A Phase II, Randomized, Double-blind, Active-controlled Study to Assess the Safety and Efficacy of NBI-56418 in Subjects With Endometriosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 252
- 主要终点
- Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24
研究概览
简要总结
This study is designed to assess the effects of elagolix versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC; also known as depo-provera) on bone mineral density (BMD) during treatment for 24 weeks with a subsequent 24-week post-treatment period.
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 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Be female, aged 18 to 49 years, inclusive
- •Have a total CPSSS of ≥ 6 at screening and baseline (Day 1) in the following categories: dysmenorrhea, dyspareunia, nonmenstrual pelvic pain, pelvic tenderness and induration. The total score must include a total of at least 2 in each of the categories of dysmenorrhea and nonmenstrual pelvic pain.
- •Have had a diagnosis of endometriosis made following laparoscopic visualization of the disease within 8 years of the start of screening with recurrent or persistent symptoms.
- •Have documented negative mammogram results within 12 months of screening if over the age of 40 years.
- •Have menstrual cycles (28 days ±5 days). Assessment of cycle duration should be based on observations in the absence of drugs or conditions that are known to affect the cycle (e.g., oral contraceptives, leuprolide, pregnancy).
- •Have a Body Mass Index (BMI) between 18 and 36 kg/m², inclusive.
- •Agree to use two forms of nonhormonal contraception (e.g. condom with spermicide) during the study.
排除标准
- •Are currently receiving gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, danazol, or have received any of these agents within 6 months of the start of screening.
- •Are currently receiving subcutaneous medroxyprogesterone acetate (DMPA-SC) or intramuscular medroxyprogesterone acetate (DMPA-IM) or have received any of these agents within 3 months of the start of screening.
- •Have been nonresponsive to GnRH agonist or antagonist therapy for the management of endometriosis.
- •Are currently using hormonal contraception or other forms of hormonal therapy or received such treatment within 1 month of the start of screening.
- •Have had surgical treatment for endometriosis (laparoscopy) within 1 month of the start of screening.
- •Have had a hysterectomy or bilateral oophorectomy.
- •Have had prior treatment with NBI-
- •Have uterine fibroids or other pelvic lesions ≥ 5 cm in diameter
- •Have any of the following abnormal cervical smear results at screening (based on the 2001 Bethesda System):
- •Benign endometrial cells (BEC) present, provided subject has irregular uterine bleeding or is over 40 years old
- •Atypical squamous cells of undetermined significance (ASC-US) present, and human papilloma virus (HPV) reflex testing is positive for high risk types or the testing outcome is unknown
- •Atypical squamous cells present, and high-grade squamous intraepithelial lesion (ASC-H) cannot be excluded
- •Atypical glandular cells of uncertain significance (AGUS/AGC): not otherwise specified (NOS), favor neoplasia (FN), favor endocervical, or favor endometrial origin types
- •Low-grade squamous intraepithelial lesion (LSIL) present
- •High-grade squamous intraepithelial lesion (HSIL) present
- •Adenocarcinoma in situ (AIS) / malignant cells present
- •Have BMD with either lumbar spine or femur T-scores below -1.5 at screening as determined by the central DXA facility or have history of pathologic or compression fractures.
- •Have been pregnant within 6 months of screening or currently breast feeding
- •Are using systemic steroids on a chronic or regular basis within 3 months
- •Have unstable medical condition or chronic disease
- •Have chronic pelvic pain that is not caused by endometriosis
研究组 & 干预措施
Elagolix 75 mg BID
Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.
干预措施: Elagolix (Drug)
Elagolix 75 mg BID
Participants received elagolix 75 mg orally twice a day (BID) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.
干预措施: Placebo to DMPA-SC (Drug)
Elagolix 150 mg QD
Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.
干预措施: Elagolix (Drug)
Elagolix 150 mg QD
Participants received elagolix 150 mg orally once a day (QD) for 24 weeks and placebo to DMPA-SC by subcutaneous injection at weeks 1 and 12.
干预措施: Placebo to DMPA-SC (Drug)
DMPA-SC
Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
干预措施: Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) (Drug)
DMPA-SC
Participants received placebo to elagolix orally once a day for 24 weeks and DMPA-SC 104 mg by subcutaneous injection at weeks 1 and 12.
干预措施: Placebo to Elagolix (Drug)
结局指标
主要结局
Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24
时间窗: Baseline and week 24
Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in spine and femur BMD at week 24 was assessed using a one-way analysis of variance (ANOVA) model. The absence of significant bone loss was supported if the lower bounds of the confidence intervals for the mean percent change in BMD were ≥ -2.2% for both the spine and femur at week 24.
Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24
时间窗: Baseline and week 24
Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA). The percent change from baseline in spine and femur BMD at week 24 was assessed using a one-way analysis of variance (ANOVA) model. The absence of significant bone loss was supported if the lower bounds of the confidence intervals for the mean percent change in BMD were ≥ -2.2% for both the spine and femur at week 24.
次要结局
- Percent Change From Baseline in Bone Mineral Density of the Spine at Weeks 12 and 48(Baseline and weeks 12 and 48)
- Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS at Week 24(Baseline and week 24)
- Percentage of Participants With a Response in the Non-menstrual Pelvic Pain Component of the CPSSS Over Time(Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48)
- Change From Baseline in Total CPSSS Excluding Dyspareunia During the Treatment Period(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in Dyspareunia Component of the CPSSS During the Treatment Period(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in Non-menstrual Pelvic Pain Component of the CPSSS During the Treatment Period(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Percent Change From Baseline in Bone Mineral Density of the Femur at Weeks 12 and 48(Baseline and weeks 12 and 48)
- Change From Baseline in N-telopeptide at Weeks 12, 24 and 48(Baseline and weeks 12, 24 and 48)
- Percentage of Participants With a Response in the Dysmenorrhea Component of the Composite Pelvic Signs and Symptoms Score (CPSSS) at Week 24(Baseline and week 24)
- Percentage of Participants With a Response in the Dysmenorrhea Component of the CPSSS Over Time(Baseline and weeks 4, 8, 12, 16, 20, 24, 28, 36, and 48)
- Change From Baseline in Total CPSSS During the Treatment Period(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in Dysmenorrhea Component of the CPSSS During the Treatment Period(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in Pelvic Tenderness Component of the CPSSS During the Treatment Period(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in Pelvic Induration Component of the CPSSS During the Treatment Period(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in in Monthly Peak Visual Analog Scale (VAS) for Pelvic Pain(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in in Monthly Mean Visual Analog Scale (VAS) for Pelvic Pain(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in EHP-5 Control and Powerlessness Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in Endometriosis Health Profile-5 (EHP-5) Pain Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Percentage of Participants Using Analgesics During the Treatment Phase(24 weeks)
- Change From Baseline in EHP-5 Emotional Well-being Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in EHP-5 Social Support Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in EHP-5 Self Image Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in EHP-5 Work Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in EHP-5 Relationship With Children Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in EHP-5 Intercourse Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in EHP-5 Medical Profession Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in EHP-5 Treatment Dimension(Baseline and weeks 4, 8, 12, 16, 20, and 24)