SPIRIT 2: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Endometriosis-Associated Pain
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 623
- 试验地点
- 75
- 主要终点
- Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT)
研究概览
简要总结
The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain.
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, once-daily relugolix (40 mg) co-administered with either 12 or 24 weeks of low-dose E2 (1.0 mg) and NETA (0.5 mg), compared with placebo.
Approximately 600 women with endometriosis-associated pain were enrolled and randomized 1:1:1 to Group A - relugolix plus low-dose hormonal add-back therapy, Group B - relugolix monotherapy for 12 weeks followed by co-administration with low-dose hormonal add-back therapy, or Group C - placebo (N = 200 per group).
Eligible participants were randomized on Baseline Day 1 to Treatment Group A, B, or C, in the double-blind period.
Eligible participants, including those randomized to placebo, were offered the opportunity to enroll in an 80-week open label extension study where participants received 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 participant's last dose of study drug.
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
- •Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing of the informed consent form.
- •Has agreed to use only study-specified analgesic medications during the study and is not known to be intolerant to these.
- •Has a diagnosis of endometriosis and has had, within 10 years prior to signing the informed consent form, surgical or direct visualization and/or histopathologic confirmation of endometriosis, for example, during a laparoscopy or laparotomy.
- •During the Run-In Period (35 to 70 days prior to treatment period) has a dysmenorrhea NRS score ≥ 4.0 on at least 2 days and
- •Mean NMPP NRS score ≥ 2.5, or
- •Mean NMPP NRS score ≥ 1.25 and NMPP NRS score ≥ 5.0 on ≥ 4 days.
排除标准
- •Has a history of chronic pelvic pain that is not caused by endometriosis.
- •Has any chronic pain or frequently recurring pain condition, other than endometriosis that is treated with opioids or requires analgesics for ≥ 7 days per month.
- •Has had surgical procedures for treatment of endometriosis within the 3 months prior to the Screening visit.
- •Has a history of or currently has osteoporosis or other metabolic bone disease.
- •Has a clinically significant gynecologic condition, other than endometriosis, identified during Screening or Run-In period transvaginal ultrasound or endometrial biopsy.
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)
Placebo (Group C)
Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.
干预措施: Relugolix placebo (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)
结局指标
主要结局
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT)
时间窗: Week 24 or EOT
Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary (e-Diary). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
Percentage Of Participants Who Meet The Non-Menstrual Pelvic Pain (NMPP) Responder Criteria At Week 24 Or EOT
时间窗: Week 24 or EOT
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.
次要结局
- Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24(Baseline, Week 24)
- Change From Baseline In Dysmenorrhea NRS Score At Week 24 Or EOT(Baseline, Week 24 or EOT)
- Change From Baseline In NMPP NRS Score At Week 24 Or EOT(Baseline, Week 24 or EOT)
- Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 Or EOT(Baseline, Week 24 or EOT)
- Change From Baseline In Dyspareunia NRS Scores At Week 24 Or EOT(Baseline, Week 24 or EOT)
- Percentage Of Participants Who Are Not Using Opioids For Endometriosis-associated Pain At Week 24 Or EOT(Week 24 or EOT)
- Change From Baseline In Analgesic Use For Endometriosis-associated Pain Based On Mean Pill Count At Week 24 Or EOT(Baseline, Week 24 or EOT)
- Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24(Baseline to Week 24)
- Dysmenorrhea Responder Rate By Month(Baseline to Week 24)
- NMPP Responder Rate By Month(Baseline to Week 24)
- Change In Dysmenorrhea NRS Score By Month(Baseline to Week 24)
- Change In NMPP NRS Score By Month(Baseline to Week 24)
- Change In Overall Pelvic Pain NRS Score By Month(Baseline to Week 24)
- Change From Baseline In PGA For Pain Severity At Week 24(Baseline, Week 24)
- Change In Dyspareunia NRS Score By Month(Baseline to Week 24)
- Change From Baseline In Ibuprofen Use At Week 24 Or EOT(Baseline, Week 24)
- Change From Baseline In Opioid Use At Week 24 Or EOT(Baseline, Week 24)
- Change From Baseline In The Mean Dysmenorrhea Functional Impairment At Week 24 Or EOT(Baseline, Week 24 or EOT)
- Change From Baseline In The Mean NMPP Functional Impairment At Week 24 Or EOT(Baseline, Week 24 or EOT)
- Change From Baseline In The Mean Dyspareunia Functional Impairment At Week 24 Or EOT(Baseline, Week 24 or EOT)
- Change From Baseline In Patient Global Assessment (PGA) For Dysmenorrhea Symptom Severity At Week 24(Baseline, Week 24)
- Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Dysmenorrhea At Week 24(Week 24)
- Change From Baseline In PGA For NMPP Symptom Severity At Week 24(Baseline, Week 24)
- Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For NMPP At Week 24(Week 24)
- Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Pain Severity At Week 24(Week 24)
- Change From Baseline In PGA For Function At Week 24(Baseline, Week 24)
- Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Function At Week 24(Week 24)
- Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 24(Week 24)
- Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 24(Week 24)
- Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 24(Week 24)
- Change From Baseline In The Non-Pain Of The EHP-30 Domains At Week 24(Baseline, Week 24)
- Change From Baseline In The EHP-30 Scale Total Score At Week 24(Baseline, Week 24)
- Change From Baseline In The EHP Work Domain Score At Week 24(Baseline, Week 24)
- Categorical Change From Baseline In Quality Of Life Assessed By European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Questionnaire At Week 24(Baseline, Week 24)
- Change From Baseline To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24(Baseline, Week 24)
- Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA(Week 24 or EOT)
- Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA(Week 24 or EOT)
- Change From Baseline In The EHP-30 Pain Score At Week 24 For Relugolix Plus Delayed E2/NETA(Baseline, Week 24)
- Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 For Relugolix Plus Delayed E2/NETA(Baseline to Week 24)
- Percentage Change From Baseline In Bone Mineral Density At The Lumbar Spine (L1-L4) At Week 12(Baseline, Week 12)
- Percentage Change From Baseline In Bone Mineral Density At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 24(Baseline, Week 24)
- Percentage Of Participants Experiencing Vasomotor Symptoms At Week 12 Between Group A And B(Week 12)
- Change From Baseline In Serum Concentrations Of Luteinizing Hormone, Follicle Stimulating Hormone, Estradiol, And Progesterone(Baseline, Week 24)