Risperidone Subcutaneous Implant

利培酮皮下植入剂

• 批准号: 8251232
• 负责人: FRANCIS JOSEPH MARTIN
• 金额: $ 34.42万
• 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 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8251232
• 关键词: Achievement; Acids; Address; Adoption; Adverse effects; Adverse event; Antipsychotic Agents; Area; Automobile Driving; Bicarbonates; Blood; Blood drug level result; Buffers; Caliber; Clinical; Data; Development; Devices; Diffusion; Dimensions; Disease; Dose; Drug Formulations; Drug Kinetics; Effectiveness; Equation; Equilibrium; Future; Goals; Health Care Costs; Health Personnel; Healthcare Systems; Hospitalization; Human; Hydration status; Hydrolysis; Implant; Implantation procedure; In Vitro; Injectable; Injection of therapeutic agent; Lactic acid; Length; Length of Stay; Maintenance; Mechanics; Membrane; Metals; Methods; Oral; Outcome; Pain; Patient Noncompliance; Patients; Pharmaceutical Preparations; Phase; Physiological; Plasma; Polymers; Porosity; Procedures; Protocols documentation; Rattus; Relapse; Relative (related person); Research; Risk; Risperidone; Safety; Schizophrenia; Series; Sterilization; Symptoms; System; Technology; Testing; Therapeutic; Time; Titania; Titanium; Uncertainty; Visit; atypical antipsychotic; compliance behavior; cost; design; implantation; improved; in vivo; medication compliance; outcome forecast; pre-clinical; programs; prototype; research and development; response; subcutaneous; success; 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. 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.

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 3 个月内一致的药物治疗血液浓度。此类产品的好处包括提高用药依从性、在因治疗出现不良反应 (AE) 需要时能够撤药、减少复发和提高疗效。非典型抗精神病药已使用多年，在治疗精神分裂症方面取得了良好的效果。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。随着每次连续的复发，患者的长期预后都会恶化，并且很少能达到以前的功能水平。患者不依从治疗也给美国医疗保健系统带来了额外负担，估计每年造成 23 亿美元的负担。拟议的利培酮配方将通过一个小型皮下储存器输送，该储存器可以在办公室进行简单的 15 分钟手术过程中植入。尽管已经存在一些皮下植入技术，但它们都不适合输送利培酮或其他抗精神病药物。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领域使用植入物。拟议的研究将通过一系列体外和体内测试来验证所采用的技术并优化配方和植入物设计。相同的技术将来也可能用于其他抗精神病药物或可能受益于这种输送的其他类别的药物。长效抗精神病药物制剂的临床益处已通过储库制剂得到证实。与每日口服治疗相比，为期两周的利培酮注射长效制剂可提高精神分裂症患者的治疗依从性、改善临床症状并大大减少住院时间。然而，有两个关键障碍阻碍了长效储库制剂的开发：由于药物在给药后无法撤回而导致的安全问题，以及储库技术在提供超过 2-4 周的稳定血液水平方面的技术限制。当前的计划旨在解决这些问题，并与现有的储存库相比具有以下优势： 提高患者依从性（释放 3 个月而不是 2 周）；如果需要的话能够撤回药物（储库制剂不可能）；卓越的药代动力学特征（无峰和谷，从而具有更好的安全性和有效性）；减少侵入性（一次手术取代 6 次痛苦的注射）；降低成本（减少复发和就诊次数） 公共健康相关性：拟议的产品将减少精神分裂症患者维持治疗期间的复发，提高安全性并提高整体治疗成功率。最终结果将是改善患者的生活并降低总体医疗费用。