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，需要定期治疗 对于艾滋病毒相关的儿童死亡高达160，每年且经常植根于贫穷的患者 和护理人员的依从性。 配方（液体，快速分离片），预疗法和给药的复杂性 与患者隐私 /社会污名有关的问题。 专门从事配方和制造支持矩阵条的制药公司 由口服分解聚合物组成（OD）。 支持多药小儿配方的带（ODS）平台 小儿抗病毒疗法的ODs制剂，由阿巴卡维尔/拉米夫丁/ dolutegravir（ALD-）组成 ODS）。 抗逆转录病毒（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，快速口服倾向和味觉掩盖。 开发一种用于多药ODS配方的新型计算方法，该方法将用于 封装并制作ALD BYDS条。 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。 该团药物也将是第一个实现可溶解的目标标准的 产品，它将是最早遏制已培养的第一线药物的小儿产品之一 单个配方，易于修改的剂量，以简化护理人员的管理。