A Bioequivalence Study of Two Different Formulations of Chlorambucil in Beagle Dogs

苯丁酸氮芥两种不同制剂在比格犬中的生物等效性研究

• 批准号: 10557381
• 负责人: Sarah Wade
• 金额: $ 25万
• 依托单位: EIRGEN PHARMA LIMITED
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10557381
• 关键词: Bioequivalence; Study; Two; Different; Formulations

Chronic Lymphocytic Leukemia (CLL) in dogs represents an unmet veterinary need. The literature reports a response rate of 70% to protocols using vincristine, prednisone, and chlorambucil combinations; with chlorambucil as the maintenance drug. However, despite therapy for CLL being generally rewarding, the mainstay treatment, chlorambucil, is not an FDA approved drug for veterinary use. Presently, chlorambucil licensed for human use is being used off-label, however currently available tablet sizes, 2 mg, of chlorambucil present a challenge for treating dogs at standard prescribed dosages. Due to this challenge, unregulated compounded chlorambucil products, with reports of varying potency and stability, are in wide use in veterinary care with increased risk to the animal population, as well as the owners, pharmacists, and the veterinarians handling these compounded products. As a result, there is a clinical need for a veterinary specific chlorambucil product, developed and manufactured to the highest quality and safety standards, and at the appropriate strength to facilitate accurate dosing in small animals. Chlorambucil 1 mg tablets are being developed to address the limitations of the 2 mg tablets licensed for human use. This product is a Minor Use and Minor Species (MUMS) designated investigational product that is eligible for conditional approval. The proposed study will contribute to completing the requirements of the safety technical section for the designated intended use in dogs with CLL. The safety of chlorambucil 1 mg tablets for the treatment of CLL has been previously established in a target animal safety study using the reference product. This bioavailability study is designed to evaluate the in vivo comparability of two formulations, termed test and reference, of chlorambucil 1 mg tablets in healthy dogs thereby enabling bridging of the previously established safety information of the reference product to the test product. This study will be a randomised, non-terminal GLP (Good Laboratory Practices) study in purpose-bred beagle dogs. The primary outcome variables will be AUC(0-t) and Cmax.

犬慢性淋巴细胞白血病（CLL）代表了未满足的兽医需求。的 文献报道，使用长春新碱、泼尼松和 苯丁酸氮芥复方制剂;苯丁酸氮芥作为维持药物。但尽管 CLL的治疗通常是有益的，主要的治疗，苯丁酸氮芥，不是一种有效的治疗方法。 FDA批准的兽药。目前，苯丁酸氮芥被许可用于人类使用， 在标签外使用，然而，目前可用的片剂尺寸，2毫克，苯丁酸氮芥存在 以标准规定剂量治疗犬的挑战。由于这一挑战， 具有不同效力和稳定性的报道的复合苯丁酸氮芥产品广泛应用于 在兽医护理中使用，对动物种群以及主人的风险增加， 药剂师和处理这些复合产品的兽医。结果是 临床需要一种兽用苯丁酸氮芥产品，开发和生产， 最高的质量和安全标准，并在适当的强度，以方便准确 在小动物中给药。 正在开发苯丁酸氮芥1 mg片剂，以解决2 mg片剂的局限性 许可供人类使用。本产品是指定的次要用途和次要种属（MUMS） 有条件批准的试验用药品。拟定的研究将 有助于完成安全技术部分的要求， 预期用于CLL犬。苯丁酸氮芥1 mg片剂治疗慢性乙型肝炎的安全性 先前已在靶动物安全性研究中使用参比品确立了CLL 产品本生物利用度研究旨在评价两种药物的体内可比性。 在健康犬中进行苯丁酸氮芥1 mg片剂的试验制剂和参比制剂， 能够将先前建立的参考产品的安全性信息桥接到 测试产品。本研究将是一项随机、非终末GLP（药物非临床研究质量管理规范）研究， 实践）研究。主要结局变量为AUC（0-t） 和Cmax。