Risperidone Subcutaneous Implant

利培酮皮下植入剂

• 批准号: 10024072
• 负责人: FRANCIS JOSEPH MARTIN
• 金额: $ 200万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10024072
• 关键词: Address; Adverse event; Area; Biological Assay; Blood; Blood drug level result; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Communication; Cyclic GMP; Development; Device Designs; Devices; Disease; Dose; Drug Kinetics; Effectiveness; Formulation; Funding; Health Care Costs; Healthcare Systems; Human; Implant; In Vitro; Injectable; Institutional Review Boards; Length; Local Anesthetics; Maintenance; Methods; Outcome; Patient Noncompliance; Patient Recruitments; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Physicians; Plants; Privatization; Procedures; Process; Production; Program Development; Protocols documentation; Relapse; Reporting; Risperidone; Safety; Schedule; Schizophrenia; Serious Adverse Event; Site; Small Business Innovation Research Grant; System; Tablets; Technology; Technology Transfer; Testing; Therapeutic; Validation; alternative treatment; atypical antipsychotic; clinical development; cost; design; evaporation; first-in-human; hospital readmission; implantable device; implantation; improved; manufacturing process; medication compliance; medication nonadherence; outcome forecast; programs; relapse patients; safety study; subcutaneous; success; usability; verification and validation

The objective of the proposed study is to develop a subcutaneous implant of risperidone that provides consistent therapeutic blood levels of the drug for 6 months after a single administration. The device is implanted during a simple, 10-minute, in-office procedure with local anesthetic. The benefits of the product include improved medication adherence, fewer relapses, ability to withdraw the medication if needed due to treatment-emergent Adverse Events (AEs), simple dosing schedule without any initiation required, and a smooth pharmacokinetic (PK) profile for improved safety and efficacy. Atypical antipsychotics have been used for years with great results for the treatment of schizophrenia. However, the effectiveness of these agents in maintenance treatment is limited due to poor medication adherence, which accounts for ~40% of all relapses and re-hospitalizations. With each successive relapse, the patient's long-term prognosis deteriorates and previous level of functioning is rarely achieved. The overall U.S. 2013 schizophrenia cost was estimated at $155 billion, so non-adherence places a tremendous burden on the healthcare system. The clinical benefits of long-acting injectable (LAI) formulations have already been proven, and LAIs are associated with fewer relapses. However, most LAIs only last for a few weeks, with the longest acting risperidone LAI lasting only 1-month. Although a longer duration would provide additional benefit, two critical barriers have impeded such development: (1) Safety issues since the drug cannot be withdrawn after administration, and (2) technical limits of LAI technologies to provide consistent blood levels for more than a few weeks due to declining PK. Delpor’s implant technology is designed to address these problems and achieve therapeutic coverage for 6 months. Although some implant technologies already exist, none of them are suitable for the delivery of risperidone. Results of recent studies show that 86% of physicians and 50% of patients support the use of implants in this disease area. Delpor has received Phase I and Phase II SBIR support for this program, which initially targeted a 3-month system. The aims of these programs have been successfully completed, including all milestones required for the launch of a first-in-man clinical trial. The company has recently successfully completed a Phase I clinical trial showing flat PK without any serious AEs. Furthermore, we have been able to extend the product duration from 3 to 6 months. The main objective of this Phase IIB application is to combine private and public funds in order to complete a pivotal PK Comparability study and a Summative Human Factors study as requested by the FDA for an NDA submission. We are also planning to adapt our existing cGMP manufacturing process for commercial production, so we can avoid any bridging studies after the completion of the pivotal trial. The completion of the pivotal study will bring the product closer to an NDA submission. Market approval is expected approximately 1-2 years after completion of the pivotal trial proposed here, after a follow-on safety study has also been completed.

拟议研究的目的是开发利培酮的皮下植入物 一次给药后6个月的药物治疗血液水平一致。设备是 在简单的10分钟，办公室手术中植入局部麻醉。产品的好处 包括改进的药物依从性，较少的继电器，由于需要而撤回药物的能力 治疗急剧不良事件（AES），简单的给药时间表无需任何计划，A 平滑的药代动力学（PK）剖面，以提高安全性和效率。已经使用了非典型抗精神病药 多年来，治疗精神分裂症的结果很棒。但是，这些代理在 由于药物依从性不佳，维护治疗受到限制，占所有退休的约40％ 和重新建筑。随着每次成功的缓解，患者的长期预后决定了， 以前的功能级别很少达到。估计美国整体2013年精神分裂症成本 1,550亿美元，因此不遵守的医疗保健系统造成了巨大的燃烧。 长效注射（LAI）公式的临床益处已经证明，LAI是 与较少的继电器相关。但是，大多数LAI仅持续几周，表演最长 利培酮莱仅持续1个月。尽管更长的持续时间将带来额外的好处，但两个关键 障碍阻碍了这样的发展：（1）安全问题，因为该药物在 管理和（2）LAI技术的技术限制，以提供一致的血液水平 由于PK的下降，几周。 Delpor的植入技术旨在解决这些问题和 实现6个月的治疗覆盖范围。尽管已经存在一些植入技术，但它们都不存在 适合利培酮的递送。最近的研究结果表明，医师中有86％和50％ 患者支持在该疾病区域使用牙齿。 Delpor已收到I期和II期SBIR 支持该程序，该程序最初针对3个月的系统。这些程序的目的是 成功完成，包括启动第一名临床试验所需的所有里程碑。这 公司最近成功完成了I期临床试验，该试验显示了没有任何严重AE的Flat PK。 此外，我们已经能够将产品持续时间从3个月延长。主要目标 IIB期应用程序是将私人和公共资金组合起来，以完成关键PK可比性 研究和一项总结性人为因素根据FDA要求进行NDA提交的要求。我们也是 计划调整我们现有的CGMP制造过程以进行商业生产，因此我们可以避免任何 关键试验完成后的桥接研究。关键研究的完成将带来 产品更接近NDA提交。预计完成后大约1 - 2年 在后续安全研究完成后，此处提出的关键试验也已完成。