Uterine Fibroids, Uterine Leiomyoma
Conditions
Keywords
Heavy menstrual bleeding, Menorrhagia, Uterine Fibroids, Uterine Leiomyoma
Brief summary
The objectives of this randomized withdrawal study are to evaluate the long-term efficacy and safety of the combination of relugolix, estradiol (E2) and norethindrone acetate (NETA), once daily, for up to 104 weeks in patients with uterine fibroids who have completed a total of 52 weeks of treatment, including a 24-week treatment period in a parent study (study MVT-601-3001 or MVT-601-3002) and a 28-week treatment period in the open-label extension study (MVT-601-3003), and who meet the definition of responder, defined as a patient who demonstrates a menstrual blood loss of \< 80 mL and at least a 50% reduction from parent study baseline menstrual blood loss volume on the alkaline hematin analysis of the feminine products returned at Week 48 in the extension study.
Detailed description
This randomized withdrawal study is an international phase 3 double-blind, placebo-controlled study that will enroll eligible patients with uterine fibroids who have completed the 24-week treatment period in a parent study (MVT-601-3001 or MVT-601-3002) and the 28-week treatment period of the open-label extension study (MVT-601-3003). When including treatment during the parent study and the extension study, patients completing this randomized withdrawal study will have received up to a total of 104 weeks of treatment with relugolix. Approximately 360 women with heavy menstrual bleeding associated with uterine fibroids completing the extension study with a response to treatment will be eligible to participate in this study. A responder is defined as a patient who demonstrates a menstrual blood loss of \< 80 mL and at least a 50% reduction from parent study baseline menstrual blood loss volume on the alkaline hematin analysis of the feminine products returned at Week 48 in the extension study. Screening procedures will be done on the same day as the Week 52 visit for the extension study. This visit will be referred to as the Week 52/Baseline visit. When the Week 52/Baseline procedures in the extension study have been completed, the investigator will assess patient eligibility for participation in this study. The eligibility assessment will be based on data available at the Week 52/Baseline visit. Patients will be asked to provide feminine products for alkaline hematin analysis at each visit until the analysis confirms the return of heavy menstrual bleeding. The patients will then be offered retreatment with open-label relugolix with E2/NETA with the onset of the next menses. They will resume collection of feminine products for alkaline hematin analysis until two consecutive analyses confirm resolution of heavy menstrual bleeding (menstrual blood loss of \< 80 mL). Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, and assessments of bone mineral density.
Interventions
DRUGRelugolix
Relugolix 40 mg tablet administered orally once daily
Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily
DRUGPlacebo for relugolix
Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor
Placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor
Sponsors
Myovant Sciences GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized withdrawal following an open-label extension to a randomized controlled parent study
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 51 Years
Healthy volunteers
No
Inclusion criteria
1. Completed the open-label extension study (MVT-601-3003). 2. Is a responder: Has a menstrual blood loss of \< 80 mL AND at least a 50% reduction from the parent study Baseline based on the results of the alkaline hematin testing performed on the feminine products returned at the Week 48 visit of the extension study. 3. Is not expected to undergo gynecological surgery or ablation procedures for uterine fibroids within the study period
Exclusion criteria
1. Has undergone myomectomy, ultrasound-guided laparoscopic radiofrequency ablation, or any other surgical procedure for fibroids, uterine artery embolization, magnetic resonance guided focused ultrasound for fibroids, or endometrial ablation for abnormal uterine bleeding at any time during the Parent study or extension study. 2. Has a weight that exceeds the weight limit of the dual-energy x-ray absorptiometry (DXA) scanner 3. Has developed any contraindication to treatment with estradiol or norethindrone acetate 4. Is currently pregnant or lactating, or intends to become pregnant during the study period 5. Met a withdrawal criterion in the open-label extension (OLE) study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period | Week 52/Baseline up to Week 76 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. The sustained responder rate was calculated as the Kaplan-Meier estimate of the cumulative probability of MBL volume \< 80 mL through Week 76 using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period | Week 52/Baseline up to Week 104 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. The sustained responder rate was calculated as the Kaplan-Meier estimate of the cumulative probability of MBL volume \< 80 mL through Week 104 using the Kaplan-Meier method. |
| Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period | Week 76 | Assessed using participant daily diary and MBL volume measured using the alkaline hematin method. Participants were deemed to be amenorrhoeic if one of the following criteria was met: No feminine products returned due to reported amenorrhea, or No feminine products returned due to reported spotting or feminine product collection with a negligible observed MBL volume (\<5 mL) coupled with other data indicating infrequent non-cyclic bleeding/spotting. If no feminine product collection because participant failed to collect used products per protocol or due to Other reason, the amenorrhea status was set to missing. Missing responses for menstrual bleeding questions in the paper diary were treated as No Bleeding if paper diary entry/compliance rate was \>70%. |
| Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period | Week 52/Baseline to Week 76 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. Participants with amenorrhea are assigned with an MBL value of 0 mL and participants with spotting are assigned with an MBL value of 4.99 mL. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. |
| Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period | Week 52/Baseline to Week 104 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. Participants with amenorrhea are assigned with an MBL value of 0 mL and participants with spotting are assigned with an MBL value of 4.99 mL. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. |
| Percentage Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period | Week 52/Baseline to Week 76 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. Participants with amenorrhea are assigned with an MBL value of 0 mL and participants with spotting are assigned with an MBL value of 4.99 mL. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. |
| Percentage Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period | Week 52/Baseline to Week 104 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. Participants with amenorrhea are assigned with an MBL value of 0 mL and participants with spotting are assigned with an MBL value of 4.99 mL. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. |
| Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 104 During The Randomized Treatment Period | Week 104 | Assessed using participant daily diary and MBL volume measured using the alkaline hematin method. Participants were deemed to be amenorrhoeic if one of the following criteria was met: No feminine products returned due to reported amenorrhea or no feminine products returned due to reported spotting or feminine product collection with a negligible observed MBL volume (\<5 mL) coupled with other data indicating infrequent non-cyclic bleeding/spotting. If no feminine product collection because participant failed to collect used products per protocol or due to Other reason, the amenorrhea status was set to missing. Missing responses for menstrual bleeding questions in the paper diary were treated as No Bleeding if paper diary entry/compliance rate was \>70%. |
| Percentage Of Participants Who Responded (MBL Volume <80 mL) To Retreatment During The Retreatment Period | From Initiation of Retreatment to Week 104 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. |
| Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period | Week 52/Baseline to Week 76 and Week 104 | Participants who were previously amenorrhoeic were deemed to resume menses according to the following rules: MBL volume of collected feminine product was ≥5 mL; MBL volume of collected feminine product was \<5 mL; however, there were more than 5 days and more than 3 consecutive days of bleeding with feminine product use during the visit; no feminine products were returned because the participant failed to collect used products per protocol; however, there were more than 5 days and more than 3 consecutive days of bleeding with feminine product use during the visit; or no feminine products were returned due to other reasons that indicated menstruation had occurred; also, there were more than 5 days and more than 3 consecutive days of bleeding with feminine product use during the visit. |
| Time To Resumption Of Menses For Participants Who Were Amenorrhoeic At Week 52/Baseline During The Randomized Treatment Period | Week 52/Baseline up to Week 104 | Assessed using participant daily diary. Participants were deemed to be amenorrhoeic if one of the following criteria was met: No feminine products returned due to reported amenorrhea, or No feminine products returned due to reported spotting or feminine product collection with a negligible observed MBL volume (\<5 mL) coupled with other data indicating infrequent non-cyclic bleeding/spotting. If no feminine product collection because participant failed to collect used products per protocol or due to Other reason, the amenorrhea status was set to missing. Missing responses for menstrual bleeding questions in the paper diary were treated as No Bleeding if paper diary entry/compliance rate was \>70%. |
| Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | Week 52/Baseline to Week 76 | Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points. |
| Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period | From Week 52/Baseline to Week 76 and Week 104 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. |
| Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | Week 52/Baseline to Week 64 | Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points. |
| Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period | Week 52/Baseline to Week 76 | Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points. |
| Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period | Week 52/Baseline to Week 76 | Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points. |
| Time To MBL Volume ≥80 mL During The Randomized Treatment Period | From Week 52/Baseline through Week 104 | MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. |
| Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | Week 52/Baseline to Week 76 | The Short-Form Health Survey Standard (SF-36) is a validated, 36-item questionnaire, assessing general overall quality of life and was completed by participants on paper before other study procedures were performed, except for at the Week 52/Baseline visit, which was completed after eligibility for this study was confirmed and all Week 52 procedures for the long-term extension study were completed. Scores are calculated for each domain and 2 summary scores - a physical component summary (PCS) score (Domains \[number of items\]: Physical Functioning \[10\], Role-Physical \[4\], Bodily Pain \[2\], General Health \[5\]), a mental component summary (MCS) score (Domains \[number of items\]: Vitality \[4\], Social Functioning \[2\], Role-Emotional \[3\], and Mental Health \[5\]), and reported Health Transition \[1\]. Individual domain and component summary scores range from 0 to 100. Higher scores indicate higher health-related quality of life. |
| Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | Week 52/Baseline to Week 76 | The PGA for function is a 1-item questionnaire designed to assess participant's impression of the impact on their function related to uterine fibroids affected their usual activities and was completed on paper. The PGA for function was evaluated using a 5-point Likert scale (1 = No limitation at all; 5 = Extreme limitation) with higher numbers representing worse results. Endpoint values represent the worsening of function (deterioration), improvement of function (improvement), or no change by category at each time point. For example, a 4-category deterioration represents a change from 1 (No limitation at all) to 5 (Extreme limitation) and a 4-category improvement represents a change from 5 (Extreme limitation) to 1 (No limitation at all). |
| Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | Week 52/Baseline to Week 76 | 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 and was completed on paper. The PGA for symptoms was evaluated using a 5-point Likert scale (1 = Not severe; 5 = Extremely severe) with higher numbers representing worse results. Endpoint values represent the worsening of symptoms (deterioration), improvement of symptoms (improvement), or no change by category at each time point. For example, a 4-category deterioration represents a change from 1 (Not severe) to 5 (Extremely severe) and a 4-category improvement represents a change from 5 (Extremely severe) to 1 (Not severe). |
| Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | Week 52/Baseline up to Week 76 | The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent work time missed due to uterine fibroids was calculated from hours missed due to uterine fibroids divided by the sum of hours missed due to uterine fibroids plus hours actually worked. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes. |
| Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | Week 52/Baseline up to Week 76 | The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent impairment while working due to uterine fibroid symptoms was calculated by taking the reported value from 1 (no effect) to 10 (completely prevented work) and dividing by 10. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes. |
| Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | Week 52/Baseline up to Week 76 | The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent overall work impairment due to uterine fibroid symptoms was calculated from the work time missed due to uterine fibroids plus the value calculated from 1 minus the work time missed value multiplied by the value for impairment while working due to uterine fibroids. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes. |
| Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | Week 52/Baseline up to Week 76 | The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent activity impairment due to uterine fibroid symptoms was calculated by taking the reported value from 1 (no effect) to 10 (completely prevented activity) and dividing by 10. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes. |
| Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period | Week 52/Baseline to Week 76 | Assessed using the UFS-QOL which is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. The UFS-QoL was completed on a paper questionnaire and participants were to answer the following questions: heavy bleeding during your menstrual period (Question 1), passing blood clots during your menstrual period (Question 2), and feeling tightness or pressure in your pelvic area (Question 5). Items are scored on a 5-point scale, ranging from not at all to a very great deal. A summed score was created for questions 1, 2, and 5 and transformed to a normalized score with a range of possible values from 0 to 100, where a higher score was indicative of greater distress and a lower score of less distress (high scores = bad). |
| Original: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period | Week 52/Baseline to Week 76 | Assessed using the UFS-QOL, which is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. The UFS-QoL was completed on a paper questionnaire and participants were to answer these questions. Items are scored on a 5-point scale, ranging from not at all to a very great deal. A summed score was created for questions 1 through 8 and transformed to a normalized score with a range of possible values from 0 to 100, where a higher score was indicative of greater symptom severity and a lower score of lower symptom severity (negative score = improvement). |
| New: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period | Week 52/Baseline to Week 104 | Assessed using the UFS-QOL, which is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. The UFS-QoL was completed on a paper questionnaire and participants were to answer these questions. Items are scored on a 5-point scale, ranging from not at all to a very great deal. A summed score was created for questions 1 through 8 and transformed to a normalized score with a range of possible values from 0 to 100, where a higher score was indicative of greater symptom severity and a lower score of lower symptom severity (negative score = improvement). |
| Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Week 52/Baseline to Week 76 | Assessed using the UFS-QOL which, is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. Items are scored on a 5-point scale, ranging from none of the time to all of the time. The UFS-QoL was completed on a paper questionnaire and participants were to answer these questions. Questions 9 through 37 were used to calculate the total scores and the following subscales: concern, activities, revised activities, energy/mood, control, self-conscious, and sexual function. All raw scores are transformed to normalized scores with a range of possible values from 0 to 100. A positive score indicates improvement. |
| Predose Concentration Of Estradiol At Week 56 | Week 52/Baseline and Week 56 | Blood samples were collected from participants for estradiol measurements and were analyzed using a standard clinical methodology. The change from Week 52/Baseline in estradiol concentration at Week 56 was presented in this outcome. |
| Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Week 52/Baseline up to Week 104 | Assessed by percentage of participants with AEs and serious AEs (SAEs). An AE was defined as any 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. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or a congenital anomaly/birth defect. Events of heavy menstrual bleeding were only reported if the event met criteria as an SAE. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
| Percent Change From Week 52/Baseline In BMD At Lumbar Spine (L1-L4) | Week 52/Baseline to Week 104 | Assessed by dual-energy X-ray absorptiometry scan at the lumbar spine (L1-L4), total hip \[presented separately\], and femoral neck (same leg within each participant) \[presented separately\] at each designated timepoints. The least squares means and their 95% CI were based on analysis of covariance model with treatment, stratification factors, race as fixed factors, and age at Week 52/Baseline, Week 52/Baseline BMD value, and body mass index at Week 52/Baseline as covariates. |
| Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip | Week 52/Baseline to Week 104 | Assessed by dual-energy X-ray absorptiometry scan at the lumbar spine (L1-L4) \[presented separately\], total hip, and femoral neck (same leg within each participant) at each designated timepoints. The least squares means and their 95% CI were based on analysis of covariance model with treatment, stratification factors, race as fixed factors, and age at Week 52/Baseline, Week 52/Baseline BMD value, and body mass index at Week 52/Baseline as covariates. |
| Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Week 52/Baseline to Week 76 | The Short-Form Health Survey Standard (SF-36) is a validated, 36-item questionnaire, assessing general overall quality of life and was completed by participants on paper before other study procedures were performed, except for at the Week 52/Baseline visit, which was completed after eligibility for this study was confirmed and all Week 52 procedures for the long-term extension study were completed. Scores are calculated for each domain and 2 summary scores - a physical component summary score (Domains \[number of items\]: Physical Functioning \[10\], Role-Physical \[4\], Bodily Pain \[2\], General Health \[5\]), a mental component summary score (Domains \[number of items\]: Vitality \[4\], Social Functioning \[2\], Role-Emotional \[3\], and Mental Health \[5\]), and reported Health Transition \[1\]. Individual domain and component summary scores range from 0 to 100. Higher scores indicate higher health-related quality of life. |
Countries
Brazil, Chile, Czechia, Hungary, Italy, Poland, South Africa, United States
Participant flow
Recruitment details
Participants who completed the long-term extension study with a response to treatment, signed the informed consent form, and met all eligibility criteria were enrolled in the study.
