Supplement to: Medication Development for the Treatment of Alcohol Use Disorder - U01AA028957

补充：治疗酒精使用障碍的药物开发 - U01AA028957

• 批准号: 10840525
• 负责人: SUSAN E. BERGESON
• 金额: $ 15.3万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2024-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10840525
• 关键词: Address; Animals; Chromatography; Clinical Treatment; Collaborations; Competitive Bidding; Complex; DSM-V; Dangerousness; Development; Disease; Dose; Ethanol; Ethers; FDA approved; Future; Goals; Grant; Innate Immune System; Lead; Medical; Methods; Minocycline; Morbidity - disease rate; National Institute on Alcohol Abuse and Alcoholism; Output; Patients; Persons; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Physical Dependence; Production; Risk; Rivers; Tetracyclines; Withdrawal Symptom; alcohol use disorder; cost; experience; first-in-human; high risk drinking; improved; manufacture; off-label use; pre-clinical; public health relevance; safety testing; success; therapy development

Nearly 15 million people in the US and ~100 million worldwide suffer from AUD. Over 5% of all medical morbidities share an ethanol-related risk. Although there are three FDA approved drugs to treat AUD, and several others are used off-label, medications have shown only modest success (in ~20% of patients treated). As a consequence, there is an urgent need for new pharmacotherapeutics across the DSM-V AUD spectrum. Our approach in U01AA028957 was a straightforward medchem plan, IND-enabling studies followed by first in human safety tests. A supplement is requested to meet unexpected direct expenses for Original Aim 1 and 2 with benefit to aims 3-4. [Original Aims: 1: Development of manufacturing standards; 2: Completion of pre-clinical IND enabling studies; 3: Phase I clinical trial; single- ascending dose; 4: Phase I clinical trial; multiple-ascending dose.] Specifically, based on estimations from Charles Rivers Lab and our consultants, we had anticipated needing 1 kg of compound to complete the animal studies of aim 2. As such, the purification method we developed would have sufficed. However, we now need to significantly upscale production. Curia Global is a company that produces metric tons of minocycline and has competitively bid to complete the GMP drug needs for this grant. However, we need them to eliminate a purification step, which, if successful, will dramatically reduce the future costs of the higher need. Given their experience with tetracycline and in further discussions with them, they are confident they can remove the problematic chromatographic purification step during tech transfer. The dividend for Aims 3 and 4 will be that the commensurate costs will be ~$16,000 rather than ~$60,000 per kg. These costs were not covered in the original proposal. The goal of the supplement is: To improve efficiency and increase output from 1 to approximately 15 kg butylether minocycline in support of both pre-IND and phase 1 activities.

在美国，近1500万人和全世界约有1亿人患有AUD。超过5％的医疗 病因具有与乙醇相关的风险。尽管有三种FDA批准的药物可以治疗AUD，并且 其他几个被标签使用，药物仅显示出适度的成功（在约20％的患者中 治疗）。结果，迫切需要在DSM-V中使用新的药物治疗药 音频频谱。我们在U01AA028957中的方法是一个直接的Medchem计划 研究随后是人类安全测试。要求补充以达到意外的直接 原始目标1和2的费用，有利于目标3-4。 [原始目的：1：开发 制造标准； 2：完成临床前IND促进研究； 3：I期临床试验；单身的- 上升剂量； 4：I期临床试验；特别是根据 查尔斯·里弗斯（Charles Rivers）实验室和我们的顾问，我们预计需要1公斤的化合物来完成 AIM 2的动物研究。因此，我们开发的纯化方法就足够了。然而， 现在，我们需要显着高档生产。 Curia Global是一家生产公制的公司 Minocycline并有竞争力地竞标完成该赠款的GMP药物需求。但是，我们需要 他们消除净化步骤，如果成功，该步骤将大大降低 更高的需求。鉴于他们在四环素方面的经验以及与他们的进一步讨论，他们是 有信心他们可以在技术传输期间删除有问题的色谱净化步骤。这 目标3和4的股息将是，相应成本为约16,000美元，而不是$ 60,000 公斤。原始提案中没有涵盖这些费用。补充的目标是：改进 效率并将产量从1增加到约15 kg丁酯米诺环素，以支持这两者 预先印度和第1阶段活动。