Nanodosing: A path to higher sensitivity and lower toxicity pharmaceuticals

纳米剂量：获得更高灵敏度和更低毒性药物的途径

基本信息

批准号：
7328486
负责人：
JAMES F KRONAUGE
金额：
$ 13.08万
依托单位：
MOLECULAR INSIGHT PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2008-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7328486
关键词：
Active Biological Transport Adrenergic Agents Adult Animals Award Biodistribution Cardiac Cells Chemicals Chemistry Child Clinical Clinical Research Clinical Trials Commit Condition Contracts Critical Pathways Cyclic GMP Cyclotrons Data Detection Development Diagnostic Diagnostic Sensitivity Documentation Dose Drug Formulations Drug Kinetics Drug Utilization Drug or chemical Tissue Distribution End Point Equipment Exposure to Funding Generic Drugs Goals Grant Guanosine Monophosphate Half-Life Heart Heart Neoplasms Human Human Volunteers I131 isotope Image Iodine Isotopes Label Legal patent Malignant Neoplasms Measures Medical center Metabolic Clearance Rate Methods Molecular Names Neuroendocrine Tumors Neurons Neurosecretory Systems New-Fill Normal tissue morphology Nude Mice Operative Surgical Procedures Organ Orphan Drugs Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Polymers Polystyrenes Procedures Process Prodrugs Production Property Radiation Radio Radioactive Radioisotopes Radiolabeled Radiopharmaceuticals Range Rattus Reaction Relative (related person)Reporting Research Ethics Committees Running S Phase Safety Sensitivity and Specificity Small Business Funding Mechanisms Small Business Innovation Research Grant Solid Solutions Staging Standards of Weights and Measures Sterility Sterilization for infection control Technology Testing Therapeutic Therapeutic Agents Therapeutic Equivalency Time Tissues Toxic effect United States Food and Drug Administration United States National Institutes of Health Validation Vial device Writing adrenergic analytical method base day dosimetry expiration healthy volunteer innovation insight metaiodobenzylguanidine noradrenaline transporter novel novel diagnostics preclinical study prospective quality assurance radiochemical radiotracer scale up success tumor tumor xenograft uptake volunteer

项目摘要

DESCRIPTION (provided by applicant): Current availability of iobenguane I 123 is limited to single doses labeled at regional radiopharmacies with variable formulations and specific activities. The objective of this Fast track phase 1/2 SBIR is to produce and perform safety testing in humans of a new diagnostic drug product formulation of iobenguane I 123. The justification for requesting Fast Track consideration is to take advantage of the synergy of developing a diagnostic version of the high specific activity iobenguane I 123 using starting materials and facilities established for the development of the therapeutic I-131 agent. The goal of this proposal is to produce and test high specific activity Ultratrace iobenguane I 123 in normal human volunteers. The low specific activity iobenguane I 123 has been shown to be useful for the detection and staging of neuroendocrine tumors in adults and children and imaging neuronal activity in the heart. The innovation in this proposal is through the use of patented solid phase technology to produce a proven diagnostic agent at extremely high specific activity to increase sensitivity and specificity and lower radiation exposure to normal organs without the pharmacologically active cold carrier compound. The FDA considers iobenguane labeled with two different isotopes of iodine [I 131 and I 123] as two distinct drugs requiring distinct regulatory applications. To meet the required quality standards for the chemistry, manufacturing and controls component of an IND application, GMP quality polymer drug precursor will be used to generate the Ultratrace diagnostic iodine- 123 agent. Analytical methods must be validated with the proposed final drug formulation to demonstrate the final drug does not interfere with tests used to define the identity, purity, and strength of the agent. The drug product solution must also be verified to be apyrogenicity and sterility before human testing can be initiated. The formulation of the final drug product will be tested for stability and bioequivalence in norepinephrine-transporter expressing cells and in animals. The required IND application will be written and submitted to the FDA and the Duke Medical Center IRB. MIP will produce clinical trial material and conduct human testing of the radioactive drug substance for safety and superiority compared to conventional iobenguane I 123 in normal healthy volunteers.

描述（由申请人提供）：Ibenguane I I 123的当前可用性仅限于具有可变配方和特定活动的区域放射性药物标记的单剂量。 The objective of this Fast track phase 1/2 SBIR is to produce and perform safety testing in humans of a new diagnostic drug product formulation of iobenguane I 123. The justification for requesting Fast Track consideration is to take advantage of the synergy of developing a diagnostic version of the high specific activity iobenguane I 123 using starting materials and facilities established for the development of the therapeutic I-131 agent.该提案的目的是在正常的人类志愿者中生产和测试高特异性活动超级iobenguane I 123。特异性活性低的活性Iobenguane I 123已被证明可用于成人和儿童的神经内分泌肿瘤的检测和分期以及心脏中的神经元活性。该提案中的创新是通过使用专利的固相技术来生产具有极高特异性活性的验证诊断剂，以提高灵敏度和特异性，并在没有药理活性的冷载体化合物的情况下对正常器官的辐射暴露较低。 FDA认为iobenguane标记了两种不同的碘同位素[I 131和I 123]是两种需要不同调节应用的不同药物。为了满足化学，IND应用的制造和控制组件所需的质量标准，GMP质量聚合物药物前体将用于生成Ultratrace诊断碘-123代理。必须用建议的最终药物制剂来验证分析方法，以证明最终药物不会干扰用于定义剂的身份，纯度和强度的测试。还必须证明药物溶液是肥大性的，并且可以在开始进行人体测试之前进行不育。最终药物的制定将测试用于去甲肾上腺素转运蛋白表达细胞和动物中的稳定性和生物等效性。所需的IND申请将编写并提交给FDA和Duke Medical Center IRB。 MIP将生产临床试验材料，并在正常的健康志愿者中与常规的Iobenguane I 123进行放射性药物的安全性和优越性进行人体测试。