38 Day Toxicity Study of Subcutaneous Asparaginase in Beagle Dogs

比格犬皮下注射天冬酰胺酶的 38 天毒性研究

• 批准号: 10563091
• 负责人: Charles Ralph Krikorian
• 金额: $ 25万
• 依托单位: ASSISI RESEARCH LABORATORIES, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10563091
• 关键词: 38; Day; Toxicity; Study; Subcutaneous

February 2022 Project Summary/Abstract Asparaginase is MUMS Designated for the induction of remission in multicentric lymphoma in dogs. To date, toxicity data regarding the use of asparaginase in dogs has not been available. As part of the approval process for asparaginase as a new animal drug, a Target Animal Safety Study has been proposed to, and concurred with by, the Center for Veterinary Medicine of the Food and Drug Administration. The study involves the subcutaneous administration of asparaginase to thirty-two (16/sex) dogs, randomly assigned to 4 groups of 4/sex/group to determine the toxicity of asparaginase when given once weekly for 6 doses (Days 1, 8, 15, 22, 29 and 36) ranging from 0 IU/kg/dose (control animals), to 400, 800, or 1600 IU/kg/dose. Animals will be terminated and necropsied on Day 38. Local and systemic effects of asparaginase administration will be catalogued both in-life and at necropsy. In addition, because asparaginase is a heterologous protein (it is derived from E. coli), study animals will be observed each day of the study for signs of hypersensitivity reactions and blood samples will be collected throughout the study period from all study animals for subsequent determination of the presence of anti-drug antibodies if hypersensitivity reactions are detected by in-life observations or at necropsy. Ultimately, the data collected by this study will be presented, in summary fashion, in the Animal Safety portion of the approved product prescribing information for the benefit of prescribing veterinarians.

2022年2 项目总结/摘要 门冬酰胺酶是MUMS指定用于诱导多中心淋巴瘤缓解， 狗迄今为止，尚未获得有关在犬中使用天冬酰胺酶的毒性数据。作为 天冬酰胺酶作为一种新兽药的批准过程的一部分，靶动物安全性研究 已向食品和药物管理局兽医中心提出并得到其同意， 药品监督管理总局.该研究涉及皮下给予天冬酰胺酶， 32只（16只/性别）犬，随机分配至4组，每组4只/性别/组，以测定毒性 当每周一次给药6次（第1、8、15、22、29和36天）时，天冬酰胺酶的剂量范围为 0 IU/kg/剂（对照动物）至400、800或1600 IU/kg/剂。动物将被处死， 在第38天进行尸检。天冬酰胺酶给药的局部和全身效应将被评估。 在活体和尸检时进行分类。此外，由于天冬酰胺酶是异源蛋白质， (it是由E.大肠杆菌），在研究期间每天观察研究动物的以下体征： 在整个研究期间，将从以下时间点采集超敏反应和血液样本： 所有研究动物，用于随后确定是否存在抗药抗体，如果 通过活体观察或尸检检测超敏反应。最终，数据 本研究收集的数据将以汇总方式呈现在 经批准的产品处方信息，以利于处方兽医。