system disorders | 0/126 | 0/126 | 1/129 |
| Necrotising fasciitisInfections and infestations | 0/126 | 0/126 | 1/129 |
| Event | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) |
|---|---|---|---|
| Hot flushVascular disorders | 7/126 | 44/126 | 5/129 |
| HeadacheNervous system disorders | 11/126 | 28/126 | 15/129 |
| NauseaGastrointestinal disorders | 6/126 | 4/126 | 10/129 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/126 | 8/126 | 4/129 |
| HypertensionVascular disorders | 5/126 | 7/126 | 4/129 |
| FatigueGeneral disorders | 1/126 | 7/126 | 2/129 |
| AnaemiaBlood and lymphatic system disorders | 2/126 | 2/126 | 7/129 |
| Upper respiratory tract infectionInfections and infestations | 6/126 | 3/126 | 7/129 |
All participants who were enrolled and randomized in the study.
| Age, Categorical(Participants) | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 126 | 127 | 129 | 382 |
| >=65 years | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) | Total |
|---|---|---|---|---|
| Mean | 42.4 ± 5.37 | 42.1 ± 5.25 | 41.8 ± 5.26 | 42.1 ± 5.29 |
| Sex: Female, Male(Participants) | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) | Total |
|---|---|---|---|---|
| Female | 126 | 127 | 129 | 382 |
| Male | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 18 | 34 | 32 | 84 |
| Not Hispanic or Latino | 106 | 91 | 96 | 293 |
| Unknown or Not Reported | 2 | 2 | 1 | 5 |
| Race (NIH/OMB)(Participants) | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 2 | 1 | 3 |
| Asian | 0 | 3 | 1 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 63 | 66 | 74 | 203 |
| White | 58 | 50 | 49 | 157 |
| More than one race | 1 | 1 | 0 | 2 |
| Unknown or Not Reported | 4 | 5 | 4 | 13 |
| Region of Enrollment(participants) | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) | Total |
|---|---|---|---|---|
| Hungary | 7 | 7 | 8 | 22 |
| Belgium | 0 | 3 | 1 | 4 |
| United States | 94 | 94 | 96 | 284 |
| Czechia | 4 | 2 | 3 | 9 |
| Poland | 7 | 6 | 4 | 17 |
| Brazil | 1 | 3 | 1 | 5 |
| South Africa | 7 | 3 | 7 | 17 |
| Chile | 6 | 9 | 9 | 24 |
| Mean MBL Volume(mL) | Relugolix Plus E2/NETA (Group A) | Relugolix Plus Delayed E2/NETA (Group B) | Placebo (Group C) | Total |
|---|---|---|---|---|
| Mean | 247.62 ± 185.553 | 227.41 ± 34.350 | 211.75 ± 129.903 | 228.45 ± 152.205 |
Showing the first 100 of 127 sites across 8 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
Ran from Jun 2017 to primary completion in Jul 2019, 24 months.
Results were first posted in Apr 2022, 2 years 9 months after primary completion. A results delay was requested in May 2020.
Of 18 phase 3 interventional studies under Menorrhagia, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 24 and three quarters within 35. This study's 24 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Relugolix · Estradiol · Norethindrone Acetate