Risperidone Subcutaneous Implant

利培酮皮下植入剂

• 批准号: 8784324
• 负责人: FRANCIS JOSEPH MARTIN
• 金额: $ 11.74万
• 依托单位: DELPOR, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8784324
• 关键词: Accounting; Acids; Address; Adherence; Adoption; Adverse effects; Adverse event; Animals; Antipsychotic Agents; Area; Automobile Driving; Biological Assay; Blood; Blood drug level result; Clinical; Clinical Protocols; Development; Device Designs; Devices; Diffusion; Disease; Dose; Drug Formulations; Drug Kinetics; Effectiveness; Equation; Equilibrium; Exhibits; Health; Health Care Costs; Healthcare Systems; Hospitalization; Hydrolysis; Implant; Implantation procedure; In Vitro; Injectable; Injection of therapeutic agent; Lactic acid; Length of Stay; Maintenance; Methods; Oral; Outcome; Patient Noncompliance; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Phase I Clinical Trials; Physicians; Plasma; Polymers; Procedures; Process; Protocols documentation; Relapse; Relative (related person); Reporting; Research Personnel; Risk; Risperidone; Safety; Sampling; Schizophrenia; Site; Sterilization; Symptoms; System; Technology; Testing; Therapeutic; Time; Uncertainty; Validation; alternative treatment; analytical method; assay development; atypical antipsychotic; base; commercialization; design; implantation; improved; manufacturing process; medication compliance; method development; outcome forecast; pre-clinical; programs; prototype; research study; response; safety study; scale up; subcutaneous; success; technology validation; tool; treatment adherence

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.

描述（由申请人提供）：拟议的研究的目的是开发利培酮的皮下植入物，该植入物可提供3个月的药物治疗血液水平。这种产品的好处包括改善药物依从性，由于需要治疗后出现的不良反应（AES），较少的复发和提高疗效而撤回药物的能力。非典型抗精神病药已使用了几年，用于治疗精神分裂症。但是，由于患者的不遵守，这些药物在维持治疗中的有效性受到限制。缺乏药物依从性已显示与复发和重新住院高度相关。随着每次连续的复发，患者的长期预后会恶化，并且以前的功能水平很少实现。患者的不遵守还给美国医疗保健系统带来了额外的负担，估计为每年23亿美元。提议的利培酮配方将通过一个小的皮下储层进行交付，该储层可以在简单的15分钟的办公室手术中植入。尽管某些皮下植入物技术已经存在，但它们都不适合利培酮或其他抗精神病药。最近的研究结果表明，有86％的医生和50％的患者支持在该疾病区域使用植入物。去年，Delpor获得了对该项目的I阶段支持，目的是完成临床前概念证明（定义为PK和本地耐受性研究）。现在，所有I阶段的目标已经成功完成，Delpor证明该技术能够以零级的方式输送该药物，并且可以保持稳定的血浆水平，而在3个月中的可变性最小。此外，该设备的局部安全性现已显示在动物中。当公司接近商业化时，下一个主要的里程碑是完成临床概念验证，该临床证明再次被定义为PK和当地耐受性。拟议的研究将允许公司组装和提交IND以及验证所有必要的QA/QC方法，以实现此类里程碑。在对该技术进行临床验证之后，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危险。长效抗精神病药剂的临床益处已经通过仓库制剂证明。相对于每日口腔疗法，利培酮的2周可注射仓库配方与改善的治疗依从性，临床症状的改善以及精神分裂症患者的住院时间更大有关。但是，两个关键的障碍阻碍了更长的作用库配方的发展：安全问题，因为在给药后无法撤回该药物，并且仓库技术的技术限制以提供超过2-4周的一致血液水平。拟议的计划旨在解决这些问题，并对现有仓库提供多种好处，包括将发布延长至3个月，提供撤回药物的能力，并实现更安全的PK配置文件。