Novel antiretroviral therapy delivery platform for infants and young children: oral dispensable strips (ODS)

新型婴幼儿抗逆转录病毒治疗递送平台：口服一次性试纸条（ODS）

• 批准号: 10483794
• 负责人: EDWARD G MALISKI
• 金额: $ 21.68万
• 依托单位: OAK THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483794
• 关键词: 15 year old; Adherence; Adhesions; Animal Model; Anti-Retroviral Agents; Antiviral Therapy; Biological Availability; Caregivers; Cessation of life; Child; Childhood; Choking; Combined Modality Therapy; Computing Methodologies; Dose; Drug Kinetics; Encapsulated; Excipients; Film; Formulation; Goals; Gold; HIV; HIV Infections; HIV antiretroviral; HIV therapy; High Pressure Liquid Chromatography; Human; Immune; In Vitro; Infant; Lamivudine; Legal patent; Lipids; Liposomes; Liquid substance; Masks; Medical; Medicine; Micelles; Modeling; Mothers; Oral; Oral cavity; Palate; Patients; Perinatal; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Plant Roots; Polymers; Population; Preparation; Property; Prophylactic treatment; Rattus; Reference Standards; Refrigeration; Regimen; Regression Analysis; Risk; Sampling; Small Business Innovation Research Grant; Sweetening Agents; Tablets; Taste Perception; Technology; Test Result; Testing; Therapeutic; Toxicology; Virus; Water; Woman; Zidovudine; abacavir; antiretroviral therapy; barrier to care; base; comparative; crosslink; design; global health; in vivo; in vivo evaluation; neonate; novel; patient privacy; pediatric patients; pharmacokinetics and pharmacodynamics; physical property; predictive modeling; preventive intervention; prophylactic; social stigma; standard care

PROJECT ABSTRACT Between 1.3 – 2.4 million children under 15 live with HIV and are in need of regular treatment. Estimates for HIV related deaths among children are as high as 160,00 annually and often rooted in poor patient and caregiver adherence. Causes for poor adherence are rooted in low palatability of existing formulations (liquids, fast-dissolving tablets), the complexity of preparation and administration, and issues related to patient privacy / social stigma. Oak Therapeutics, Inc., is an early-stage pharmaceutical company that specializes in formulation and manufacturing of support matrix strips composed of oral-disintegrating polymers (ODS). The goal of this proposal is to develop dissolvable strip (ODS) platform that supports multi-drug pediatric formulation and to commercialize the first ever ODS formulation for pediatric antiviral therapy consisting of Abacavir/ Lamivudine/ Dolutegravir (ALD- ODS). We have already developed ODS containing a pediatric prophylactic dose of two HIV antiretroviral drugs (AZT and NVP) with appropriate properties for administration to infants and young children, including muco-adhesion, rapid oral dispersion, and taste-masking. In this proposal we will develop a novel computational method for multi- drug ODS formulation which will be used to encapsulate and make ALD-ODS strip. Optimal ODS candidate will be compared to commercial reference standard of treatment and analyzed in an in vivo PK/PD study to determine pharmacokinetics and toxicology profiles. The final ALD-ODS product will be the first oral film to contain HIV combination regiment medications. It will also be the first to achieve the targeted criteria of an orally dissolvable product, and it will be among the first pediatric products to contain all recommended first line drugs in a single formulation with easily modified dosing to simplify administration for caregivers.

项目摘要 在15岁以下的15岁以下儿童中，患有艾滋病毒的儿童有1.3 - 240万儿童，需要定期治疗。估计 儿童中与HIV相关的死亡人数高达160,00，并且经常植根于贫穷的患者 和护理人员的依从性。依从性差的原因植根于现有的低适口性 公式（液体，快速溶解片），制备和给药的复杂性，以及 与患者隐私 /社会污名有关的问题。橡树疗法公司（Inc.）是一个早期 专门从事配方和制造支持矩阵条的制药公司 由口服分散聚合物（ODS）组成。该提议的目的是开发可溶解的 支持多药小儿配方并将其商业化的条带（ODS）平台 小儿抗病毒疗法的OD公式，由阿巴卡维尔/ lamivudine/ dolutegravir组成（ALD- ODS）。我们已经开发了含有两种HIV的小儿预防剂量的OD 抗逆转录病毒药物（AZT和NVP）具有适当的对婴儿和年轻人给药的特性 儿童，包括粘膜粘附，快速口服分散和味觉掩盖。在这个建议中，我们将 为多毒ODS公式开发一种新型的计算方法，该方法将用于 封装并制作ALD-ODS条。最佳ODS候选者将与商业相提并论 参考治疗标准并在体内PK/PD研究中进行分析以确定药代动力学 和毒理学概况。最终的ALD-ODS产品将是第一部含有HIV组合的口服膜 团药物。这也将是第一个实现可溶解的目标标准的 产品，它将是最早在 具有易于修改剂量的单个公式，以简化护理人员的管理。