38 Day Toxicity Study of Subcutaneous Asparaginase in Beagle Dogs

2022年2月 项目摘要/摘要 天冬酰胺酶是一种被指定为诱导多中心淋巴瘤缓解的母体。 狗。到目前为止，还没有关于天冬酰胺酶在狗身上使用的毒性数据。AS 天冬酰胺酶作为一种新的动物药物的批准程序的一部分，一项目标动物安全研究 已向食品和药物管理局兽医中心提出建议，并得到其同意 药品管理局。这项研究涉及皮下注射天冬酰胺酶以 32只狗(16只/性别)，随机分为4组，每组4只/性别/组，以确定其毒性 天冬酰胺酶，每周服用一次，共6次(第1、8、15、22、29和36天)，范围为 0 IU/kg/剂量(对照动物)，至400、800或1600 IU/kg/剂量。动物将被终止，并 在第38天尸检。给予天冬酰胺酶的局部和全身影响将是 对活体和尸检都进行了编目。此外，因为天冬酰胺酶是一种异源蛋白质 (它是从大肠杆菌中提取的)，研究动物每天都会被观察是否有迹象表明 过敏反应和血液样本将在整个研究期间从 所有研究动物用于随后确定是否存在抗药物抗体 过敏性反应可通过活体观察或尸检检测到。归根结底，数据 本研究收集的数据将以摘要的形式在《动物安全》的 经批准的产品处方信息，以供开处方的兽医使用。

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.