Pre-assignment details
One participant in the placebo group was randomized in error and did not receive treatment, therefore, not included in the modified intent-to-treat (mITT) population.
Participants by arm
| Arm | Count |
|---|---|
| Relugolix Plus E2/NETA (Group A) Relugolix 40 mg co-administered with E2 (1 mg) and NETA (0.5 mg) for up to 52 weeks. | 115 |
| Placebo (Group B) Relugolix placebo co-administered with E2 and NETA placebo for up to 52 weeks. | 113 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 6 | 4 |
| Overall Study | Other | 9 | 9 |
| Overall Study | Participants who did not receive any study drug | 0 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Deviation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 8 |
Baseline characteristics
| Characteristic | Relugolix Plus E2/NETA (Group A) | Placebo (Group B) | Total |
|---|---|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 5.58 | 44.2 years STANDARD_DEVIATION 4.39 | 43.8 years STANDARD_DEVIATION 5.04 |
| Bone Mineral Density (BMD) at Week 52/Baseline Femoral neck | 0.97 g/cm^2 STANDARD_DEVIATION 0.186 | 0.97 g/cm^2 STANDARD_DEVIATION 0.164 | 0.97 g/cm^2 STANDARD_DEVIATION 0.175 |
| Bone Mineral Density (BMD) at Week 52/Baseline Lumbar Spine (L1-L4) | 1.18 g/cm^2 STANDARD_DEVIATION 0.173 | 1.20 g/cm^2 STANDARD_DEVIATION 0.147 | 1.19 g/cm^2 STANDARD_DEVIATION 0.16 |
| Bone Mineral Density (BMD) at Week 52/Baseline Total hip | 1.04 g/cm^2 STANDARD_DEVIATION 0.151 | 1.04 g/cm^2 STANDARD_DEVIATION 0.14 | 1.04 g/cm^2 STANDARD_DEVIATION 0.145 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 29 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 85 Participants | 84 Participants | 169 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Hemoglobin at Week 52/Baseline | 13.00 g/dL STANDARD_DEVIATION 1.405 | 12.81 g/dL STANDARD_DEVIATION 1.305 | 12.91 g/dL STANDARD_DEVIATION 1.356 |
| Index uterine fibroid volume at Week 52/Baseline | 40.06 cm^3 STANDARD_DEVIATION 59.093 | 70.36 cm^3 STANDARD_DEVIATION 142.863 | 55.01 cm^3 STANDARD_DEVIATION 109.619 |
| Mean Menstrual Blood Loss (MBL) Volume at Week 52/ Baseline | 8.67 mL STANDARD_DEVIATION 30.943 | 6.40 mL STANDARD_DEVIATION 20.073 | 7.55 mL STANDARD_DEVIATION 26.095 |
| Patient Global Assessment (PGA) for uterine fibroid-related function at Week 52/Baseline Extreme limitation | 3 Participants | 2 Participants | 5 Participants |
| Patient Global Assessment (PGA) for uterine fibroid-related function at Week 52/Baseline Mild limitation | 12 Participants | 10 Participants | 22 Participants |
| Patient Global Assessment (PGA) for uterine fibroid-related function at Week 52/Baseline Moderate limitation | 4 Participants | 5 Participants | 9 Participants |
| Patient Global Assessment (PGA) for uterine fibroid-related function at Week 52/Baseline No limitation at all | 94 Participants | 94 Participants | 188 Participants |
| Patient Global Assessment (PGA) for uterine fibroid-related function at Week 52/Baseline Quite a bit of limitation | 2 Participants | 2 Participants | 4 Participants |
| PGA for uterine fibroid-related symptom at Week 52/Baseline Extremely severe | 2 Participants | 3 Participants | 5 Participants |
| PGA for uterine fibroid-related symptom at Week 52/Baseline Mildly severe | 6 Participants | 7 Participants | 13 Participants |
| PGA for uterine fibroid-related symptom at Week 52/Baseline Moderately severe | 6 Participants | 4 Participants | 10 Participants |
| PGA for uterine fibroid-related symptom at Week 52/Baseline Not severe | 99 Participants | 97 Participants | 196 Participants |
| PGA for uterine fibroid-related symptom at Week 52/Baseline Very severe | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 49 Participants | 57 Participants | 106 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 63 Participants | 52 Participants | 115 Participants |
| Region of Enrollment Brazil | 5 participants | 2 participants | 7 participants |
| Region of Enrollment Chile | 3 participants | 8 participants | 11 participants |
| Region of Enrollment Czechia | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Hungary | 4 participants | 8 participants | 12 participants |
| Region of Enrollment Italy | 6 participants | 3 participants | 9 participants |
| Region of Enrollment Poland | 14 participants | 12 participants | 26 participants |
| Region of Enrollment South Africa | 7 participants | 6 participants | 13 participants |
| Region of Enrollment United States | 74 participants | 74 participants | 148 participants |
| Sex/Gender, Customized Female | 115 Participants | 113 Participants | 228 Participants |
| UFS-QoL Bleeding and Pelvic Discomfort (BPD) Scale Score at Week 52/Baseline | 10.51 score on a scale STANDARD_DEVIATION 17.138 | 15.12 score on a scale STANDARD_DEVIATION 24.027 | 12.79 score on a scale STANDARD_DEVIATION 20.921 |
| UFS-QoL Symptom Severity Score at Week 52/Baseline | 14.62 score on a scale STANDARD_DEVIATION 18.346 | 18.36 score on a scale STANDARD_DEVIATION 22.659 | 16.47 score on a scale STANDARD_DEVIATION 20.636 |
| Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) Total Score at Week 52/Baseline | 86.07 scores on a scale STANDARD_DEVIATION 18.566 | 81.06 scores on a scale STANDARD_DEVIATION 21.971 | 83.59 scores on a scale STANDARD_DEVIATION 20.435 |
| Uterine Volume at Week 52/Baseline | 274.95 cm^3 STANDARD_DEVIATION 201.122 | 324.98 cm^3 STANDARD_DEVIATION 309.228 | 299.75 cm^3 STANDARD_DEVIATION 261.001 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 116 | 0 / 112 |
| other Total, other adverse events | 29 / 116 | 45 / 112 |
| serious Total, serious adverse events | 2 / 116 | 2 / 112 |
Outcome results
Primary
Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. The sustained responder rate was calculated as the Kaplan-Meier estimate of the cumulative probability of MBL volume \< 80 mL through Week 76 using the Kaplan-Meier method.
