Evaluation of Iron Species in Healthy Subjects Treated with Generic and Reference Sodium Ferric Gluconate

用仿制和参比葡萄糖酸铁钠治疗的健康受试者中铁形态的评价

• 批准号: 8875255
• 负责人: MAUREEN A KANE
• 金额: $ 50万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8875255
• 关键词: Evaluation; Iron; Species; Healthy; Subjects

Project Summary: Anemia is a complication in patients with Chronic Kidney Disease (CKD). IV injection of iron colloid preparations (iron-hydroxide core complexes in carbohydrate shells) is a current FDA approved treatment regimen. One approved iron preparation is sodium ferric gluconate, manufactured under the brand name Ferrlecit®. A generic version named Nulecit® was FDA approved in March 2011. Shortly thereafter, the European Medicines Agency published a paper that proposed that generic iron preparations, including ferric gluconate, deliver increased levels of `labile iron' [also known as non-transferrin bound iron (NTBI)] leading to toxicity. Thus, clinical studies to compare in vivo levels of `labile iron' from IV delivered generic versus brand iron-formulations are urgently needed. The goal of this study is to perform a prospective, randomized, 2-way crossover study to compare plasma, total iron (TI), transferrin bound iron (TBI), and non-transferrin bound iron (NTBI) (or `labile iron') in healthy subjects treated with either Ferrlecit® (reference) or Nulecit® (generic) injections to determine if there are differences in `labile iron' concentrations between the two formulations. The effects of treatment with each complex on levels of oxidative stress and toxicity will be measured. The following specific aims will be pursued: (1) Market brand (RLD) and generic sodium ferric gluconate products will be characterized with respect to potency, impurity, and other drug product quality attributes; (2) Rigorous bio-analytical methods to determine plasma TI, TBI, and NTBI concentrations will be developed; (3) A prospective, randomized, 2-way crossover study to compare plasma TI, TBI, NTBI levels in healthy subjects treated with generic and RLD will be carried out; (4) Oxidative stress and toxicity caused by generic and RLD will be measured with in vitro and in vivo biomarkers; (5) Side effects or adverse reactions during the study period will be monitored; (6) Statistical analysis to determine whether there are any significant differences between generic and RLD in NTBI levels and others will be performed. At the conclusion of these studies, the PIs will have collected comparative in vitro data regarding the physiochemical and structural properties of the reference and generic ferric gluconate products. Clinical data that quantifies in vivo levels of free (labile or non-transferrin bound) iron, oxidative stress biomarkers and toxicity, as a function of the type of iron gluconate product delivered will also have been obtained.

项目摘要：贫血是慢性肾脏病患者的并发症 （CKD）静脉注射铁胶体制剂（氢氧化铁核心复合物）。 碳水化合物壳）是 FDA 目前批准的一种治疗方案。 制剂是葡萄糖酸铁钠，以 Ferrlecit® 品牌生产。 名为 Nulecit® 的通用版本于 2011 年 3 月获得 FDA 批准。 此后，欧洲药品管理局发表论文提出： 包括葡萄糖酸铁在内的通用铁制剂可提高“不稳定”水平 铁[也称为非转铁蛋白结合铁 (NTBI)] 导致临床毒性。 研究比较静脉输注仿制药与品牌药中“不稳定铁”的体内水平 迫切需要铁制剂。这项研究的目的是进行一项研究。 前瞻性、随机、双向交叉研究，比较血浆、总铁 (TI)、 转铁蛋白结合铁 (TBI) 和非转铁蛋白结合铁 (NTBI)（或“不稳定铁”） 使用 Ferrlecit®（参考）或 Nulecit®（非专利）治疗的健康受试者 注射以确定“不稳定铁”浓度是否存在差异 两种配方的治疗对氧化水平的影响。 将测量压力和毒性，以实现以下具体目标：(1) 市场品牌（RLD）和通用葡萄糖酸铁钠产品的特征 （二）严谨 确定血浆 TI、TBI 和 NTBI 浓度的生物分析方法 开发了一项前瞻性、随机、双向交叉研究来比较血浆 将在接受仿制药和 RLD 治疗的健康受试者中进行 TI、TBI、NTBI 水平检测； (4) 仿制药和 RLD 引起的氧化应激和毒性将在 (5) 研究期间的副作用或不良反应 (6) 统计分析以确定是否存在 仿制药和 RLD 在 NTBI 水平和其他方面的显着差异将是 在这些研究结束时，PI 将收集比较数据。 有关参考和参考的理化和结构特性的体外数据 定量体内游离水平的通用葡萄糖酸铁产品的临床数据。 （不稳定或非转铁蛋白结合）铁、氧化应激生物标志物和毒性，作为 还将获得所提供的葡萄糖酸铁产品类型的函数。