A Study to Evaluate Safety and Efficacy of Elagolix Alone or Elagolix With Hormonal Add-Back in Subjects With Endometriosis With Associated Moderate to Severe Pain
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 37
- 主要终点
- Proportion of Responders at Month 6 Based on NMPP Pain Scale
研究概览
简要总结
This is a Phase 3, dose-escalation study designed to evaluate the safety and efficacy of both elagolix alone and elagolix plus estradiol/norethindrone acetate (E2/NETA) over 24 months in the management of endometriosis with associated moderate to severe pain in premenopausal women.
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
- •Participant is a premenopausal female 18 to 49 years of age (inclusive) at the time of Screening.
- •Participant has a documented surgical diagnosis (e.g., laparoscopy or laparotomy) of endometriosis established by visualization or histology within 10 years prior to entry into Washout or Screening,
- •Participant must agree to use only those rescue analgesics permitted by the protocol during the Screening and Treatment Periods for her endometriosis-associated pain.
- •Participant must have the following documented in the e-Diary during the last 35 days prior to Study Day 1:
- •At least 2 days of "moderate" or "severe" DYS, AND either,
- •At least 2 days of "moderate" or "severe" NMPP and an average NMPP score of at least 1.0, OR
- •At least 4 days of "moderate" or "severe" NMPP and an average NMPP score of at least 0.5.
排除标准
- •Participant has chronic pelvic pain that is not caused by endometriosis that requires chronic analgesic therapy, which would interfere with the assessment of endometriosis-associated pain.
- •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 or intranasal corticosteroids are allowed.
- •Participant has a history of major depression or post-traumatic stress disorder (PTSD) within 2 years prior to screening or other major psychiatric disorder at any time
- •Participant has a history of suicide attempts or answered "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or prior to study drug dosing on Day
- •Participant has any condition that would interfere with obtaining adequate dual energy x-ray absorptiometry (DXA) measurements
- •Screening DXA results of the lumbar spine (L1 - L4), femoral neck or total hip bone mineral density (BMD) corresponding to less than 2 or more standard deviations below normal (Z-score < -2.0 for participants < 40 years of age, T-score for participants >= 40 years of age).
- •Participant has either
- •a newly diagnosed, clinically significant medical condition that requires therapeutic intervention (e.g., new onset hypertension) that has not been stabilized 30 days prior to enrollment on Day 1 OR
- •a clinically significant medical condition that is anticipated to required intervention during the course of study participation (e.g., anticipated major elective surgery) OR
- •an unstable medical condition that makes the participant an unsuitable candidate for the study in the opinion of the Investigator
- •Participant has any conditions contraindicated with use of E2/NETA
研究组 & 干预措施
Arm A
Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD
Month 4 Through Month 24 (Double-Blind): Efficacy responders to elagolix 150 mg QD at Month 3 and continue treatment through Month 24
干预措施: elagolix (Drug)
Arm C
Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD
Month 4 Through Month 24 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group and continue treatment through Month 24.
干预措施: elagolix (Drug)
Arm C
Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD
Month 4 Through Month 24 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group and continue treatment through Month 24.
干预措施: estradiol/norethindrone acetate (E2/NETA) (Drug)
Arm D
Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD
Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 150 mg QD treatment group
Month 7 Through Month 24 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 6 and assigned to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group and continue treatment through Month 24.
干预措施: elagolix (Drug)
Arm D
Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD
Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 150 mg QD treatment group
Month 7 Through Month 24 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 6 and assigned to elagolix 200 mg BID plus E2/NETA 1/0.5 mg QD treatment group and continue treatment through Month 24.
干预措施: estradiol/norethindrone acetate (E2/NETA) (Drug)
Arm B
Day 1 Through Month 3 (Open-Label): Open-Label elagolix 150 mg QD
Month 4 Through Month 6 (Double-Blind): Incomplete efficacy responders to elagolix 150 mg QD at Month 3 and randomized to elagolix 150 mg QD treatment group
Month 7 Through Month 24 (Double-Blind): Efficacy responders to elagolix 150 mg QD at Month 6 and continue treatment through Month 24.
