Risperidone Subcutaneous Implant

利培酮皮下植入剂

基本信息

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
项目类别：
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

项目摘要

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一种利培酮皮下植入物，提供单次给药后 6 个月内药物的治疗血液浓度保持一致。通过简单的 10 分钟的局部麻醉手术进行植入。包括提高药物依从性、减少复发、在需要时撤药的能力治疗中出现的不良事件 (AE)、无需任何启动的简单给药方案以及已使用平滑的药代动力学（PK）曲线以提高安全性和有效性。多年来，这些药物在治疗精神分裂症方面取得了巨大成果。由于服药依从性差，维持治疗受到限制，约占所有复发的 40% 随着每次复发，患者的长期预后都会恶化。美国 2013 年精神分裂症的总体成本估计为 2013 年的水平。 1550 亿美元，因此不遵守规定给医疗保健系统带来了巨大的负担。长效注射剂 (LAI) 制剂的临床益处已得到证实，并且 LAI 然而，大多数 LAI 只能持续几周，且作用时间最长。利培酮 LAI 仅持续 1 个月，尽管较长的持续时间会带来额外的益处，但有两个关键因素。阻碍这种发展的障碍是：（1）安全性问题，因为药物在使用后不能撤回。管理，以及（2）LAI 技术的技术限制，无法在超过一个时间段内提供一致的血液水平。由于 PK 下降，Delpor 的植入技术旨在解决这些问题。实现 6 个月的治疗覆盖尽管一些植入技术已经存在，但还没有一个。最近的研究结果表明，86% 的医生和 50% 的人适合输送利培酮。患者支持在该疾病领域使用植入物，Delpor 已获得 I 期和 II 期 SBIR。对该计划的支持，最初针对的是 3 个月的系统这些计划的目标是。成功完成，包括启动首次人体临床试验所需的所有里程碑。该公司最近成功完成了一项 I 期临床试验，显示 PK 平稳，没有任何严重的 AE。此外，我们还能够将产品期限从 3 个月延长至 6 个月，这是我们的主要目标。 IIB期申请是结合私募基金和公募基金，完成关键的PK可比性我们还根据 FDA 的要求进行了 NDA 提交的研究和总结性人为因素研究。计划将我们现有的 cGMP 制造工艺用于商业生产，这样我们就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预计在完成后大约 1-2 年接近 NDA 提交。在后续安全研究也完成之后，我们提出了这里提出的关键试验。