Time frame: Week 52/Baseline up to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period | 78.43 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period | 15.08 percentage of participants |
Comparison: The primary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate.p-value: <0.000195% CI: [52.85, 73.86]Log-Log transformation
Secondary
Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period
The PGA for function is a 1-item questionnaire designed to assess participant's impression of the impact on their function related to uterine fibroids affected their usual activities and was completed on paper. The PGA for function was evaluated using a 5-point Likert scale (1 = No limitation at all; 5 = Extreme limitation) with higher numbers representing worse results. Endpoint values represent the worsening of function (deterioration), improvement of function (improvement), or no change by category at each time point. For example, a 4-category deterioration represents a change from 1 (No limitation at all) to 5 (Extreme limitation) and a 4-category improvement represents a change from 5 (Extreme limitation) to 1 (No limitation at all).
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 4 Category deterioration | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 3 Category deterioration | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 2 Category deterioration | 3 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 1 Category deterioration | 4 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | No change | 54 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 2 Category improvement | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 3 Category improvement | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 4 Category improvement | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 1 Category improvement | 2 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | No change | 7 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 4 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 1 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 3 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 3 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 2 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 2 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 1 Category deterioration | 1 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 4 Category improvement | 0 Participants |
Secondary
Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period
The PGA for function is a 1-item questionnaire designed to assess participant's impression of the impact on their function related to uterine fibroids affected their usual activities and was completed on paper. The PGA for function was evaluated using a 5-point Likert scale (1 = No limitation at all; 5 = Extreme limitation) with higher numbers representing worse results. Endpoint values represent the worsening of function (deterioration), improvement of function (improvement), or no change by category at each time point. For example, a 4-category deterioration represents a change from 1 (No limitation at all) to 5 (Extreme limitation) and a 4-category improvement represents a change from 5 (Extreme limitation) to 1 (No limitation at all).
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 4 Category deterioration | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 3 Category deterioration | 2 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 2 Category deterioration | 4 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | No change | 63 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 1 Category improvement | 5 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 2 Category improvement | 2 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 3 Category improvement | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 4 Category improvement | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 1 Category deterioration | 8 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 1 Category improvement | 1 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 4 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 3 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 2 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 2 Category deterioration | 3 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 1 Category deterioration | 3 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 4 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | No change | 14 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period | 3 Category improvement | 0 Participants |
Secondary
Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period
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 and was completed on paper. The PGA for symptoms was evaluated using a 5-point Likert scale (1 = Not severe; 5 = Extremely severe) with higher numbers representing worse results. Endpoint values represent the worsening of symptoms (deterioration), improvement of symptoms (improvement), or no change by category at each time point. For example, a 4-category deterioration represents a change from 1 (Not severe) to 5 (Extremely severe) and a 4-category improvement represents a change from 5 (Extremely severe) to 1 (Not severe).
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 2 Category deterioration | 4 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 2 Category improvement | 4 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | No change | 63 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 3 Category improvement | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 1 Category deterioration | 8 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 4 Category improvement | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 3 Category deterioration | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 1 Category improvement | 5 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 4 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 4 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 4 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 2 Category deterioration | 3 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 1 Category deterioration | 3 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | No change | 13 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 1 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 2 Category improvement | 1 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 3 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 3 Category deterioration | 1 Participants |
Secondary
Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period
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 and was completed on paper. The PGA for symptoms was evaluated using a 5-point Likert scale (1 = Not severe; 5 = Extremely severe) with higher numbers representing worse results. Endpoint values represent the worsening of symptoms (deterioration), improvement of symptoms (improvement), or no change by category at each time point. For example, a 4-category deterioration represents a change from 1 (Not severe) to 5 (Extremely severe) and a 4-category improvement represents a change from 5 (Extremely severe) to 1 (Not severe).
