Risperidone Subcutaneous Implant

这项拟议研究的目标是开发一种利培酮皮下埋植剂，它可以提供 在单次给药后6个月内维持治疗血药浓度。该设备是 在一个简单的、10分钟的办公室内程序中植入，并使用局部麻醉。该产品的好处 包括更好的服药依从性、更少的复发、在需要时因以下原因撤药的能力 治疗-紧急不良事件(AEs)，无需任何启动的简单给药计划，以及 平稳的药代动力学(PK)曲线，以提高安全性和有效性。已经使用了非典型的抗精神病药物 多年来在治疗精神分裂症方面取得了很好的效果。然而，这些代理的有效性在 由于服药依从性差，维持治疗受到限制，约占所有复发的40% 以及再次住院治疗。随着每次复发，患者的长期预后恶化和 以前的运作水平很少能达到。2013年美国精神分裂症的总成本估计为 1550亿美元，所以不遵守给医疗保健系统带来了巨大的负担。 长效注射剂(LAI)的临床益处已经被证明，而LAI是 与较少的复发有关。然而，大多数LAI只持续几个星期，表演时间最长 利培酮赖片仅持续1个月。尽管更长的持续时间会带来额外的好处，但有两个关键 障碍阻碍了这种发展：(1)安全问题，因为药物在以下情况下不能撤回 管理，以及(2)LAI技术的技术限制，以在超过一年的时间内提供一致的血液水平 由于PK下降，几个星期。Delpor的植入技术旨在解决这些问题，并 实现6个月的治疗覆盖。虽然一些植入技术已经存在，但没有一项 适用于利培酮的释药。最近的研究结果表明，86%的医生和50%的 患者支持在这个疾病区域使用植入物。德尔福已收到一期和二期SBIR 对该计划的支持，最初目标是3个月系统。这些项目的目标一直是 成功完成，包括启动首个人临床试验所需的所有里程碑。这个 该公司最近成功地完成了一项I期临床试验，显示PK持平，没有任何严重的AEs。 此外，我们还可以将产品的使用期限从3个月延长到6个月。这项工作的主要目标是 第二阶段应用是将私人资金和公共资金结合起来，以完成关键的PK可比性 FDA要求提交NDA的研究和总结性人为因素研究。我们也是 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 在关键试验完成后衔接研究。这项关键研究的完成将带来 产品更接近提交保密协议。预计在完成后大约1-2年内获得市场批准 在后续的安全性研究也已经完成之后，这里提议的关键试验。

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.