Background This is a placebo-controlled multi-national trial of roluperidone, a compound with antagonist properties for 5-HT2A, sigma2, and α1A-adrenergic receptors, targeting negative symptoms in patients with schizophrenia. This trial follows a previous trial that demonstrated roluperidone superiority over placebo in a similar patient population. Methods Roluperidone 32 mg/day, roluperidone 64 mg/day, or placebo was administered for 12 weeks to 513 patients with schizophrenia with moderate to severe negative symptoms. The primary endpoint was the PANSS-derived Negative Symptom Factor Score (NSFS) and the key secondary endpoint was Personal and Social Performance scale (PSP) total score. Results NSFS scores were lower (improved) for roluperidone 64 mg compared to placebo and marginally missing statistical significance for the intent-to-treat (ITT) analysis data set (P ≤ .064), but reached nominal significance (P ≤ .044) for the modified-ITT (m-ITT) data set. Changes in PSP total score were statistically significantly better on roluperidone 64 mg compared to placebo for both ITT and m-ITT (P ≤ .021 and P ≤ .017, respectively). Conclusions Results of this trial confirm the potential of roluperidone as a treatment of negative symptoms and improving everyday functioning in patients with schizophrenia. Study registration: Eudra-CT: 2017-003333-29; NCT03397134.

中文翻译：

---

罗哌立酮治疗精神分裂症阴性症状的疗效和安全性


背景 这是一项针对罗潘立酮的安慰剂对照跨国试验，罗潘立酮是一种具有 5-HT2A、sigma2 和 α1A 肾上腺素受体拮抗剂特性的化合物，针对精神分裂症患者的阴性症状。该试验是继之前的一项试验之后进行的，该试验证明了罗潘立酮在类似患者群体中优于安慰剂。方法 对 513 名具有中度至重度阴性症状的精神分裂症患者给予罗潘立酮 32 mg/天、罗潘立酮 64 mg/天或安慰剂 12 周。主要终点是 PANSS 衍生的阴性症状因素评分 (NSFS)，关键的次要终点是个人和社会绩效量表 (PSP) 总分。结果 与安慰剂相比，罗卢哌酮 64 mg 的 NSFS 评分较低（改善），意向治疗 (ITT) 分析数据集的统计显着性略有缺失 (P ≤ .064)，但达到了名义显着性 (P ≤ .044)对于修改后的 ITT (m-ITT) 数据集。与安慰剂相比，64 mg 罗潘立酮 ITT 和 m-ITT 的 PSP 总分变化在统计学上显着改善（分别为 P ≤ .021 和 P ≤ .017）。结论 该试验的结果证实了罗潘立酮治疗精神分裂症患者阴性症状和改善日常功能的潜力。研究注册：Eudra-CT：2017-003333-29； NCT03397134。