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 4 Category deterioration | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 3 Category deterioration | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 1 Category deterioration | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | No change | 58 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 1 Category improvement | 2 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 2 Category improvement | 2 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 3 Category improvement | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 4 Category improvement | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 2 Category deterioration | 1 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 4 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 4 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 1 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 3 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 2 Category deterioration | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 3 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 1 Category deterioration | 1 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | 2 Category improvement | 0 Participants |
| Placebo (Group B) | Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period | No change | 7 Participants |
Secondary
Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | 0.3 g/dL | Standard Deviation 0.96 |
| Placebo (Group B) | Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | -0.1 g/dL | Standard Deviation 1.1 |
Secondary
Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | 0.3 g/dL | Standard Deviation 1.03 |
| Placebo (Group B) | Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | -0.2 g/dL | Standard Deviation 1.36 |
Secondary
Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period
The Short-Form Health Survey Standard (SF-36) is a validated, 36-item questionnaire, assessing general overall quality of life and was completed by participants on paper before other study procedures were performed, except for at the Week 52/Baseline visit, which was completed after eligibility for this study was confirmed and all Week 52 procedures for the long-term extension study were completed. Scores are calculated for each domain and 2 summary scores - a physical component summary (PCS) score (Domains \[number of items\]: Physical Functioning \[10\], Role-Physical \[4\], Bodily Pain \[2\], General Health \[5\]), a mental component summary (MCS) score (Domains \[number of items\]: Vitality \[4\], Social Functioning \[2\], Role-Emotional \[3\], and Mental Health \[5\]), and reported Health Transition \[1\]. Individual domain and component summary scores range from 0 to 100. Higher scores indicate higher health-related quality of life.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | MCS | 0.2 score on a scale | Standard Deviation 7.93 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | PCS | 0.6 score on a scale | Standard Deviation 4.89 |
| Placebo (Group B) | Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | PCS | -1.8 score on a scale | Standard Deviation 6 |
| Placebo (Group B) | Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | MCS | -0.8 score on a scale | Standard Deviation 7.7 |
Secondary
Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period
The Short-Form Health Survey Standard (SF-36) is a validated, 36-item questionnaire, assessing general overall quality of life and was completed by participants on paper before other study procedures were performed, except for at the Week 52/Baseline visit, which was completed after eligibility for this study was confirmed and all Week 52 procedures for the long-term extension study were completed. Scores are calculated for each domain and 2 summary scores - a physical component summary (PCS) score (Domains \[number of items\]: Physical Functioning \[10\], Role-Physical \[4\], Bodily Pain \[2\], General Health \[5\]), a mental component summary (MCS) score (Domains \[number of items\]: Vitality \[4\], Social Functioning \[2\], Role-Emotional \[3\], and Mental Health \[5\]), and reported Health Transition \[1\]. Individual domain and component summary scores range from 0 to 100. Higher scores indicate higher health-related quality of life.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | PCS | 0.8 score on a scale | Standard Deviation 5.18 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | MCS | -0.8 score on a scale | Standard Deviation 6.65 |
| Placebo (Group B) | Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | PCS | -0.6 score on a scale | Standard Deviation 4.04 |
| Placebo (Group B) | Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period | MCS | 0.1 score on a scale | Standard Deviation 7.71 |
Secondary
Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period
The Short-Form Health Survey Standard (SF-36) is a validated, 36-item questionnaire, assessing general overall quality of life and was completed by participants on paper before other study procedures were performed, except for at the Week 52/Baseline visit, which was completed after eligibility for this study was confirmed and all Week 52 procedures for the long-term extension study were completed. Scores are calculated for each domain and 2 summary scores - a physical component summary score (Domains \[number of items\]: Physical Functioning \[10\], Role-Physical \[4\], Bodily Pain \[2\], General Health \[5\]), a mental component summary score (Domains \[number of items\]: Vitality \[4\], Social Functioning \[2\], Role-Emotional \[3\], and Mental Health \[5\]), and reported Health Transition \[1\]. Individual domain and component summary scores range from 0 to 100. Higher scores indicate higher health-related quality of life.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Role-Physical | 0.3 score on a scale | Standard Deviation 4.8 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Social Functioning | -0.2 score on a scale | Standard Deviation 7.85 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | General Health | 0 score on a scale | Standard Deviation 6.68 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Role-Emotional | 0.6 score on a scale | Standard Deviation 7.38 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Bodily Pain | 0.6 score on a scale | Standard Deviation 8.02 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Mental Health | 0.5 score on a scale | Standard Deviation 8.3 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Vitality | 0.5 score on a scale | Standard Deviation 7.87 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Physical Functioning | 1.1 score on a scale | Standard Deviation 4.24 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Physical Functioning | -2.3 score on a scale | Standard Deviation 5.16 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Role-Physical | -1.2 score on a scale | Standard Deviation 4.75 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Bodily Pain | -0.3 score on a scale | Standard Deviation 9.78 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | General Health | -3.1 score on a scale | Standard Deviation 6.81 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Vitality | 0.4 score on a scale | Standard Deviation 8.83 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Social Functioning | -2.9 score on a scale | Standard Deviation 6.65 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Role-Emotional | -1.0 score on a scale | Standard Deviation 7.23 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Mental Health | -1.0 score on a scale | Standard Deviation 9.98 |
Secondary
Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period
The Short-Form Health Survey Standard (SF-36) is a validated, 36-item questionnaire, assessing general overall quality of life and was completed by participants on paper before other study procedures were performed, except for at the Week 52/Baseline visit, which was completed after eligibility for this study was confirmed and all Week 52 procedures for the long-term extension study were completed. Scores are calculated for each domain and 2 summary scores - a physical component summary score (Domains \[number of items\]: Physical Functioning \[10\], Role-Physical \[4\], Bodily Pain \[2\], General Health \[5\]), a mental component summary score (Domains \[number of items\]: Vitality \[4\], Social Functioning \[2\], Role-Emotional \[3\], and Mental Health \[5\]), and reported Health Transition \[1\]. Individual domain and component summary scores range from 0 to 100. Higher scores indicate higher health-related quality of life.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Physical Functioning | 0.5 score on a scale | Standard Deviation 5.44 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Role-Physical | -0.5 score on a scale | Standard Deviation 6.49 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | General Health | -0.6 score on a scale | Standard Deviation 5.67 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Vitality | 0.5 score on a scale | Standard Deviation 7.53 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Role-Emotional | -0.2 score on a scale | Standard Deviation 7.32 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Mental Health | -0.8 score on a scale | Standard Deviation 7.34 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Bodily Pain | 1.9 score on a scale | Standard Deviation 7.36 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Social Functioning | -0.4 score on a scale | Standard Deviation 7.85 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Social Functioning | -0.6 score on a scale | Standard Deviation 3.21 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Physical Functioning | 0.5 score on a scale | Standard Deviation 2.23 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Mental Health | 2.9 score on a scale | Standard Deviation 9.83 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Role-Physical | -0.6 score on a scale | Standard Deviation 2.88 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Bodily Pain | 1.7 score on a scale | Standard Deviation 8.42 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Role-Emotional | -3.9 score on a scale | Standard Deviation 6.29 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | General Health | -5.5 score on a scale | Standard Deviation 7.72 |
| Placebo (Group B) | Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period | Vitality | 3.0 score on a scale | Standard Deviation 8.84 |
Secondary
Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period
Assessed using the UFS-QOL which is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. The UFS-QoL was completed on a paper questionnaire and participants were to answer the following questions: heavy bleeding during your menstrual period (Question 1), passing blood clots during your menstrual period (Question 2), and feeling tightness or pressure in your pelvic area (Question 5). Items are scored on a 5-point scale, ranging from not at all to a very great deal. A summed score was created for questions 1, 2, and 5 and transformed to a normalized score with a range of possible values from 0 to 100, where a higher score was indicative of greater distress and a lower score of less distress (high scores = bad).
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period | -0.5 score on a scale | Standard Deviation 17.85 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period | -6.3 score on a scale | Standard Deviation 43.36 |
Secondary
Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period
Assessed using the UFS-QOL which is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. The UFS-QoL was completed on a paper questionnaire and participants were to answer the following questions: heavy bleeding during your menstrual period (Question 1), passing blood clots during your menstrual period (Question 2), and feeling tightness or pressure in your pelvic area (Question 5). Items are scored on a 5-point scale, ranging from not at all to a very great deal. A summed score was created for questions 1, 2, and 5 and transformed to a normalized score with a range of possible values from 0 to 100, where a higher score was indicative of greater distress and a lower score of less distress (high scores = bad).
