Development of a 3-month implantable depot pellet of Naltrexone for the treatment of Opioid Use Disorder.

开发用于治疗阿片类药物使用障碍的 3 个月植入式纳曲酮储库颗粒。

• 批准号: 10456354
• 负责人: Kate DeVarney
• 金额: $ 345.34万
• 依托单位: BIOCORRX, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456354
• 关键词: Abstinence; Addendum; Adherence; Affect; American; Analgesics; Anti-Inflammatory Agents; Applications Grants; Award; Behavioral; Biological Assay; Cessation of life; Chemistry; Clinical; Clinical Research; Data; Development; Dose; Drug Kinetics; Ensure; Event; Formulation; Future; Grant; Histopathology; Implant; Individual; Injectable; Injections; Kenalog; Marketing; Methods; Miniature Swine; Molecular; Naltrexone; Opioid; Opioid Antagonist; Opioid Receptor; Overdose; Pathology Report; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Plasma; Preparation; Recovery; Regulation; Regulatory Affairs; Regulatory Pathway; Relapse; Reporting; Research Design; Russia; Safety; Serum; Site; Solid; Steroids; Suspensions; Tablets; Technology Transfer; Therapeutic; Time; TimeLine; Toxic effect; Triamcinolone; Triamcinolone Acetonide; Validation; adverse drug reaction; base; clinical development; commercialization; comparative; compliance behavior; cost; effective therapy; experience; implantation; improved; innovation; liquid chromatography mass spectrometry; meetings; method development; naltrexol; opioid epidemic; opioid mortality; opioid overdose; opioid use disorder; overdose death; prevent; programs; research and development; stability testing; subcutaneous; virtual

BioCorRx is developing BICX102, a subcutaneous solid depot pellet of the opioid antagonist naltrexone (NTX). NTX is a proven treatment for opioid use disorder (OUD). A single BICX102 implantation will provide continual blockade of opioid receptors for up to 3 months. This can prevent patients from being affected adversely by almost any opioid relapse event, while improving efficacy and adherence to behavioral programs that support long term management and recovery. The BICX102 pellet can be removed if adverse drug reactions occur. BICX102 is being developed via the 505(b)2 FDA pathway as NTX and the other ingredients have been approved individually by the FDA; and BICX102 has been in clinical use in Russia as Prodetoxone® for >12 years. This UG3-UH3 proposal comprises the steps to achieve FDA approval. 2 million+ Americans have OUDs, with ~42,000 opioid overdose deaths (2016). The opioid epidemic cost $504 billion in 2015. ~91% of those in recovery experience relapse, and 80% do so within one month. Long-term abstinence is difficult to achieve due to poor compliance to effective therapies like NTX tablets and monthly injections. Our innovative solution is BICX102: a safe and effective 3-month subcutaneous depot pellet/implant containing NTX (1000 mg) that is less reliant on patient compliance. FDA guidance has indicated that they may rely on our proposed studies and existing data on BICX102 and its ingredients for the basis for 505(b)2 approval. BioCorRx has a team of experts in opioid treatment, regulation, CMC, nonclinical, clinical development and regulatory affairs to complete this project using outstanding facilities that are routinely used in the studies proposed. Aim 1: Chemistry Manufacturing and Controls (CMC): BICX102; Comprehensive Plan for Formulation Development, Technology Transfer, Clinical Batch Manufacture, FDA Registration Batch Manufacture and Stability Testing. Deliverable 1: Establish GMP facility to manufacture drug product (3-month Naltrexone/TCA Implant) for research and development and commercialization. Aim 2: Pivotal GLP Safety, Pharmacokinetic Study of BICX102, Revia, and Kenalog. Deliverable 2: Submission of IND application to the FDA for review. UG3 Transition Milestone: Successful approval of the IND by the FDA to proceed to the clinical stage. Aim 3: Comparative Single and Multiple Dose Pharmacokinetics of 3-month BICX102 Naltrexone Depot. Deliverable 3: Sustained release naltrexone serum levels above 1-2 ng/ml for up to 3 months. UH3 Milestone: Submission of 505(b)2 NDA application to FDA for marketing approval. Conclusion: Getting BICX102 to the market quickly is a national priority which necessitates effective and timely interactions between BioCorRx and the FDA. This milestone driven grant proposal is outstanding because it is following a 505(b)2 regulatory path that has been deemed acceptable by the FDA to achieve approval. We know from extensive non-clinical and clinical studies that BICX102 will be effective. This grant will result in the approval of BICX102 in Year 4 post award.

BioCorRx正在开发BICX 102，一种阿片类药物拮抗剂纳洛酮（NTX）的皮下固体贮库颗粒。 NTX是阿片类药物使用障碍（OUD）的有效治疗方法。单次BICX 102植入将提供持续的 阿片受体阻断长达3个月。这可以防止患者受到不利影响， 几乎任何阿片类药物复吸事件，同时提高疗效和遵守行为计划， 长期管理和恢复。如果发生药物不良反应，可以取出BICX 102颗粒。 BICX 102正在通过505（B）2 FDA途径开发，因为NTX和其他成分已经 BICX 102已在俄罗斯作为Prodetoxone®临床使用超过12年， 年UG 3-UH 3提案包括获得FDA批准的步骤。200多万美国人拥有 OUD，约42，000例阿片类药物过量死亡（2016年）。2015年，阿片类药物的流行造成了5040亿美元的损失。约91% 康复中的人会复发，80%的人会在一个月内复发。长期禁欲很难 由于对NTX片剂和每月注射等有效治疗的依从性差，我们的创新 BICX 102是一种安全有效3个月皮下储存的含NTX（1000 mg），其对患者依从性的依赖性较低。FDA指南表明，他们可能依赖于我们提出的 关于BICX 102及其成分的研究和现有数据，作为505（B）2批准的基础。BioCorRx具有 阿片类药物治疗、监管、CMC、非临床、临床开发和监管事务方面的专家团队， 利用拟议研究中经常使用的优秀设施完成本项目。目标1： 化学生产和控制（CMC）：BICX 102;制剂综合计划 开发、技术转让、临床批次生产、FDA注册批次生产和 稳定性测试。表1：建立GMP设施以生产制剂（3个月纳洛酮/TCA 植入物）用于研究和开发以及商业化。目的2：药物GLP安全性、药代动力学 研究BICX 102、Revia和Kennedy。表2：向FDA提交IND申请进行审查。 UG 3过渡里程碑：FDA成功批准IND进入临床阶段。目的 3：3个月BICX 102纳洛酮贮库型制剂的单次和多次给药药代动力学比较。 表3：持续释放纳洛酮血清水平高于1-2 ng/ml长达3个月。UH3 里程碑：向FDA提交505（B）2 NDA申请以获得上市批准。结论：获取 BICX 102快速上市是国家的优先事项，需要有效和及时的互动 和食品药品监督管理局的联系这一里程碑式的资助提案非常出色，因为它遵循了 505（B）2 FDA认为可接受的监管途径以获得批准。我们知道从 广泛的非临床和临床研究表明BICX 102将有效。这笔赠款将导致批准 BICX 102在四年级后奖。