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输送，该储存器可以在一个简单的，15分钟的办公室程序中植入。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%的医生和50%的患者支持在该疾病区域使用植入物。Delpor去年获得了该项目的I期支持，目标是完成临床前概念验证（定义为PK和局部耐受性研究）。所有I期目标现已成功完成，Delpor已经证明该技术能够以零级方式输送药物，并且可以在3个多月的时间内保持稳定的血浆水平，变化最小。此外，该装置的局部安全性现已在动物身上得到证实。随着公司接近商业化，下一个重要里程碑是完成临床概念验证，即再次定义为PK和局部耐受性。拟议的研究将允许公司组装和提交IND，并验证所有必要的QA/QC方法，以实现这一里程碑。在该技术的临床验证之后，该产品将非常吸引投资者和合作伙伴，因为它将更接近批准并进一步降低风险。长效抗精神病制剂的临床益处已经被仓库制剂证实。相对于每日口服治疗，2周注射利培酮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。拟议的计划旨在解决这些问题，并提供比现有仓库更多的好处，包括将释放延长到3个月，提供撤回药物的能力，并实现更安全的PK配置文件。

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. Results of recent studies show that 86% of physicians and 50% of patients support the use of implants in this disease area. Delpor received Phase I support for this project last year with the objective to complete the preclinical proof-of- concept (defined as a PK and local tolerance study). All Phase I Aims have now been successfully completed and Delpor has demonstrated that the technology is capable of delivering the drug in a zero-order fashion and can maintain steady plasma levels with minimal variability for over 3 months. Furthermore, the local safety of the device has now been shown in animals. The next major milestone, as the company approaches commercialization, is to complete the clinical proof-of-concept which is defined again as PK and local tolerance. The proposed study will allow the company to assemble and file the IND as well as validate all the necessary QA/QC methods in order to achieve such milestone. After the clinical validation of the technology, the product will be very attractive to investors and partners as it will be closer to approval and further de-risked. The clinical benefits of long-acting antipsychotic formulations have already been proven with depot formulations. Relative to daily oral therapy, a 2-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 proposed program is designed to address these problems and provide multiple benefits over existing depots including extending the release to 3 months, offering the ability to withdraw the medication, and achieving a safer PK profile.