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period | 3.4 score on a scale | Standard Deviation 20.27 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period | 17.5 score on a scale | Standard Deviation 24.99 |
Secondary
Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period
Assessed using the UFS-QOL which, is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. Items are scored on a 5-point scale, ranging from none of the time to all of the time. The UFS-QoL was completed on a paper questionnaire and participants were to answer these questions. Questions 9 through 37 were used to calculate the total scores and the following subscales: concern, activities, revised activities, energy/mood, control, self-conscious, and sexual function. All raw scores are transformed to normalized scores with a range of possible values from 0 to 100. A positive score indicates improvement.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Concern | 2.2 score on a scale | Standard Deviation 21.45 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Energy/mood | 1.6 score on a scale | Standard Deviation 17.41 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Control | 1.7 score on a scale | Standard Deviation 15.19 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Self-conscious | -2.8 score on a scale | Standard Deviation 19.94 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Total Score | 1.1 score on a scale | Standard Deviation 15.25 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Activities | 0.9 score on a scale | Standard Deviation 16.74 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Revised activities | 0.6 score on a scale | Standard Deviation 16.02 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Sexual function | 0.8 score on a scale | Standard Deviation 26.51 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Total Score | 8.2 score on a scale | Standard Deviation 42.12 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Concern | 11.9 score on a scale | Standard Deviation 41.4 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Activities | 8.5 score on a scale | Standard Deviation 42 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Revised activities | 7.5 score on a scale | Standard Deviation 42.59 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Self-conscious | 3.1 score on a scale | Standard Deviation 44.53 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Energy/mood | 8.0 score on a scale | Standard Deviation 44.35 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Sexual function | 3.1 score on a scale | Standard Deviation 52.08 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Control | 9.4 score on a scale | Standard Deviation 39.05 |
Secondary
Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period
Assessed using the UFS-QOL which, is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. Items are scored on a 5-point scale, ranging from none of the time to all of the time. The UFS-QoL was completed on a paper questionnaire and participants were to answer these questions. Questions 9 through 37 were used to calculate the total scores and the following subscales: concern, activities, revised activities, energy/mood, control, self-conscious, and sexual function. All raw scores are transformed to normalized scores with a range of possible values from 0 to 100. A positive score indicates improvement.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values for that measure at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Concern | -2.4 score on a scale | Standard Deviation 24.38 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Activities | -1.7 score on a scale | Standard Deviation 17.46 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Revised activities | -2.3 score on a scale | Standard Deviation 18.66 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Energy/mood | -0.1 score on a scale | Standard Deviation 17.3 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Control | 0.2 score on a scale | Standard Deviation 15.6 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Self-conscious | 0 score on a scale | Standard Deviation 21.66 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Sexual function | 1.0 score on a scale | Standard Deviation 28.77 |
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Total Score | -0.8 score on a scale | Standard Deviation 16.79 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Control | -3.6 score on a scale | Standard Deviation 23.03 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Concern | -13.6 score on a scale | Standard Deviation 27.76 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Revised activities | -13.3 score on a scale | Standard Deviation 27.13 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Activities | -11.7 score on a scale | Standard Deviation 26.1 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Self-conscious | -11.5 score on a scale | Standard Deviation 16.77 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Sexual function | -16.7 score on a scale | Standard Deviation 43.72 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Energy/mood | -3.9 score on a scale | Standard Deviation 23.69 |
| Placebo (Group B) | Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period | Total Score | -9.1 score on a scale | Standard Deviation 22.37 |
Secondary
Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent activity impairment due to uterine fibroid symptoms was calculated by taking the reported value from 1 (no effect) to 10 (completely prevented activity) and dividing by 10. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes.
Time frame: Week 52/Baseline up to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | -0.5 percentage score | Standard Deviation 21.1 |
| Placebo (Group B) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 4.5 percentage score | Standard Deviation 19.32 |
Secondary
Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent activity impairment due to uterine fibroid symptoms was calculated by taking the reported value from 1 (no effect) to 10 (completely prevented work) and dividing by 10. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages (0 to 100%), with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes.
Time frame: Week 52/Baseline up to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | -1.3 percentage score | Standard Deviation 18.9 |
| Placebo (Group B) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 5.0 percentage score | Standard Deviation 10.69 |
Secondary
Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent impairment while working due to uterine fibroid symptoms was calculated by taking the reported value from 1 (no effect) to 10 (completely prevented work) and dividing by 10. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes.
Time frame: Week 52/Baseline up to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | -1.1 percentage score | Standard Deviation 16.2 |
| Placebo (Group B) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 1.8 percentage score | Standard Deviation 15.9 |
Secondary
Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent impairment while working due to uterine fibroid symptoms was calculated by taking the reported value from 1 (no effect) to 10 (completely prevented work) and dividing by 10. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes.
Time frame: Week 52/Baseline up to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 0 percentage score | Standard Deviation 15.17 |
| Placebo (Group B) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 5.0 percentage score | Standard Deviation 12.25 |
Secondary
Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent overall work impairment due to uterine fibroid symptoms was calculated from the work time missed due to uterine fibroids plus the value calculated from 1 minus the work time missed value multiplied by the value for impairment while working due to uterine fibroids. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes.
Time frame: Week 52/Baseline up to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | -0.8 percentage score | Standard Deviation 20.05 |
| Placebo (Group B) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 3.2 percentage score | Standard Deviation 10.56 |
Secondary
Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent overall work impairment due to uterine fibroid symptoms was calculated from the work time missed due to uterine fibroids plus the value calculated from 1 minus the work time missed value multiplied by the value for impairment while working due to uterine fibroids. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes.
Time frame: Week 52/Baseline up to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 0.6 percentage score | Standard Deviation 19.13 |
| Placebo (Group B) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 6.0 percentage score | Standard Deviation 13.42 |
Secondary
Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent work time missed due to uterine fibroids was calculated from hours missed due to uterine fibroids divided by the sum of hours missed due to uterine fibroids plus hours actually worked. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes.
Time frame: Week 52/Baseline up to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 0.7 percentage score | Standard Deviation 10.22 |
| Placebo (Group B) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 3.9 percentage score | Standard Deviation 13.85 |
Secondary
Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
The WPAI-UF is a validated instrument used to measure self-reported absenteeism, presenteeism, and daily activity impairment attributed to uterine fibroids. The WPAI-UF was to be completed on a paper questionnaire and participants were to answer these questions. Percent work time missed due to uterine fibroids was calculated from hours missed due to uterine fibroids divided by the sum of hours missed due to uterine fibroids plus hours actually worked. This value was then multiplied by 100 to get a percentage. The WPAI-UF outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity due to uterine fibroids, that is, worse outcomes.
Time frame: Week 52/Baseline up to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 0.5 percentage score | Standard Deviation 8.5 |
| Placebo (Group B) | Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period | 0 percentage score | Standard Deviation 0 |
Secondary
Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. Participants with amenorrhea are assigned with an MBL value of 0 mL and participants with spotting are assigned with an MBL value of 4.99 mL. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period | 2.1 mL | Standard Deviation 28.85 |
| Placebo (Group B) | Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period | 3.9 mL | Standard Deviation 10.92 |
Secondary
Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. Participants with amenorrhea are assigned with an MBL value of 0 mL and participants with spotting are assigned with an MBL value of 4.99 mL. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period | 6.6 mL | Standard Deviation 42.8 |
| Placebo (Group B) | Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period | 11.5 mL | Standard Deviation 27.45 |
Secondary
New: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period
Assessed using the UFS-QOL, which is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. The UFS-QoL was completed on a paper questionnaire and participants were to answer these questions. Items are scored on a 5-point scale, ranging from not at all to a very great deal. A summed score was created for questions 1 through 8 and transformed to a normalized score with a range of possible values from 0 to 100, where a higher score was indicative of greater symptom severity and a lower score of lower symptom severity (negative score = improvement).
