Paul P Yeung, Alan Breier, Haiyuan Zhu, Inder Kaul, Ronald N Marcus
{"title":"Xanomeline和Trospium Chloride用于治疗与精神分裂症相关的躁动：来自3个随机、双盲、安慰剂对照的紧急试验的panss兴奋成分结果。","authors":"Paul P Yeung, Alan Breier, Haiyuan Zhu, Inder Kaul, Ronald N Marcus","doi":"10.4088/JCP.24m15668","DOIUrl":null,"url":null,"abstract":"<p><p><b>Objective:</b> To further characterize the efficacy of oral xanomeline and trospium chloride in the treatment of agitation associated with schizophrenia.</p><p><p><b>Methods:</b> Analyses were performed on the change from baseline of the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC; composed of excitement, tension, hostility, uncooperativeness, and poor impulse control items) data from the 5-week, randomized, double-blind, placebo controlled, inpatient EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials of xanomeline/trospium in adults with schizophrenia with a recent worsening of psychosis requiring hospitalization. The 3 trials met the primary endpoint of reduction from baseline to week 5 in PANSS total score. Data were analyzed from individual studies and were also pooled.</p><p><p><b>Results:</b> The population comprised 640 participants from the pivotal trials which were conducted from September 2018 to December 2022. PANSS-EC scores were significantly reduced with xanomeline/trospium vs placebo at week 5 across all 3 EMERGENT trials. In EMERGENT-1, xanomeline/trospium (n = 83) was statistically significantly superior (Cohen's <i>d</i> =0.62, <i>P</i> = .0002) to placebo (n = 87) in improvement (decrease) of PANSS-EC score at week 5. In EMERGENT-2, xanomeline/trospium (n = 117) was significantly superior (<i>d</i> = 0.43, <i>P</i> = .0026) to placebo (n = 119) at week 5. In EMERGENT-3, xanomeline/ trospium (n = 114) was significantly superior (<i>d</i> = 0.62, <i>P</i> < .0001) to placebo (n = 120) at week 5. Pooled results were consistent with the individual trials.</p><p><p><b>Conclusion:</b> Xanomeline/trospium showed improvement in agitation as measured by PANSS-EC in participants with acute exacerbations of schizophrenia. Xanomeline/trospium is the first in a new class of treatments for schizophrenia based on muscarinic receptor agonism.</p><p><p><b>Trial Registration:</b> ClinicalTrials.gov identifiers: NCT03697252, NCT04659161, NCT04738123.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Xanomeline and Trospium Chloride for the Treatment of Agitation Associated With Schizophrenia: PANSS-Excited Component Results From 3 Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials.\",\"authors\":\"Paul P Yeung, Alan Breier, Haiyuan Zhu, Inder Kaul, Ronald N Marcus\",\"doi\":\"10.4088/JCP.24m15668\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Objective:</b> To further characterize the efficacy of oral xanomeline and trospium chloride in the treatment of agitation associated with schizophrenia.</p><p><p><b>Methods:</b> Analyses were performed on the change from baseline of the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC; composed of excitement, tension, hostility, uncooperativeness, and poor impulse control items) data from the 5-week, randomized, double-blind, placebo controlled, inpatient EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials of xanomeline/trospium in adults with schizophrenia with a recent worsening of psychosis requiring hospitalization. The 3 trials met the primary endpoint of reduction from baseline to week 5 in PANSS total score. Data were analyzed from individual studies and were also pooled.</p><p><p><b>Results:</b> The population comprised 640 participants from the pivotal trials which were conducted from September 2018 to December 2022. PANSS-EC scores were significantly reduced with xanomeline/trospium vs placebo at week 5 across all 3 EMERGENT trials. In EMERGENT-1, xanomeline/trospium (n = 83) was statistically significantly superior (Cohen's <i>d</i> =0.62, <i>P</i> = .0002) to placebo (n = 87) in improvement (decrease) of PANSS-EC score at week 5. In EMERGENT-2, xanomeline/trospium (n = 117) was significantly superior (<i>d</i> = 0.43, <i>P</i> = .0026) to placebo (n = 119) at week 5. In EMERGENT-3, xanomeline/ trospium (n = 114) was significantly superior (<i>d</i> = 0.62, <i>P</i> < .0001) to placebo (n = 120) at week 5. Pooled results were consistent with the individual trials.