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: 9352557
• 负责人: MAUREEN A KANE
• 金额: $ 21.14万
• 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/9352557
• 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：贫血是慢性肾脏疾病患者的并发症 （CKD）。静脉注射铁胶体制剂（铁 - 羟化核心核心复合物 碳水化合物壳）是当前的FDA批准治疗方案。一个批准的铁 制剂是以品牌Ferrecit®制造的铁葡萄糖酸钠。 2011年3月，FDA批准了一个名为Nulecit®的通用版本。不久 此后，欧洲药品局发表了一篇论文，提出了 包括葡萄糖酸铁在内的通用铁制剂可提供增加的不稳定 铁'[也称为非转铁蛋白结合的铁（NTBI）]导致毒性。那，临床 研究比较IV提供的通用与品牌的体内“不稳定铁”水平的研究 迫切需要铁形成。这项研究的目的是执行 前瞻性，随机的2路交叉研究比较血浆，总铁（Ti）， 铁蛋白结合的铁（TBI）和非转铁蛋白结合的铁（NTBI）（或“弱铁”） 由Ferrlecit®（参考）或Nulecit®（eneric）处理的健康受试者 注射以确定“不稳定铁”浓度之间是否存在差异 两个公式。用每个复合物处理对氧化水平的治疗对 将测量压力和毒性。将追求以下具体目标：（1） 市场品牌（RLD）和通用钠葡萄糖酸钠产品将被描述 关于效力，杂质和其他药物产品质量属性； （2）严格 确定血浆TI，TBI和NTBI浓度的生物分析方法将是 发达; （3）一项前瞻性，随机的2路交叉研究，以比较等离子体 将在接受通用和RLD治疗的健康受试者中的Ti，TBI，NTBI水平； （4）将通过一般和RLD引起的氧化应激和毒性。 体内生物标志物； （5）研究期间的副作用或不良反应 期间将受到监控； （6）统计分析以确定是否有任何 NTBI级别的通用和RLD之间的显着差异将是 执行。这些研究结束时，PI将在 有关参考的生理化学和结构特性的体外数据 通用铁葡萄糖酸酯产物。量化体内自由水平的临床数据 （不稳定或非转移蛋白结合）铁，氧化应激生物标志物和毒性，作为一种 还将获得输送的铁葡萄糖酸酯产物类型的功能。