Risperidone Subcutaneous Implant

本研究的目的是开发一种利培酮皮下植入剂， 单次给药后6个月内药物的治疗血药浓度保持一致。该装置 在一个简单的，10分钟，在办公室程序与局部麻醉植入。产品的受益 包括改善药物依从性，减少复发，如果需要， 治疗后出现的不良事件（AE），无需任何启动的简单给药方案，以及 平稳的药代动力学（PK）曲线，以提高安全性和有效性。非典型抗精神病药物已经被用于 多年来在治疗精神分裂症方面取得了很好的效果。然而，这些药物在 由于药物依从性差，维持治疗有限，占所有复发的40%左右 和再次住院治疗。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。美国2013年精神分裂症的总成本估计为 1550亿美元，因此不遵守给医疗保健系统带来了巨大的负担。 长效注射剂（LAI）制剂的临床益处已经得到证实，并且莱什是 与较少复发相关。然而，大多数莱什只持续几个星期，最长的作用 利培酮LAI仅持续1个月。虽然更长的期限将提供额外的好处，但两个关键的 阻碍这种发展的障碍有：（1）安全性问题，因为药物不能在 管理，和（2）LAI技术的技术限制，以提供一致的血液水平超过一个 几周后，由于PK下降。Delpor的植入技术旨在解决这些问题， 达到6个月的治疗覆盖率。虽然一些植入技术已经存在，但没有一种 适用于利培酮的递送。最近的研究结果表明，86%的医生和50%的 患者支持在该疾病领域使用植入物。Delpor已收到第一阶段和第二阶段SBIR 该计划最初针对3个月的系统。这些方案的目的是 成功完成，包括启动首次人体临床试验所需的所有里程碑。的 公司最近成功完成了一项I期临床试验，显示PK平稳，无任何严重AE。 此外，我们已经能够将产品期限从3个月延长到6个月。的主要目标 IIB期申请是将联合收割机私人和公共资金结合起来，以完成关键的PK可比性 研究和FDA要求的总结性人为因素研究，以提交NDA。我们也 计划将我们现有的cGMP生产工艺用于商业生产，因此我们可以避免任何 关键试验完成后的桥接研究。关键性研究完成后， 产品更接近NDA提交。预计在完成后约1 - 2年内获得市场批准 在完成后续安全性研究后，我们将在此提出关键性试验。

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.