A multi-center pivotal field study to confirm the effectiveness and safety of verdinexor for the treatment of lymphoma in dogs.

项目摘要/摘要： 拟议的研究将有助于完成对我们的新动物药物的要求 指定预期用途的应用(NADA)有效性技术部分。 研究设计 这将是一个前瞻性的、随机的、双掩蔽的、安慰剂对照的、多站点的、关键的 一项旨在评估Verdinexor治疗狗淋巴瘤的现场研究。 处理组和动物数量 在研究第0天，符合研究条件的狗将按4：1的比例随机分为IVP或CP治疗组 比率，以5块为单位。在多个研究地点将遵循单一研究方案。一个 将在所有地点招募足够数量的狗来完成这项研究 至少100例可评价病例用维地奈德治疗，25例可评价病例用维地奈德治疗 安慰剂药片。100只IVP犬和25只CP犬的可评估样本量，假设时间中值 到分别28天和7天的进展，将提供90%以上的功率(阿尔法= 0.05，双面)。为了符合统计分析的条件，每个研究地点必须完成一份 至少5个可评价病例，每个治疗组至少1个。不超过可评估的25% 病例应在任何一个地点登记。10,000项临床试验的模拟，使用 为分析指定的统计模型，生成以确定是否建议的样本 大小会有足够的能量。 统计分析：有效性终点：主要有效性变量 主要的有效性变量将是进展时间(TTP)。TTP被定义为时间 从第0天到疾病进展期。案件将被视为进展中 疾病状态如果第16.8.1.3节中对目标病变的进行性疾病的定义， 或者，如果符合第16.8.2.2节中关于非靶标病变的进行性疾病的定义。 如果狗淋巴瘤的TTP中位数是统计学上的，就会建立有效性 与安慰剂组相比，治疗组的时间明显延长。相互关系的关系 统计治疗的成功对药物的临床益处将在最后一次讨论中解决 研究报告(FSR)。 安全评估 安全性将根据体检、血清化学、血液学和尿液分析进行评估 参数和不良事件的发生。

Project Summary/Abstract: The proposed study will contribute to completing the requirements for our New Animal Drug Application (NADA) effectiveness technical section for the designated intended use. Study Design This will be a prospective, randomized, double-masked, placebo-controlled, multi-site, pivotal field study designed to evaluate verdinexor for the treatment of lymphoma in dogs. Treatment Groups and Number of Animals On study Day 0, study-eligible dogs will be randomized to the IVP or CP treatment group in a 4:1 ratio, in blocks of 5. A single study protocol will be followed at multiple study locations. A sufficient number of dogs will be enrolled in the study across all sites to complete the study with at least 100 evaluable cases treated with verdinexor and 25 evaluable cases treated with placebo tablets. An evaluable sample size of 100 IVP and 25 CP dogs, assuming a median time to progression of 28 days and 7 days respectively, will provide more than 90% power (alpha = 0.05, 2-sided). To be eligible for the statistical analysis, each study site must complete a minimum of 5 evaluable cases, at least 1 per treatment group. No more than 25% of evaluable cases should be enrolled at any one site. A simulation of 10,000 clinical trials, using the statistical model specified for the analysis, was generated to determine if the proposed sample size would have adequate power. Statistical Analysis: Effectiveness Endpoints: Primary Effectiveness Variable The primary effectiveness variable will be time to progression (TTP). TTP is defined as the time from Day 0 to time of progressive disease. A case will be considered to be in progressive disease state if either the definition of progressive disease for target lesions in section 16.8.1.3, OR, if the definition of progressive disease for non-target lesions in section 16.8.2.2, is met. Effectiveness will be established if the median TTP of lymphoma in dogs is statistically significantly longer in the treated group compared to the placebo group. Correlation of the statistical treatment success to the clinical benefit of the drug will be addressed in the Final Study Report (FSR). Safety Assessment Safety will be evaluated based on physical exam, serum chemistry, hematology and urinalysis parameters and the occurrence of adverse events.