Phase 2a Proof Of Concept Study to Evaluate the Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 271
- 主要终点
- Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
研究概览
简要总结
The purpose of this proof-of-concept study is to assess the safety and effectiveness of elagolix versus placebo to reduce uterine bleeding associated with uterine fibroids, and to reduce fibroid volume and uterine volume in premenopausal women 20 to 49 years of age with heavy uterine bleeding.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Subject is a pre-menopausal female 20 to 49 years of age.
- •Subject has a diagnosis of uterine fibroids documented by a pelvic ultrasound assessed by a central reader and verification that a fibroid present met the following criteria:
- •At least 1 fibroid with diameter ≥ 2 cm (longest diameter), or multiple small fibroids with a total uterine volume of ≥ 200 cm³ to ≤ 2,500 cm³ (approximately 22 weeks' gestation) as documented by a centrally read ultrasound.
- •Only intramural, submucosal non-pedunculated, and subserosal fibroids qualified subjects for enrollment (intracavitary pedunculated fibroids were exclusionary).
- •Ultrasound procedures were performed during the Screening Period, and subjects were not randomized until the investigator reviewed the central reader results verifying the inclusion requirements.
- •Subject has a history of regular menstrual cycles between 24 to 35 days.
- •Subject has heavy uterine bleeding associated with uterine fibroids as evidenced by blood loss > 80 mL during 2 screening menstrual cycles, measured by the alkaline hematin method.
排除标准
- •Subject has had a myomectomy, uterine artery embolization, or high intensity focused ultrasound for fibroid destruction within 1 year prior to randomization or any history of endometrial ablation.
- •Subject has a history of osteoporosis or other metabolic bone disease.
- •Subject shows evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including depression), or neurologic diseases or any uncontrolled medical illness such as uncontrolled type 2 diabetes.
- •Subject has a history of clinically significant condition(s) including but not limited to:
- •Endometriosis
- •Epilepsy or seizures
- •Type 1 diabetes
- •Any cancer (except basal cell carcinoma of the skin), including breast or ovarian cancer or subject has taken any systemic cancer chemotherapy
研究组 & 干预措施
Cohort 1 Elagolix 200 mg BID
Participants received elagolix 200 mg twice a day for 3 months.
干预措施: Elagolix (Drug)
Cohort 4 Elagolix 400 mg QD
Participants received elagolix 400 mg once a day (QD) for 3 months.
干预措施: Elagolix (Drug)
Cohort 4 Elagolix 100 mg BID
Participants received elagolix 100 mg twice a day (BID) for 3 months.
干预措施: Elagolix (Drug)
Cohort 4 Placebo
Participants received placebo to elagolix BID for 3 months.
干预措施: Placebo (Drug)
Cohort 1 Placebo
Participants received placebo to elagolix twice a day for 3 months.
干预措施: Placebo (Drug)
Cohort 3 Elagolix 200 mg BID + LD E2/NETA
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
干预措施: Elagolix (Drug)
Cohort 3 Elagolix 200 mg BID + LD E2/NETA
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
干预措施: Estradiol/Norethindrone acetate (E2/NETA) (Drug)
Cohort 5 Elagolix 600 mg QD
Participants received elagolix 600 mg once a day for 3 months.
干预措施: Elagolix (Drug)
Cohort 2 Elagolix 300 mg BID
Participants received elagolix 300 mg twice a day for 3 months.
干预措施: Elagolix (Drug)
Cohort 2 Placebo
Participants received placebo to elagolix BID for 3 months.
干预措施: Placebo (Drug)
Cohort 6 Elagolix 300 mg BID + CEP
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
干预措施: Elagolix (Drug)
Cohort 6 Elagolix 300 mg BID + CEP
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
干预措施: Estradiol (Drug)
Cohort 6 Elagolix 300 mg BID + CEP
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
干预措施: Progesterone (Drug)
结局指标
主要结局
Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
时间窗: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
次要结局
- Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid(Baseline and month 3)
- Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding(Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90))
- Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3(Month 3 (average bleeding score over days 61 to 90))
- Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment(Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90))
- Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3(Baseline and Month 3)
- Change in Hemoglobin Concentration From Baseline to Month 3(Baseline and Month 3)
- Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)(Baseline and month 3)
- Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores(Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90))
- Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0(Baseline and month 3)
- Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0(Baseline and month 3)
- Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)(Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90))
- Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment(The last 28 days of treatment (approximately days 61 to 90))
- Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment(Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90))
- Change From Baseline to Month 3 in Uterine Bleeding Score(Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90))
- Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit(Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.)
- Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding(Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90))
- Percent Change From Baseline to Month 3 in Uterine Volume(Baseline and month 3)
- Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit(Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.)
- Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment(The last 56 days of treatment (approximately days 33 to 90))