3-Month Toxicity and Toxicokinetics Intravenous Infusion Study in Beagle Dogs Giv

比格犬 3 个月的毒性和毒代动力学静脉输注研究 Giv

• 批准号: 8787969
• 负责人: Dmytro Berezhnoy
• 金额: $ 12.5万
• 依托单位: OGENX THERAPEUTICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8787969
• 关键词: Month; Toxicity; Toxicokinetics; Intravenous; Infusion

Project Summary/Abstract Study Title: 3-Month Toxicity and Toxicokinetics (TK) Intravenous (IV) Infusion Study in Beagle Dogs Given RC-2 Beta (¿) with a 4-Week Recovery (Target Animal Safety Study) Experimental Design: This GLP (Good Laboratory Practices) study is a controlled safety study of RC-2¿ in 20 male and 20 female purpose-bred beagle dogs, approximately 4 months at the age of initiation and weighing 5kg to 11kg. Dogs will be assigned to a group using a randomization procedure and treated in one of 4 groups: Saline Control, Low Dose (1x), Mid Dose (3x), and High Dose (5x). All dose groups will have RC-2¿ administered twice weekly via a 30-minute IV infusion for 13 weeks and an assessment of the reversibility of any effects after a 4-week recovery will be studied. The standard dosing of RC-2¿ is one dose per week; however, the study is designed in accordance with the CVM/ONADE agreement to use a compressed dosing schedule of two doses per week in order to reduce the overall study length. Data collected from all animals will be used in the final audited report. Objectives/Purpose of study: The purpose of this safety study is to evaluate the toxicity and determine the TK of RC-2¿ when administered twice weekly via a 30-minute IV infusion to dogs for 13 weeks and to assess the reversibility of any effects after a 4-week recovery. The primary objective is to establish the margin of safety for RC-2¿ in dogs using a condensed dosing schedule. The secondary objective is to determine the tolerability of the drug over a 3-month period including a 4-week recovery period. The data will be utilized for FDA Conditional Approval of RC-2¿ for Canine Lymphoma and Canine Mast Cell Tumors. Justification: This is a pivotal safety study for FDA Conditional Approval for the treatment of Canine Lymphoma and Canine Mast Cell Tumors. Canine Lymphoma is the most common malignancy diagnosed in canines representing up to 24% of all neoplasms seen in dogs, affecting over 21,900 dogs per year. This disease has a median survival of 12 months with chemotherapy and 4-8 weeks without treatment. Mast cell tumors are the most common malignant skin tumor of the dog and represent over 20% of the dermal and epidermal masses diagnosed in veterinary medicine. Over 65,000 dogs are diagnosed with Mast Cell Tumors per year. The median survival time for a dog with a grade III mast cell tumor with aggressive therapy is approximately 1 year, but it is reduced to 4-6 months in the face of metastasis. The justification for this study is that previous anecdotal use of RC-2¿ in the compassionate setting, has demonstrated effectiveness and hence, it may provide a completely new approach to the effective treatment of these two devastating cancers. The study will also be used to support the Investigational Drug Application for the treatment of human lymphoma with RC-2¿. Study Site: Covance Laboratories, Inc., Madison, WI 53704-2523

项目摘要/摘要 研究标题：Beagle 3个月毒性和毒代动力学(TK)静脉(IV)输注研究 给狗服用RC-2 Beta(？)，恢复4周(目标动物安全研究) 实验设计：本GLP(良好实验室实践)研究是一项受控的安全性研究 在20只雄性和20只雌性专门饲养的比格犬中，大约4个月龄 启动年龄，体重5公斤至11公斤。狗将被分配到一个组，使用 随机分为4组：生理盐水对照组、低剂量(1X)组、中剂量(Mid)组 剂量(3倍)和高剂量(5倍)。所有剂量组都将每周两次通过 静脉输注30分钟，持续13周，并评估治疗后任何效果的可逆性 将研究4周的恢复情况。RC-2？的标准剂量是每周一次；然而， 本研究是按照CVM/ONADE协议设计的，使用压缩的 每周两剂的给药计划，以缩短总体研究时间。数据 从所有动物中收集的数据将用于最终的审计报告。 研究目的/目的：本安全性研究的目的是评估其毒性和 犬每周两次30分钟静注RC-2的TK测定 持续13周，并评估恢复4周后任何影响的可逆性。初级阶段 目的是用浓缩剂量建立RC-2在犬体内的安全范围 时间表。第二个目标是确定药物在3个月内的耐受性。 这一时期包括4周的恢复期。这些数据将被用于FDA有条件的 RC-2批准用于犬淋巴瘤和犬肥大细胞瘤。 理由：这是一项关键的安全性研究，FDA有条件地批准用于治疗 犬淋巴瘤和犬肥大细胞瘤。犬淋巴瘤是最常见的 被诊断为犬类的恶性肿瘤占犬类所有肿瘤的24%， 每年影响超过21,900只狗。这种疾病的中位生存期为12个月。 化疗和4-8周不治疗。肥大细胞瘤是最常见的 犬的恶性皮肤肿瘤，占皮肤和表皮肿块的20%以上 被诊断为兽医。每年有超过65,000只狗被诊断出患有肥大细胞瘤 年。患有III级肥大细胞肿瘤且具有侵袭性的犬的中位生存时间 治疗时间约为1年，但若有转移则缩短至4-6个月。这个 这项研究的理由是，以前在同情的背景下使用RC-2的轶事， 已经证明了有效性，因此，它可能提供一种全新的方法来 有效地治疗这两种毁灭性的癌症。这项研究还将用于支持 RC-2治疗人类淋巴瘤的研究药物应用。 研究地点：威斯康星州麦迪逊科万斯实验室公司，邮编：53704-2523