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | New: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period | 0.1 score on a scale | Standard Deviation 15.94 |
| Placebo (Group B) | New: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period | -4.3 score on a scale | Standard Deviation 42.22 |
Secondary
Original: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period
Assessed using the UFS-QOL, which is a validated instrument used to evaluate symptom severity and quality of life in participants with uterine fibroids. The UFS-QoL was completed on a paper questionnaire and participants were to answer these questions. Items are scored on a 5-point scale, ranging from not at all to a very great deal. A summed score was created for questions 1 through 8 and transformed to a normalized score with a range of possible values from 0 to 100, where a higher score was indicative of greater symptom severity and a lower score of lower symptom severity (negative score = improvement).
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Original: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period | 2.2 score on a scale | Standard Deviation 18.16 |
| Placebo (Group B) | Original: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period | 14.1 score on a scale | Standard Deviation 21.07 |
Secondary
Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability
Assessed by percentage of participants with AEs and serious AEs (SAEs). An AE was defined as any 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. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or a congenital anomaly/birth defect. Events of heavy menstrual bleeding were only reported if the event met criteria as an SAE. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Week 52/Baseline up to Week 104
Population: Safety population: all randomized participants who received at least 1 dose of study treatment. Note: One patient who was randomized to the placebo group was inadvertently dispensed open-label study drug of which the patient took 1 dose of relugolix + E2/NETA. Thus, the patient was considered as part of the relugolix + E2/NETA group in the Safety Population only. This changes the Group A population from 115 (mITT population) to 116 and the Group B population from 113 (mITT population) to 112.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Any AEs | 68 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Leading to study treatment discontinuation | 2 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Leading to study treatment interruption | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Related to study drug | 26 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Grade 3 or higher | 3 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Grade 3 or higher related to study drug | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | SAEs | 2 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Serious and related to study drug | 0 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Serious and leading to treatment discontinuation | 1 Participants |
| Relugolix Plus E2/NETA (Group A) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Fatal outcome | 0 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Serious and leading to treatment discontinuation | 1 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Any AEs | 72 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Fatal outcome | 0 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Leading to study treatment discontinuation | 3 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Grade 3 or higher related to study drug | 2 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Leading to study treatment interruption | 0 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Serious and related to study drug | 1 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Related to study drug | 27 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | SAEs | 2 Participants |
| Placebo (Group B) | Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability | Grade 3 or higher | 5 Participants |
Secondary
Percentage Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. Participants with amenorrhea are assigned with an MBL value of 0 mL and participants with spotting are assigned with an MBL value of 4.99 mL. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all randomized participants who had taken at least 1 dose of study treatment. The % change from Week 52 in MBL volume was only available when Week 52 MBL volume is \> 0 mL and post-Week 52 MBL volumes were available. The majority of mITT participants had MBL volume of 0 mL at Week 52/Baseline (92/115 in Group A and 89/113 in Group B). Number analyzed represents proportion of mITT population with MBL volume \> 0 mL at Week 52 and values at each time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period | -42.0 percent change | Standard Deviation 48.8 |
Secondary
Percentage Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. Participants with amenorrhea are assigned with an MBL value of 0 mL and participants with spotting are assigned with an MBL value of 4.99 mL. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all randomized participants who had taken at least 1 dose of study treatment. The % change from Week 52 in MBL volume was only available when Week 52 MBL volume is \> 0 mL and post-Week 52 MBL volumes were available. The majority of mITT participants had MBL volume of 0 mL at Week 52/Baseline (92/115 in Group A and 89/113 in Group B). Number analyzed represents proportion of mITT population with MBL volume \> 0 mL at Week 52 and values at each time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period | 652.0 percent change | Standard Deviation 1759.37 |
| Placebo (Group B) | Percentage Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period | 55.0 percent change | Standard Deviation 219.15 |
Secondary
Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 104 During The Randomized Treatment Period
Assessed using participant daily diary and MBL volume measured using the alkaline hematin method. Participants were deemed to be amenorrhoeic if one of the following criteria was met: No feminine products returned due to reported amenorrhea or no feminine products returned due to reported spotting or feminine product collection with a negligible observed MBL volume (\<5 mL) coupled with other data indicating infrequent non-cyclic bleeding/spotting. If no feminine product collection because participant failed to collect used products per protocol or due to Other reason, the amenorrhea status was set to missing. Missing responses for menstrual bleeding questions in the paper diary were treated as No Bleeding if paper diary entry/compliance rate was \>70%.
Time frame: Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 104 During The Randomized Treatment Period | 58.26 percentage of patients |
| Placebo (Group B) | Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 104 During The Randomized Treatment Period | 10.62 percentage of patients |
Secondary
Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period
Assessed using participant daily diary and MBL volume measured using the alkaline hematin method. Participants were deemed to be amenorrhoeic if one of the following criteria was met: No feminine products returned due to reported amenorrhea, or No feminine products returned due to reported spotting or feminine product collection with a negligible observed MBL volume (\<5 mL) coupled with other data indicating infrequent non-cyclic bleeding/spotting. If no feminine product collection because participant failed to collect used products per protocol or due to Other reason, the amenorrhea status was set to missing. Missing responses for menstrual bleeding questions in the paper diary were treated as No Bleeding if paper diary entry/compliance rate was \>70%.
Time frame: Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA and placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period | 57.39 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period | 13.27 percentage of participants |
p-value: <0.000195% CI: [33.13, 55.11]Cochran-Mantel-Haenszel
Secondary
Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period | 4.94 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period | 10.00 percentage of participants |
Secondary
Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period | 5.08 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period | 0 percentage of participants |
Secondary
Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period | 6.78 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period | 25.00 percentage of participants |
Secondary
Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period | 6.17 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period | 15.00 percentage of participants |
Secondary
Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. The sustained responder rate was calculated as the Kaplan-Meier estimate of the cumulative probability of MBL volume \< 80 mL through Week 104 using the Kaplan-Meier method.
Time frame: Week 52/Baseline up to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period | 69.79 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period | 11.75 percentage of participants |
p-value: <0.000195% CI: [46.97, 69.11]Log-Log transformation
Secondary
Percentage Of Participants Who Responded (MBL Volume <80 mL) To Retreatment During The Retreatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding.
