Research and Development, Bayer AG, Berlin, Germany.
Pharmacovigilance, Bayer AG, Berlin, Germany.
BMC Womens Health. 2024 Jun 19;24(1):353. doi: 10.1186/s12905-024-03188-8.
The SCHUMANN study evaluated the efficacy and safety of the selective P2 × 3 antagonist eliapixant in patients with endometriosis-associated pelvic pain (EAPP).
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).
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.
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.
ClinicalTrials.gov identifier NCT04614246; registered November 3, 2020.
SCHUMANN 研究评估了选择性 P2×3 拮抗剂 eliapixant 治疗子宫内膜异位症相关盆腔疼痛（EAPP）患者的疗效和安全性。
SCHUMANN 是一项随机、安慰剂和活性对照、双盲安慰剂和开放标签比较、平行组、多中心、剂量发现 2b 期研究。参与者为经手术诊断为子宫内膜异位症且符合 EAPP 标准的女性。参与者按 1:1:1:1 随机分为每日 2 次（BID）25mg、75mg 或 150mg 口服 eliapixant 或安慰剂，治疗 12 周。还包括了探索性每日一次 elagolix 150mg 治疗组。主要终点是从基线到干预结束（EOI）时平均最差 EAPP 的绝对变化。
共有 215 名参与者被随机分配接受治疗（44 名接受 eliapixant 25mg、44 名接受 eliapixant 75mg、43 名接受 eliapixant 150mg、43 名接受安慰剂、41 名接受 elagolix 150mg）。由于安全原因，该研究提前终止；治疗和入组立即停止，完成人数不到计划的 50%。研究发现，各组之间 EAPP 缓解从基线无显著差异，无显著剂量反应模型。elagolix 150mg 组的疼痛缓解优于其他任何组。与 eliapixant 先前已知的安全性概况相比，未观察到新的安全性信号，一般耐受性良好。然而，一名接受 eliapixant 150mg BID 的参与者出现中度且可能与药物相关的肝损伤，支持 eliapixant 与肝功能值潜在升高之间的关联，该值在 2 期计划开始前定义。
本研究未达到主要目标，因为从基线到 EAPP 的平均最差变化在治疗组之间未观察到统计学显著或临床相关差异。单次观察到的 1 例中度、可能与药物相关的肝损伤是在随后的以下适应症中进行的 eliapixant 2 期研究中观察到的第 2 例：难治性或不明原因的慢性咳嗽、糖尿病性神经痛、膀胱过度活动症和 EAPP。因此，研究的获益风险比不再被认为是积极的。
ClinicalTrials.gov 标识符 NCT04614246；2020 年 11 月 3 日注册。
