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，以前的功能水平很少达到。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分钟的诊室手术中植入。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递送。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领域使用植入物。该研究将通过一系列的体外和体内试验来验证所采用的技术并优化配方和植入物设计。同样的技术将来也可能用于其他抗精神病药物或其他类别的药物，这些药物可能会从这种输送中受益。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，利培酮两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。目前的计划旨在解决这些问题，并提供以下好处超过现有的仓库：提高患者的依从性（3个月释放而不是2周）;如果需要，能够撤回药物（贮库型制剂不可能）;上级药代动力学特征（无波峰和波谷，安全性和有效性更好）;侵袭性降低（一次手术可代替6次痛苦的注射）;降低成本（减少复发和看医生的次数） 公共卫生相关性：该产品将减少维持治疗期间的复发，提高安全性，并增加精神分裂症患者的整体治疗成功率。最终的结果将是改善患者的生活，降低整体医疗成本。