Time frame: From Initiation of Retreatment to Week 104
Population: Retreatment population: comprised participants in the mITT population from both treatment groups whose MBL volume reached ≥ 80 mL during the randomized treatment period and who started retreatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Who Responded (MBL Volume <80 mL) To Retreatment During The Retreatment Period | 96.15 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Who Responded (MBL Volume <80 mL) To Retreatment During The Retreatment Period | 97.75 percentage of participants |
Secondary
Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period
Participants who were previously amenorrhoeic were deemed to resume menses according to the following rules: MBL volume of collected feminine product was ≥5 mL; MBL volume of collected feminine product was \<5 mL; however, there were more than 5 days and more than 3 consecutive days of bleeding with feminine product use during the visit; no feminine products were returned because the participant failed to collect used products per protocol; however, there were more than 5 days and more than 3 consecutive days of bleeding with feminine product use during the visit; or no feminine products were returned due to other reasons that indicated menstruation had occurred; also, there were more than 5 days and more than 3 consecutive days of bleeding with feminine product use during the visit.
Time frame: Week 52/Baseline to Week 76 and Week 104
Population: mITT population who was amenorrhoeic at Week 52/Baseline: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo) and who were amenorrhoeic at Week 52/Baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period | Week 76 | 35.29 percentage of participants |
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period | Week 104 | 41.12 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period | Week 76 | 91.54 percentage of participants |
| Placebo (Group B) | Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period | Week 104 | 92.75 percentage of participants |
Secondary
Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding.
Time frame: From Week 52/Baseline to Week 76 and Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period | At Week 76 | 21.57 percentage of participants |
| Relugolix Plus E2/NETA (Group A) | Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period | At Week 104 | 30.21 percentage of participants |
| Placebo (Group B) | Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period | At Week 76 | 84.92 percentage of participants |
| Placebo (Group B) | Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period | At Week 104 | 88.25 percentage of participants |
Secondary
Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip
Assessed by dual-energy X-ray absorptiometry scan at the lumbar spine (L1-L4) \[presented separately\], total hip, and femoral neck (same leg within each participant) at each designated timepoints. The least squares means and their 95% CI were based on analysis of covariance model with treatment, stratification factors, race as fixed factors, and age at Week 52/Baseline, Week 52/Baseline BMD value, and body mass index at Week 52/Baseline as covariates.
Time frame: Week 52/Baseline to Week 104
Population: Safety population: all randomized participants who received at least 1 dose of study treatment. Note: 1 patient was randomized to placebo and inadvertently dispensed open-label study drug; the patient took 1 dose and was considered part of Group A in the Safety population only and is represented in the Overall Number of Participants Analyzed. Number analyzed by location/group represents proportion of the Safety population with values for that measure at that time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip | Total Hip | 0.34 percent change |
| Relugolix Plus E2/NETA (Group A) | Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip | Femoral Neck | -0.19 percent change |
| Placebo (Group B) | Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip | Total Hip | -0.13 percent change |
| Placebo (Group B) | Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip | Femoral Neck | -0.76 percent change |
Secondary
Percent Change From Week 52/Baseline In BMD At Lumbar Spine (L1-L4)
Assessed by dual-energy X-ray absorptiometry scan at the lumbar spine (L1-L4), total hip \[presented separately\], and femoral neck (same leg within each participant) \[presented separately\] at each designated timepoints. The least squares means and their 95% CI were based on analysis of covariance model with treatment, stratification factors, race as fixed factors, and age at Week 52/Baseline, Week 52/Baseline BMD value, and body mass index at Week 52/Baseline as covariates.
Time frame: Week 52/Baseline to Week 104
Population: Safety population: all randomized participants who received at least 1 dose of study treatment. Note: 1 patient was randomized to placebo and inadvertently dispensed open-label study drug; the patient took 1 dose and was considered part of Group A in the Safety population only and is represented in the Overall Number of Participants Analyzed. Number analyzed by location/group represents proportion of the Safety population with values for that measure at that time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percent Change From Week 52/Baseline In BMD At Lumbar Spine (L1-L4) | 0.81 percent change |
| Placebo (Group B) | Percent Change From Week 52/Baseline In BMD At Lumbar Spine (L1-L4) | 0.10 percent change |
Secondary
Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 76
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | 2.8 percent change | Standard Deviation 8.3 |
| Placebo (Group B) | Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | -0.8 percent change | Standard Deviation 9.1 |
Secondary
Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 64
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | 1.3 percent change | Standard Deviation 6.75 |
| Placebo (Group B) | Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | -4.3 percent change | Standard Deviation 8.53 |
Secondary
Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
Blood samples were collected from participants for hemoglobin measurements in accordance with the specified time points.
Time frame: Week 52/Baseline to Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo). Number analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | 2.3 percent change | Standard Deviation 8.94 |
| Placebo (Group B) | Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period | -0.7 percent change | Standard Deviation 10.65 |
Secondary
Predose Concentration Of Estradiol At Week 56
Blood samples were collected from participants for estradiol measurements and were analyzed using a standard clinical methodology. The change from Week 52/Baseline in estradiol concentration at Week 56 was presented in this outcome.
Time frame: Week 52/Baseline and Week 56
Population: Safety population: all randomized participants who received at least 1 dose of study treatment. Overall number of participants analyzed represents proportion of overall group with values at that time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Predose Concentration Of Estradiol At Week 56 | 2.03 pg/mL | Standard Deviation 31.605 |
| Placebo (Group B) | Predose Concentration Of Estradiol At Week 56 | 62.54 pg/mL | Standard Deviation 77.661 |
Secondary
Time To MBL Volume ≥80 mL During The Randomized Treatment Period
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding.
Time frame: From Week 52/Baseline through Week 104
Population: mITT population: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Time To MBL Volume ≥80 mL During The Randomized Treatment Period | NA weeks |
| Placebo (Group B) | Time To MBL Volume ≥80 mL During The Randomized Treatment Period | 5.9 weeks |
p-value: <0.000195% CI: [0.08, 0.2]Log Rank
Secondary
Time To Resumption Of Menses For Participants Who Were Amenorrhoeic At Week 52/Baseline During The Randomized Treatment Period
Assessed using participant daily diary. Participants were deemed to be amenorrhoeic if one of the following criteria was met: No feminine products returned due to reported amenorrhea, or No feminine products returned due to reported spotting or feminine product collection with a negligible observed MBL volume (\<5 mL) coupled with other data indicating infrequent non-cyclic bleeding/spotting. If no feminine product collection because participant failed to collect used products per protocol or due to Other reason, the amenorrhea status was set to missing. Missing responses for menstrual bleeding questions in the paper diary were treated as No Bleeding if paper diary entry/compliance rate was \>70%.
Time frame: Week 52/Baseline up to Week 104
Population: mITT population who was amenorrhoeic at Week 52/Baseline: all participants randomized to treatment who had taken at least 1 dose of study treatment (relugolix plus E2/NETA or placebo) and who were amenorrhoeic at Week 52/Baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Relugolix Plus E2/NETA (Group A) | Time To Resumption Of Menses For Participants Who Were Amenorrhoeic At Week 52/Baseline During The Randomized Treatment Period | NA weeks |
| Placebo (Group B) | Time To Resumption Of Menses For Participants Who Were Amenorrhoeic At Week 52/Baseline During The Randomized Treatment Period | 5.4 weeks |