Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, New York, New York.
Intra-Cellular Therapies, Inc., New York, New York; 3-D Pharmaceutical Consultants, San Diego, California.
Biol Psychiatry. 2016 Jun 15;79(12):952-61. doi: 10.1016/j.biopsych.2015.08.026. Epub 2015 Aug 31.
An urgent need exists for new treatments of schizophrenia that are effective against a broad range of symptoms and free of limiting safety issues. ITI-007 is a new molecular entity with a pharmacologic profile that combines dose-related monoamine modulation with phosphorylation of intracellular signaling proteins.
A phase II randomized, double-blind, placebo-controlled, and active-controlled trial was conducted at eight sites in the United States with randomization of 335 acutely psychotic adults with schizophrenia. ITI-007 (60 mg and 120 mg), placebo, and risperidone, included for assay sensitivity, were evaluated as monotherapy for 4 weeks. The primary outcome measure was the Positive and Negative Syndrome Scale total score, with secondary analyses conducted on symptom subscales.
ITI-007 60 mg (p = .017, effect size = .4) and risperidone (p = .013, effect size = .4) demonstrated antipsychotic efficacy superiority over placebo on the primary end point. The results of secondary analyses reflected improvements in negative and depressive symptoms by ITI-007 60 mg. ITI-007 120 mg did not separate from placebo. However, both doses of ITI-007 were well tolerated in this patient population, as evidenced by low discontinuation and adverse event rates, and were associated with a benign metabolic profile as evidenced by significantly lower levels of prolactin, fasting glucose, total cholesterol, and triglycerides than risperidone.
The mechanistically novel investigational drug ITI-007 was effective for the treatment of schizophrenia and comparable with placebo on safety measures in this trial. Secondary analyses indicated that ITI-007 improved negative and depression symptoms and might have expanded therapeutic efficacy in comparison with current antipsychotic drugs.
目前迫切需要新的治疗方法来治疗精神分裂症，这种方法不仅要对多种症状有效，而且不能有严重的安全问题。ITI-007 是一种新的分子实体，其药理学特征是剂量相关的单胺调节与细胞内信号蛋白磷酸化相结合。
在美国的 8 个地点进行了一项为期 4 周的、随机、双盲、安慰剂对照和阳性对照的 II 期临床试验，共纳入 335 名急性精神病性精神分裂症患者。ITI-007（60mg 和 120mg）、安慰剂和利培酮（用于检测灵敏度）被评估为单药治疗。主要结局测量是阳性和阴性症状量表总分，对症状子量表进行了二次分析。
ITI-007 60mg（p=0.017，效应大小=0.4）和利培酮（p=0.013，效应大小=0.4）在主要终点上显示出优于安慰剂的抗精神病疗效。ITI-007 60mg 的二次分析结果反映了阴性和抑郁症状的改善。ITI-007 120mg 与安慰剂无差异。然而，在这一患者群体中，两种剂量的 ITI-007 均具有良好的耐受性，表现在低停药率和不良事件发生率，并且与良性代谢特征相关，表现为催乳素、空腹血糖、总胆固醇和甘油三酯水平显著低于利培酮。
在这项试验中，机制新颖的研究药物 ITI-007 对精神分裂症的治疗有效，且在安全性测量方面与安慰剂相当。二次分析表明，ITI-007 改善了阴性和抑郁症状，与目前的抗精神病药物相比，可能扩大了治疗效果。