干预措施: elagolix (Drug)
结局指标
主要结局
Proportion of Responders at Month 6 Based on NMPP Pain Scale
时间窗: Month 6
Proportion of responders at Month 6 based upon the scale for NMPP pain scale (ranging from 0 \[none\] to 3 \[severe\]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.
Proportion of Responders at Month 6 Based on DYS Pain Scale
时间窗: Month 6
Proportion of responders at Month 6 based upon the scale for DYS pain scale (ranging from 0 \[none\] to 3 \[severe\]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.
次要结局
- Change From Baseline in DYS at Month 6(Month 0 (baseline), Month 6)
- Change From Baseline in NMPP at Month 6(Month 0 (baseline), Month 6)
- Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Scores Over Time: Percent Work Missed Due to Problem(Month 0 (baseline), Month 6)
- WPAI:SHP Scores Over Time: Percent Impairment While Working Due to Problem(Month 0 (baseline), Month 6)
- Change From Baseline in Daily Diary Endometriosis-Associated Pain Score Via Numeric Rating Scale (NRS) at Month 6(Month 0 (baseline), Month 6)
- Change From Baseline in Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) at Month 6(Month 0 (baseline), Month 6)
- Percentage of Participants With 30% or More Reduction From Baseline Based on the 35 Day Mean of the Daily Diary Endometriosis-Associated Pain Score Via NRS at Month 6(Month 6)
- Proportion of Responders Over Time(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Proportion of Responders Over Time (Not Taking Into Consideration of Analgesic Use)(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Change From Baseline Over Time in Monthly Average DYS Pain Score(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Change From Baseline Over Time in Monthly Average NMPP Pain Score(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Change From Baseline in Dyspareunia at Month 6(Month 0 (baseline), Month 6)
- Percent Change From Baseline to Each Month During the Treatment Period for DYS(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Percent Change From Baseline to Each Month During the Treatment Period for NMPP(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Number of Analgesic Use Responders and Non-Responders Over Time(Months 1, 2, 3, 4, 5, 6)
- Patient Global Impression of Change (PGIC) Scores Over Time(Months 1, 2, 3, 4, 5, 6)
- Overall Endometriosis-Associated Pain Via NRS (7-Day Recall) Scores Over Time(Month 0 (baseline), Months 1, 2, 3, 4, 5, 6)
- Endometriosis Health Profile-30 (EHP-30) Scores Over Time: Pain(Month 0 (baseline), Months 3, 6)
- EHP-30 Scores Over Time: Control and Powerlessness(Month 0 (baseline), Months 3, 6)
- EHP-30 Scores Over Time: Self-Image(Month 0 (baseline), Months 3, 6)
- EHP-30 Scores Over Time: Sexual Intercourse(Month 0 (baseline), Months 3, 6)
- EuroQol-5D 5 Level (EQ-5D-5L) Scores Over Time: Mobility(Month 0 (baseline), Months 3, 6)
- EQ-5D-5L Scores Over Time: Self-Care(Month 0 (baseline), Months 3, 6)
- PROMIS Fatigue Short Form 6a Scores Over Time(Month 0 (baseline), Month 6)
- EQ-5D-5L Scores Over Time: Usual Activities(Month 0 (baseline), Months 3, 6)
- EQ-5D-5L Scores Over Time: Pain/Discomfort(Month 0 (baseline), Months 3, 6)
- EQ-5D-5L Scores Over Time: Anxiety/Depression(Month 0 (baseline), Months 3, 6)
- EQ-5D-5L VAS Scores Over Time: Health Today(Month 0 (baseline), Months 3, 6)
- EHP-30 Scores Over Time: Emotional Well-Being(Month 0 (baseline), Months 3, 6)
- EHP-30 Scores Over Time: Social Support(Month 0 (baseline), Months 3, 6)
- WPAI:SHP Scores Over Time: Percent Overall Work Impairment Due to Problem(Month 0 (baseline), Month 6)
- WPAI:SHP Scores Over Time: Percent Activity Impairment Due to Problem(Month 0 (baseline), Month 6)
- Health Endometriosis Treatment Satisfaction Questionnaire (ETSQ) Scores Over Time(Month 0 (baseline), Months 3, 6)