Risperidone Subcutaneous Implant

描述（由申请人提供）：拟议研究的目的是开发一种利培酮皮下植入物，该植入物可提供持续3个月的治疗性血液药物水平。这种产品的好处包括改善药物依从性，如果由于治疗出现不良反应（ae）而需要停药，减少复发和提高疗效。非典型抗精神病药物已使用数年，治疗精神分裂症效果显著。然而，由于患者不坚持治疗，这些药物在维持治疗中的有效性受到限制。缺乏药物依从性已被证明与复发和再住院高度相关。随着每次复发，患者的长期预后恶化，很少能达到以前的功能水平。患者的不依从性也给美国医疗保健系统带来了额外的负担，据估计，每年的负担为23亿美元。利培酮的建议配方将通过一个小的皮下储存器，可以在一个简单的，15分钟内植入，在办公室的程序。虽然已经存在一些皮下植入技术，但它们都不适合用于利培酮或其他抗精神病药物的输送。最近的研究结果表明，86%的医疗保健提供者和50%的患者支持在该疾病区域使用植入物。本研究将通过一系列体外和体内试验验证所采用的技术，并优化配方和植入物设计。未来，同样的技术也可能用于其他抗精神病药物或其他类别的药物，这些药物可能受益于这种递送。长期作用的抗精神病制剂的临床效益已经被证明与储存制剂。相对于每日口服治疗，两周注射利培酮储存制剂可改善精神分裂症患者的治疗依从性、改善临床症状和更大程度地减少住院时间。然而，两个关键障碍阻碍了长效储存库制剂的发展：安全性问题，因为药物不能在给药后撤回，以及储存库技术在提供2-4周以上持续血液水平方面的技术限制。目前的项目旨在解决这些问题，并提供比现有仓库以下好处：提高患者依从性（3个月释放，而不是2周）；能够在需要时撤回药物（不可能使用库存配方）；优越的药代动力学特征（无波峰波谷，安全性和有效性更好）；减少侵入性（一次手术代替6次痛苦的注射）；降低成本（减少复发和就医次数）

DESCRIPTION (provided by applicant): The objective of the proposed study is to develop a subcutaneous implant of risperidone which provides consistent therapeutic blood levels of the drug for 3 months. The benefits of such product include improved medication adherence, the ability to withdraw the medication if needed due to treatment emergent Adverse Effects (AEs), fewer relapses, and improved efficacy. Atypical antipsychotics have been used for several years with great results for the treatment of schizophrenia. However, the effectiveness of these agents in maintenance treatment is limited due to patient non-adherence. Lack of medication adherence has been shown to highly correlate with relapse and re-hospitalization. With each successive relapse, the patient's long-term prognosis deteriorates and previous level of functioning is rarely achieved. Patient non-adherence also places an additional burden on the US healthcare system, which is estimated at $2.3 Billion per year. The proposed formulation of risperidone will be delivered through a small subcutaneous reservoir, which can be implanted during a simple, 15 minute, in office procedure. Although some subcutaneous implant technologies already exist, none of them is suitable for the delivery of risperidone or other antipsychotics. The results of recent studies show that 86% of healthcare providers and 50% of patients support the use of implants in this disease area. The proposed study will validate the technology employed and optimize the formulation and the implant design through a series of in-vitro and in-vivo tests. The same technology may also be used in the future for other antipsychotics or other classes of drugs that may benefit from such delivery. The clinical benefits of long acting antipsychotic formulations have already been proven with depot formulations. Relative to daily oral therapy, a two-week injectable depot formulation of risperidone is associated with improved treatment adherence, improvement in clinical symptoms, and greater reduction in hospital stays in patients with schizophrenia. However, two critical barriers have impeded the development of longer acting depot formulations: Safety issues since the drug cannot be withdrawn after administration, and technical limits of depot technology to provide consistent blood levels for more than 2-4 weeks. The current program is designed to address these problems and provide the following benefits over existing depots: Improved patient adherence (3 month release instead of 2 weeks); Ability to withdraw the medication if needed (not possible with depot formulations); Superior pharmacokinetic profile (no peaks and troughs resulting in better safety and efficacy); Reduced invasiveness (one procedure replaces 6 painful injections); Reduced cost (fewer relapses and doctor visits) PUBLIC HEALTH RELEVANCE: The proposed product will reduce relapses during maintenance treatment, improve safety, and increase overall treatment success, for patients suffering from schizophrenia. The final outcome will be an improvement in patient lives, and a reduction in overall healthcare costs.