LIBERTY 1: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Co-Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 388
- 试验地点
- 94
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy and safety study to evaluate 24 weeks of oral daily relugolix 40 mg co-administered with low-dose E2 and NETA (Group A) and 12 weeks of daily oral relugolix 40 mg alone followed by 12 weeks of daily oral relugolix 40 mg co-administered with low-dose E2 and NETA (Group B) compared with 24 weeks of placebo (Group C).
All participants completing the Week 24 visit, including women randomized to placebo, were offered the opportunity to enroll in an open-label extension study in which all eligible participants will receive relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a follow-up visit approximately 30 days after the end of treatment (that is, after the participant's last dose of study medication).
Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and assessments of bone mineral density.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 patient'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.
研究组 & 干预措施
Relugolix plus E2/NETA (Group A)
Relugolix co-administered with E2/NETA for 24 weeks.
干预措施: Relugolix (Drug)
Relugolix plus E2/NETA (Group A)
Relugolix co-administered with E2/NETA for 24 weeks.
干预措施: Estradiol/norethindrone acetate (Drug)
Relugolix plus Delayed E2/NETA (Group B)
Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.
干预措施: Relugolix (Drug)
Relugolix plus Delayed E2/NETA (Group B)
Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.
干预措施: Estradiol/norethindrone acetate (Drug)
Relugolix plus Delayed E2/NETA (Group B)
Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.
干预措施: Estradiol/norethindrone acetate placebo (Drug)
Placebo (Group C)
Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.
干预措施: Estradiol/norethindrone acetate placebo (Drug)
Placebo (Group C)
Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.
干预措施: Relugolix placebo (Drug)
结局指标
主要结局
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
时间窗: From Baseline up to last 35 days of treatment (up to Week 24)
A responder was a participant who had MBL volume of \< 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 24). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 24/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented. As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
次要结局
- Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment(From Baseline up to last 35 days of treatment (up to Week 24))
- Percent Change From Baseline At Week 24 In MBL Volume(Baseline, Week 24)
- Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24(From Baseline up to Week 24)
- Percentage Of Participants With A Maximum NRS Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment(From Baseline up to Week 24)
- Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume(Baseline, Week 24)
- Percent Change From Baseline At Week 24 In Uterine Volume(Baseline, Week 24)
- Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)(Baseline, Week 24)
- Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 To L4), As Assessed By DXA(Baseline, Week 12)
- Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck(Baseline, Week 24)
- Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12(Baseline through Week 12)
- Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24(Baseline through Week 24)
- Predose Trough Concentrations Of Relugolix And Norethindrone (NET) In The Relugolix Plus E2/NETA Group At Week 24(Week 24)
- Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24(Week 24)
- Change From Baseline At Week 24 In Predose Concentrations Of Estradiol In The Relugolix Plus E2/NETA Group(Baseline, Week 24)
- Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire(Baseline, Week 24)
- Participants Achieving Improvement From Baseline In The PGA Questionnaire For Uterine Fibroid-related Function From Baseline At Week 24(From Baseline through Week 24)
- Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities(Baseline, Week 24)
- Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities(Baseline, Week 24)
- Number Of Participants Who Achieved A Maximum NRS Score ≤ 1 For Uterine Fibroid-associated Pain Over The Last 35 Days Of Treatment Who Had Maximum Pain Scores ≥ 4 During The 35 Days Prior To Randomization(From Baseline up to the last 35 days of treatment (up to 24 weeks))
- Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline(Baseline, Week 24)
- Time To MBL Response(From Baseline through Week 24)
- Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20(Baseline, Week 24)
- Participants Achieving Improvement From Baseline In The PGA Questionnaire For Symptoms From Baseline At Week 24(From Baseline through Week 24)
- Sustained Amenorrhea Rate (No Or Negligible Bleeding)(Week 24)
- Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)(From Baseline through Week 24)
- Time To Achieving Amenorrhea (No Or Negligible Bleeding)(From Baseline through Week 24)
- Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24(From Baseline through Week 24)
- Percent Change From Baseline In Hemoglobin For Women With a Hemoglobin ≤ 10.5 g/dL At Baseline(Week 24)
- Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal(Week 24)
- Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score(Baseline, Week 24)
- Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score(Baseline, Week 24)
- Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score(Baseline, Week 24)
- Change From Baseline In UFS-QoL Score By Health-Related Quality Of Life Total Score(Baseline, Week 24)
- Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score(From Baseline through Week 24)
- Change From Baseline In UFS-QoL Bleeding And Pelvic Discomfort Scale Score(Baseline, Week 24)
- Change From Baseline In Luteinizing Serum Concentration At Week 24(Baseline, Week 24)
- Change From Baseline In Follicle Stimulating Serum Concentration At Week 24(Baseline, Week 24)
- Change From Baseline In E2 Serum Concentration At Week 24(Baseline, Week 24)
- Change From Baseline In Progesterone Serum Concentration At Week 24(Baseline, Week 24)
- Number Of Responders With At Least 20 Points Decrease In UFS-QoL Bleeding And Pelvic Discomfort Scale Score(Baseline, Week 24)
- Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11(Baseline, Week 24)
- Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire(Baseline, Week 24)
- Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29(Baseline, Week 24)