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I-Corps: Longer-acting intravaginal formulation of buprenorphine

I-Corps: Longer-acting intravaginal formulation of buprenorphine
I-Corps:长效丁丙诺啡阴道内制剂
批准号:
10337527
负责人:
Thomas J. Smith
金额:
$5.49万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-09-30 至 2021-08-31

项目摘要

项目成果

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中文摘要
翻译
项目摘要 这项研究计划的广泛,长期目标是增强患有阿片类药物使用障碍的妇女的权能。 (OUD)通过开发阿片类部分激动剂的长效阴道环(IVR)制剂, - 丁丙诺啡(BUP)。快速通道提案是为了响应RFA-DA-19-019而提交的,该提案要求: 开发“现有成瘾药物的长效制剂”的解决方案。 目前用于治疗OUD的基于BUP的药物产品的方法包括每日舌下, 每月注射一次和一年两次的可植入制剂。这些处方的逐年增长 表明改进的BUP药物具有改善患者保留的显著潜力, 医疗结果。 尽管它们是有用的,但速释和长效BUP制剂都表现出次优的 药物代谢动力学(PK)曲线显示初始突释,然后是平台期。每日配方 通常存在依从性/顺应性问题,并且含有比所需多5- 10倍的药物负载, 转移潜力。长效注射和植入药物是侵入性的,需要HCP访视, 局为了解决这一未得到满足的需求,我们提出了一个“快速通道”的自主研发方法, 使用我们已建立的药物递送技术每月IVR递送BUP。 IVR Nuvaring®避孕药的商业成功提供了一个适用的案例研究。超过1 百万妇女选择IVRs而不是传统方法:比长效植入物或贴片更多。我们预计 BUP环将被寻求治疗OUD的女性的显着比例所选择。 我们的团队具有制定IVR的经验,可以使用我们的 “豆荚”技术。这项工作已导致在艾滋病毒暴露前预防领域的三个IND批准 生殖器疱疹的治疗方法有哪些?在初步工作中,我们开发了一个试点BUP播客-IVR和测试 体外实验证实其处方可行性。我们证实了BUP在动物阴道中具有生物利用度 模型PK模型表明,我们的pod-IVR可以将治疗血浆水平维持在 减少剂量和转移潜力。 第1阶段的具体目标是开发涵盖广泛释放目标的铅制剂, 在动物中进行安全性和PK试验。成功完成第一阶段的里程碑将是 动物研究的安全性和临床相关药物浓度证明。 在第二阶段,具体目标将是:在化学、制造和生产方面开展所有必要的工作, 对照(CMC);临床前动物研究;以及方案制定,以实现里程碑:研究 FDA的新药(IND)许可允许BUP pod-IVR的首次人体试验。 在这项计划成功完成后,我们会申请拨款进行一系列临床研究, 进一步证明安全性、PK和疗效。该产品的开发将为女性提供一种新颖, 在阿片类药物成瘾治疗中使用的私人和改进的治疗辅助剂,减少了转移的风险。
英文摘要
PROJECT SUMMARY The broad, long-term goal of this research program is to empower women suffering from opioid use disorder (OUD) through the development of a long-acting intravaginal ring (IVR) formulation of the opioid partial agonist -buprenorphine (BUP). The fast-track proposal was submitted in response to RFA-DA-19-019 which calls for solutions to develop “Longer-acting formulations of existing addiction medications”. The current armamentarium of BUP-based drug products for the treatment of OUD includes daily sublingual, monthly injectable, and bi-annual implantable formulations. The year-over-year increase in these prescriptions suggest that improved BUP medications hold significant potential for improving patient retention, and overall healthcare outcomes. Despite their usefulness, both immediate-release and long-acting BUP formulations demonstrate sub-optimal pharmacokinetic (PK) profiles displaying an initial burst release followed by plateauing. The daily formulations often suffer from adherence/compliance issues and contain 5-10X more drug loading than required, creating diversion potential. Long-acting injectable and implantable medications are invasive, and require HCP visits for administration. To address this unmet need, we propose a “fast-track” IND-enabling approach to develop a monthly IVR delivering BUP using our established drug delivery technology. The commercial success of the contraceptive IVR Nuvaring® provides an applicable case study. More than 1 million women choose IVRs over traditional methods: more than long-acting implants or patches. We expect that a BUP ring will be chosen by a significant percentage of women seeking treatment for OUD. Our team has experience formulating IVRs to deliver a wide variety of small and large molecules using our “pod” technology. This work has resulted in three IND approvals in the fields of HIV pre-exposure prophylaxis (PrEP) and the treatment of genital herpes. In preliminary work, we developed a pilot BUP pod-IVR and tested it in vitro to confirm its formulation feasibility. We confirmed that BUP is vaginally bioavailable in an animal model. PK modeling indicates that our pod-IVR can maintain therapeutic plasma levels at a substantially reduced dose and diversion potential. The specific aims of Phase 1 are to develop lead formulations across a broad range of release targets and to perform safety and PK testing in animals. The milestone for successful completion of Phase 1 will be the demonstration of safety and clinically relevant drug concentrations from the animal study. In Phase 2, the specific aims will be: to carry out all of the necessary work in chemistry, manufacturing and controls (CMC); pre-clinical animal studies; and protocol development to allow the milestone: Investigational New Drug (IND) allowance from the FDA allowing the first-in-human testing of a BUP pod-IVR. Following successful completion of this project, we will seek funding to carry out a series of clinical studies to further demonstrate safety, PK, and efficacy. The development of this product will provide women a novel, private and improved therapeutic adjunct in the treatment of opiate addiction with reduced risk for diversion.
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Longer-acting intravaginal formulation of buprenorphine
  • 批准号:
    10472754
  • 项目类别:
  • 资助金额:
    $84.53万
  • 财政年份:
    2020
  • 负责人:
    Thomas J. Smith
  • 依托单位:
Longer-acting intravaginal formulation of buprenorphine
  • 批准号:
    10454496
  • 项目类别:
  • 资助金额:
    $84.53万
  • 财政年份:
    2020
  • 负责人:
    Thomas J. Smith
  • 依托单位:
Longer-acting intravaginal formulation of buprenorphine
  • 批准号:
    10158129
  • 项目类别:
  • 资助金额:
    $25.37万
  • 财政年份:
    2020
  • 负责人:
    Thomas J. Smith
  • 依托单位:
IND-enabling preclinical development of a sustained-release Pritelivir intravaginal ring for the treatment and prophylaxis of Genital Herpes in women
  • 批准号:
    9906167
  • 项目类别:
  • 资助金额:
    $100.0万
  • 财政年份:
    2018
  • 负责人:
    Thomas J. Smith
  • 依托单位:
海外基金