Risperidone Subcutaneous Implant

描述（由申请方提供）：拟定研究的目的是开发一种利培酮皮下植入剂，可提供持续3个月的药物治疗血药浓度。这种产品的益处包括改善药物依从性、在需要时由于治疗后出现的不良反应（AE）而停用药物的能力、更少的复发和改善的功效。非典型抗精神病药已被用于精神分裂症的治疗多年，取得了很好的效果。然而，由于患者不依从，这些药物在维持治疗中的有效性有限。缺乏药物依从性已被证明与复发和再住院高度相关。随着每次连续复发，患者的长期预后恶化，并且很少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，估计每年为23亿美元。利培酮的拟定制剂将通过一个小型皮下储药器给药，该储药器可在一个简单的15分钟诊室手术期间植入。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递送。最近的研究结果表明，86%的医生和50%的患者支持在该疾病领域使用植入物。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已证明该技术能够以零级方式递送药物，并可在3个多月内保持稳定的血浆水平，变异性最小。此外，该器械的局部安全性现已在动物中得到证实。随着公司接近商业化，下一个重要的里程碑是完成临床概念验证，再次定义为PK和局部耐受性。拟议研究将允许公司组装和归档IND，并确认所有必要的QA/QC方法，以实现这一里程碑。在该技术的临床验证之后，该产品将对投资者和合作伙伴非常有吸引力，因为它将更接近批准并进一步降低风险。长效抗精神病药物制剂的临床获益已通过长效制剂得到证实。相对于每日口服治疗，利培酮2周注射贮库型制剂与精神分裂症患者治疗依从性改善、临床症状改善和住院时间大幅减少相关。然而，有两个关键障碍阻碍了长效贮库制剂的开发：安全性问题，因为药物在给药后不能撤回，以及贮库技术的技术限制，以提供超过2-4周的一致血液水平。拟定的项目旨在解决这些问题，并提供优于现有贮库的多种获益，包括将放行延长至3个月，提供停药的能力，并实现更安全的PK特征。

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.