</p><p><p><b>Conclusion:</b> Xanomeline/trospium showed improvement in agitation as measured by PANSS-EC in participants with acute exacerbations of schizophrenia. Xanomeline/trospium is the first in a new class of treatments for schizophrenia based on muscarinic receptor agonism.</p><p><p><b>Trial Registration:</b> ClinicalTrials.gov identifiers: NCT03697252, NCT04659161, NCT04738123.</p>\",\"PeriodicalId\":50234,\"journal\":{\"name\":\"Journal of Clinical Psychiatry\",\"volume\":\"86 2\",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-03-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4088/JCP.24m15668\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4088/JCP.24m15668","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0
摘要
目的：进一步评价口服异诺米林和氯曲索铵治疗精神分裂症伴动的疗效。方法：分析阳性和阴性综合征量表兴奋成分（PANSS-EC）与基线的变化；由兴奋、紧张、敌意、不合作和冲动控制不良项目组成)数据来自5周的随机、双盲、安慰剂对照、住院患者急诊-1、急诊-2和急诊-3试验的xanomeline/trospium对近期精神病恶化需要住院治疗的成人精神分裂症患者。这3项试验均达到了PANSS总分从基线到第5周下降的主要终点。数据从个别研究中进行分析，也进行汇总。结果：该人群包括640名来自2018年9月至2022年12月进行的关键试验的参与者。在所有3个EMERGENT试验中，在第5周，xanomeline/trospium与安慰剂相比，PANSS-EC评分显著降低。在emergency -1中，xanomeline/trospium （n = 83）在第5周PANSS-EC评分的改善（降低）方面显著优于安慰剂（n = 87） （Cohen’s d =0.62, P = 0.0002）。在emergency -2中，第5周时，xanomeline/trospium （n = 117）显著优于安慰剂（n = 119） （d = 0.43, P = 0.0026）。在emergency -3中，第5周时，xanomeline/ trospium （n = 114）显著优于安慰剂（n = 120） （d = 0.62, P < 0.0001）。汇总结果与单项试验一致。结论：通过PANSS-EC测试，Xanomeline/trospium可以改善精神分裂症急性发作患者的躁动。Xanomeline/trospium是基于毒蕈碱受体激动作用治疗精神分裂症的第一类新药物。试验注册：ClinicalTrials.gov标识符：NCT03697252， NCT04659161, NCT04738123。
Xanomeline and Trospium Chloride for the Treatment of Agitation Associated With Schizophrenia: PANSS-Excited Component Results From 3 Randomized, Double-Blind, Placebo-Controlled EMERGENT Trials.
Objective: To further characterize the efficacy of oral xanomeline and trospium chloride in the treatment of agitation associated with schizophrenia.
Methods: Analyses were performed on the change from baseline of the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC; composed of excitement, tension, hostility, uncooperativeness, and poor impulse control items) data from the 5-week, randomized, double-blind, placebo controlled, inpatient EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials of xanomeline/trospium in adults with schizophrenia with a recent worsening of psychosis requiring hospitalization. The 3 trials met the primary endpoint of reduction from baseline to week 5 in PANSS total score. Data were analyzed from individual studies and were also pooled.
Results: The population comprised 640 participants from the pivotal trials which were conducted from September 2018 to December 2022. PANSS-EC scores were significantly reduced with xanomeline/trospium vs placebo at week 5 across all 3 EMERGENT trials. In EMERGENT-1, xanomeline/trospium (n = 83) was statistically significantly superior (Cohen's d =0.62, P = .0002) to placebo (n = 87) in improvement (decrease) of PANSS-EC score at week 5. In EMERGENT-2, xanomeline/trospium (n = 117) was significantly superior (d = 0.43, P = .0026) to placebo (n = 119) at week 5. In EMERGENT-3, xanomeline/ trospium (n = 114) was significantly superior (d = 0.62, P < .0001) to placebo (n = 120) at week 5. Pooled results were consistent with the individual trials.
Conclusion: Xanomeline/trospium showed improvement in agitation as measured by PANSS-EC in participants with acute exacerbations of schizophrenia. Xanomeline/trospium is the first in a new class of treatments for schizophrenia based on muscarinic receptor agonism.
期刊介绍：
For over 75 years, The Journal of Clinical Psychiatry has been a leading source of peer-reviewed articles offering the latest information on mental health topics to psychiatrists and other medical professionals.The Journal of Clinical Psychiatry is the leading psychiatric resource for clinical information and covers disorders including depression, bipolar disorder, schizophrenia, anxiety, addiction, posttraumatic stress disorder, and attention-deficit/hyperactivity disorder while exploring the newest advances in diagnosis and treatment.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
