背景:SCHUMANN研究评估了选择性P2×3拮抗剂在子宫内膜异位症相关性盆腔疼痛(EAPP)患者中的疗效和安全性。
方法:SCHUMANN是随机的,安慰剂和有源比较器控制,安慰剂双盲,对比者开放标签,平行组,多中心,剂量发现2b期研究。参与者是手术诊断为子宫内膜异位症的女性,符合定义的EAPP标准。参与者被随机分为1:1:1:1至每天两次(BID)25毫克,75毫克,或150毫克口服elapixant或安慰剂12周。还包括探索性每日一次elagolix150mg治疗组。主要终点是从基线到干预结束(EOI)的平均最差EAPP的绝对变化。
结果:总体而言,215名参与者被随机分配接受治疗(44至eliapixant25mg,44到eliapixant75毫克,43到eliapixant150毫克,43服用安慰剂,和41到elagolix150毫克)。出于安全原因,研究提前终止;治疗和纳入均立即停止,生产不到计划完成数量的50%。该研究发现各组之间EAPP相对于基线的减少没有显着差异,并且没有明显的剂量反应模型。elagolix150mg组的疼痛减轻效果优于其他组。没有观察到新的安全信号,相对于以前已知的elapixant的安全性,一般耐受性良好。然而,在接受eliapixant150mgBID的参与者中,有一例中度且可能是药物引起的肝损伤,支持eliapixant与肝功能值潜在增加之间的关联。在第2阶段程序开始之前定义。
结论:该研究未达到其主要目标,因为在治疗组之间观察到平均最差EAPP相对于基线的变化无统计学意义或临床相关差异。单个观察到的中度病例,在以下适应症中进行的elapixant2期计划中,可能是药物引起的肝损伤:难治性或无法解释的慢性咳嗽,糖尿病性神经性疼痛,膀胱过度活动症,和EAPP。由于这个原因,研究的获益-风险比不再被认为是正的.
背景:ClinicalTrials.gov标识符NCT04614246;注册于2020年11月3日。
BACKGROUND: The SCHUMANN study evaluated the efficacy and safety of the selective P2 × 3 antagonist eliapixant in patients with endometriosis-associated pelvic pain (EAPP).
METHODS: SCHUMANN was a randomized, placebo- and active comparator-controlled, double-blind to placebo and open-label to comparator, parallel-group, multicenter, dose-finding phase 2b study. The participants were women with surgically diagnosed endometriosis who fulfilled defined EAPP criteria. Participants were randomized 1:1:1:1 to twice daily (BID) 25 mg, 75 mg, or 150 mg oral eliapixant or a placebo for 12 weeks. An exploratory once-daily elagolix 150 mg treatment group was also included. The primary endpoint was the absolute change in mean worst EAPP from baseline to the end of intervention (EOI).
RESULTS: Overall, 215 participants were randomized for treatment (44 to eliapixant 25 mg, 44 to eliapixant 75 mg, 43 to eliapixant 150 mg, 43 to a placebo, and 41 to elagolix 150 mg). For safety reasons, the study was terminated early; both treatment and enrollment stopped immediately, producing less than 50% of the planned number of completers. The study found no significant differences in EAPP reduction from baseline between groups and no significant dose-response model. The elagolix 150 mg group showed better pain reduction than any of the other groups. No new safety signals were observed, relative to the previously known safety profile of eliapixant, which was generally well tolerated. However, one case of moderate and probably drug-induced liver injury in a participant receiving eliapixant 150 mg BID supported the association between eliapixant and a potential increase in liver function values, defined before the start of the phase 2 program.
CONCLUSIONS: This study did not meet its primary objective as no statistically significant or clinically relevant differences in changes of mean worst EAPP from baseline were observed between treatment groups. The single observed case of moderate, probably drug-induced liver injury was the second case in the eliapixant phase 2 program conducted in the following indications: refractory or unexplained chronic cough, diabetic neuropathic pain, overactive bladder, and EAPP. Due to this, the benefit-risk ratio for the study was no longer considered to be positive.
BACKGROUND: ClinicalTrials.gov identifier NCT04614246; registered November 3, 2020.