A Phase 3b Study to Evaluate the Long-Term Safety of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 478
- 试验地点
- 157
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
This randomized multicenter phase 3b study seeks to evaluate the safety of elagolix in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. This study was double-blind (DB) during the first 12 months and open-label (OL) for the next 36 months.
详细描述
478 participants were randomly assigned at a ratio of 2:1 to the following treatment groups:
- Elagolix 300 mg twice daily (BID) plus estradiol 1.0 mg/norethindrone acetate 0.5 mg (E2/NETA) once daily (QD) for 48 months, followed by 12 months PTFU
- Placebo for 12 months, followed by elagolix 300 mg BID plus E2/NETA QD for 36 months, followed by 12 months PTFU
This study was double-blinded during the first 12 months and open-label for the next 36 months. Participants entered up to 12 months of PTFU after completing treatment Month 48 (or at any time a participant prematurely discontinued treatment).
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
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participant is a premenopausal female at the time of Screening.
- •Participant has a diagnosis of uterine fibroids documented by a Pelvic Ultrasound [Transabdominal ultrasound (TAU) or transvaginal ultrasound (TVU)].
- •Participant has Heavy Menstrual Bleeding (HMB) associated with uterine fibroids as evidenced by Menstrual Blood Loss (MBL) > 80 mL during each of two screening menses as measured by the alkaline hematin method.
- •Participant has negative urine and/or serum pregnancy test during Washout (if applicable) and/or Screening and just prior to first dose.
- •Participant has an adequate endometrial biopsy performed during Screening, the results of which show no clinical significant endometrial pathology.
排除标准
- •Participant has screening pelvic ultrasound or Saline Infusion Sonohysterography (SIS) results that show a clinically significant gynecological disorder.
- •Participant has history of osteoporosis or other metabolic bone disease.
- •Participant has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.
- •Participant has a history of major depression or post-traumatic stress disorder (PTSD) episode within 2 years of screening, OR a history of other major psychiatric disorder at any time (e.g., schizophrenia, bipolar disorder).
- •Participant is using any systemic corticosteroids for over 14 days within 3 months prior to Screening or is likely to require treatment with systemic corticosteroids during the course of the study. Over the counter and prescription topical, inhaled, intranasal or intra-articular injectable (for occasional use) corticosteroids are allowed.
研究组 & 干预措施
Elagolix plus estradiol (E2)/norethindrone acetate (NETA)
干预措施: Elagolix (Drug)
Elagolix plus estradiol (E2)/norethindrone acetate (NETA)
干预措施: Estradiol /norethindrone acetate (E2/NETA) (Drug)
Placebo
干预措施: E2/NETA Placebo (Other)
Placebo
干预措施: Elagolix Placebo (Other)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: Baseline to 60 months
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. AEs during the 12-month DB period were defined as any AEs with onset on/after first dose of study drug during the DB period and no more than 30 days after the last dose of study drug for participants who discontinued early during the DB period, or until the first dose of study drug in the OL period for participants who entered the OL Treatment Period. AEs during the OL period were defined as AEs with onset on/after first dose of study drug during the OL period and no more than 30 days after the last dose of study drug. During the post-treatment follow-up (PTFU) period, adverse events were collected from 30 days post-last dose until end of study. Safety reporting during the PTFU period included AESIs. Other AEs may have also been reported.
次要结局
- Bone Mineral Density (BMD) Recovery After up to 48 Months of Treatment(Baseline through Month 60)