Anand Ravi, Turolla Alessio, Chinellato Giovanni, Sansi Francesca, Roy Arjun, Hartman Richard
Anand Pharma Consulting (APC), St. Moritz, Switzerland.
Newron Pharmaceuticals SpA, Bresso, Italy.
Neuropharmacology. 2025 Mar 15;266:110275. doi: 10.1016/j.neuropharm.2024.110275. Epub 2024 Dec 19.
Evenamide, a glutamate modulator, is currently in phase 3 of development as add-on treatment to antipsychotics in patients with inadequate response or treatment-resistant schizophrenia. This study was designed to determine if patients with chronic schizophrenia inadequately responding to a second-generation antipsychotic would benefit from add-on treatment with evenamide at a dose of 30 mg bid.
Study 008A was a prospective, 4-week, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of oral doses of evenamide of 30 mg bid in patients with chronic schizophrenia treated at stable therapeutic doses of a second-generation antipsychotic. Outpatients aged ≥18 years, both males and females, with a diagnosis of schizophrenia (DSM-V), who had been receiving antipsychotics for at least 2 years at stable doses, but still symptomatic (PANSS 70-85, CGI-S 4-6, predominant positive symptoms), were eligible for the study. Patients were randomised equally to evenamide 30 mg or placebo, given bid, after completing a 21-day screening period. The primary outcome (change from baseline in PANSS total score) was assessed weekly, with the primary endpoint at 4 weeks.
A total of 291 patients were enrolled, of which 11 (3·8%) discontinued prematurely, overall. Add-on treatment with evenamide was associated to a statistically significant (the absolute difference of the two treatment groups for the PANSS Total at Day 29, primary efficacy endpoint, was = 2·5 [p-value<0.05] that is associated with a Cohen's d effect size = 0·33) and clinically meaningful benefit compared to placebo across all efficacy measures, and was well tolerated.
The demonstration of statistically significant and clinically meaningful benefit of evenamide, a glutamate modulator, as add-on treatment in patients with chronic schizophrenia inadequately responding to their second-generation antipsychotic may represent a new treatment paradigm for this population.
依维酰胺是一种谷氨酸调节剂，目前正处于作为抗精神病药物的附加治疗用于对治疗反应不足或难治性精神分裂症患者的3期开发阶段。本研究旨在确定对第二代抗精神病药物反应不足的慢性精神分裂症患者是否能从每日两次、剂量为30毫克的依维酰胺附加治疗中获益。
研究008A是一项前瞻性、为期4周的随机、双盲、安慰剂对照研究，评估在接受第二代抗精神病药物稳定治疗剂量的慢性精神分裂症患者中，每日两次口服30毫克依维酰胺的安全性、耐受性和疗效。年龄≥18岁、诊断为精神分裂症（DSM-V）、已接受抗精神病药物稳定剂量治疗至少2年但仍有症状（阳性和阴性症状量表总分70 - 85分、临床总体印象量表严重程度4 - 6分、以阳性症状为主）的门诊患者符合研究条件。在完成21天的筛查期后，患者被等分为依维酰胺30毫克组或安慰剂组，每日两次给药。每周评估主要结局（阳性和阴性症状量表总分相对于基线的变化），主要终点为4周时的情况。
总共招募了291名患者，其中11名（3.8%）提前退出研究。总体而言，与安慰剂相比，依维酰胺附加治疗在所有疗效指标上均具有统计学显著意义（在第29天主要疗效终点时，两个治疗组在阳性和阴性症状量表总分上的绝对差异为2.5[p值<0.05]，对应科恩d效应量为0.33）且具有临床意义的益处，并且耐受性良好。
谷氨酸调节剂依维酰胺作为附加治疗用于对第二代抗精神病药物反应不足的慢性精神分裂症患者，显示出统计学显著和临床意义的益处，这可能代表了该人群的一种新治疗模式。
