Phase 3
N=382
LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Heavy Menstrual Bleeding · Uterine Fibroid
Bottom Line
View on ClinicalTrials.gov: NCT03103087 ↗Enrolled (actual)
382
Serious AEs
1.8%
Results posted
Apr 2022
Primary outcome: Primary: Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA — 71.2; 14.73 Percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Relugolix (Drug); Estradiol/norethindrone acetate (Drug); Relugolix placebo (Drug); Estradiol/norethindrone acetate placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Myovant Sciences GmbH
- Primary completion
- Jul 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA |
71.2; 14.73 | <0.0001 sig |
| SECONDARY Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment |
50.40; 3.10 | <0.0001 sig |
| SECONDARY Percent Change From Baseline At Week 24 In MBL Volume |
-84.3; -15.1 | <0.0001 sig |
| SECONDARY Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24 |
61.29; 5.41 | <0.0001 sig |
| SECONDARY Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment |
47.06; 17.07 | <0.0001 sig |
| SECONDARY Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume |
-17.4; -7.4 | =0.2153 |
| SECONDARY Percent Change From Baseline At Week 24 In Uterine Volume |
-13.8; -1.5 | =0.0078 sig |
| SECONDARY Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5) |
-51.7; -18.3 | <0.0001 sig |
| SECONDARY Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 to L4) As Assessed By DXA |
-0.819; -1.919 | — |
| SECONDARY Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck As Assessed By DXA |
-0.126; 0.315; -0.173; -0.044; -0.684; 0.019 | — |
| SECONDARY Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12 |
5.56; 35.71 | <0.0001 sig |
| SECONDARY Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24 |
6.3; 3.9 | — |
| SECONDARY Predose Trough Concentrations Of Relugolix And NET In The Relugolix Plus E2/NETA Group At Week 24 |
1.96; 0.28 | — |
| SECONDARY Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24 |
45.34 | — |
| SECONDARY Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group |
-22.30 | — |
| SECONDARY Time To MBL Response |
8.4; 27.1 | < 0.0001 sig |
| SECONDARY Sustained Amenorrhea Rate (No Or Negligible Bleeding) |
63; 4 | <0.0001 sig |
| SECONDARY Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding) |
16.3; NA | <0.0001 sig |
| SECONDARY Time To Achieving Amenorrhea (No Or Negligible Bleeding) |
8.9; NA | < 0.0001 sig |
| SECONDARY Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24 |
19; 2 | <0.0001 sig |
| SECONDARY Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline |
24.3; 4.3 | <0.0001 sig |
| SECONDARY Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal |
35; 18 | <0.0001 sig |
| SECONDARY Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score |
-36.1; -13.7 | <0.0001 sig |
| SECONDARY Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score |
43.6; 17.1 | <0.0001 sig |
| SECONDARY Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score |
44.4; 16.5 | <0.0001 sig |
| SECONDARY Change From Baseline In UFS-QoL Score by Health-Related Quality of Life Total Score |
37.8; 13.8 | <0.0001 sig |
| SECONDARY Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score |
78; 42 | <0.0001 sig |
| SECONDARY Change From Baseline in UFS-QoL Bleeding and Pelvic Discomfort Scale Score |
-51.7; -18.3 | <0.0001 sig |
| SECONDARY Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score |
79; 37 | <0.0001 sig |
| SECONDARY Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11 |
-2.0; -0.7 | <0.0001 sig |
| SECONDARY Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20 |
-1.8; -0.6 | <0.0001 sig |
| SECONDARY Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29 |
-1.4; -0.7 | — |
| SECONDARY Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire |
-2.0; -0.8 | <0.0001 sig |
| SECONDARY Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire |
-1.7; -0.8 | — |
| SECONDARY Participants Achieving Improvement From Baseline In PGA Questionnaire For Symptoms From Baseline At Week 24 |
7; 21; 22; 8; 29; 18 | — |
| SECONDARY Participants Achieving Improvement From Baseline In PGA For Uterine Fibroid-related Function From Baseline At Week 24 |
13; 19; 30; 13; 18; 10 | — |
| SECONDARY Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities |
-1.8; -0.9 | — |
| SECONDARY Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities |
-1.8; -1.0 | — |
| SECONDARY Number Of Participants Who Achieved A Maximum NRS Score ≤ 1 For Uterine Fibroid-associated Pain Over The Last 35 Days Of Treatment Who Had Maximum Pain Scores ≥ 4 During The 35 Days Prior To Randomization |
34; 17 | — |
| SECONDARY Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline |
48; 34 | 0.0004 sig |
| SECONDARY Change From Baseline In Luteinizing Serum Concentration At Week 24 |
-3.10; 3.04 | — |
| SECONDARY Change From Baseline In Follicle Stimulating Serum Concentration At Week 24 |
-5.47; -0.67 | — |
| SECONDARY Change From Baseline In E2 Serum Concentration At Week 24 |
-22.30; 39.85 | — |
| SECONDARY Change From Baseline In Progesterone Serum Concentration At Week 24 |
0.12; 3.48 | — |
Summary
The purpose of this study is to determine the benefit of relugolix 40 milligrams (mg) once a day co-administered with estradiol (E2) 1 mg and norethindrone acetate (NETA) 0.5 mg compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids.
Eligibility Criteria
Key Inclusion Criteria
- Premenopausal female aged 18 to 50 years old (inclusive) on the day of signing and dating the informed consent form.
- Has regularly occurring menstrual periods of ≤ 14 days duration with a cycle of 21 to 38 days from the start of 1 menstrual period until the start of the next, by participant history for at least 3 months prior to the first screening visit.
- Has a diagnosis of uterine fibroids that is confirmed by a transvaginal and/or transabdominal ultrasound performed during the screening period.
- Has heavy menstrual bleeding associated with uterine fibroids as evidenced by an MBL of ≥ 160 milliliter (mL) during 1 cycle or ≥ 80 mL per cycle for 2 menstrual cycles as measured by the alkaline hematin method during the screening period.
Key Exclusion Criteria
- Has transvaginal and/or transabdominal ultrasound during the screening period demonstrating pathology other than uterine fibroids that could be responsible for or contributing to the participant's heavy menstrual bleeding.
- Has known rapidly enlarging uterine fibroids in the opinion of the investigator.
- Has a weight that exceeds the weight limit of the DXA scanner or has a condition that precludes an adequate DXA measurement at the lumbar spine and proximal femur.
- Has a history of or currently has osteoporosis, or other metabolic bone disease, hyperparathyroidism, hyperprolactinemia, hyperthyroidism, anorexia nervosa, or low traumatic (from the standing position) or atraumatic fracture (toe, finger, skull, face and ankle fractures are allowed). A history of successfully treated hyperparathyroidism, hyperprolactinemia, or hyperthyroidism is allowed if the participant's bone mineral density is within normal limits.
- Has a history of the use of bisphosphonates, calcitonin, calcitriol, ipriflavone, teriparatide, denosumab, or any medication other than calcium and vitamin D preparations to treat bone mineral density loss.
- Has been a participant in an investigational drug or device study within the 1 month prior to the first screening visit.
Data sourced from ClinicalTrials.gov (NCT03103087). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.