Experimental Pharmacology and Chemical Studies of Nikkomycin Z

尼可霉素 Z 的实验药理学和化学研究

基本信息

  • 批准号:
    7736460
  • 负责人:
  • 金额:
    $ 35.06万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-09-01 至 2011-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Coccidioidomycosis is a regional fungal disease in desert areas of the Southwestern U.S. and is of particular importance to Arizona and California. The importance of this disease extends beyond the endemic areas due to extensive travel to these locations. Infection with Coccidioides spp. may cause illness ranging from a mild, self-limiting, pulmonary syndrome to serious or life-threatening disease. The later is more likely in patients with compromised immunity as seen following organ transplant, cancer chemotherapy, or AIDS. Complications are also seen in certain racial groups (African American and Filipino), pregnancy, and in patients receiving drugs that suppress immune function (corticosteroids, TNF antagonists). Nikkomycin Z has been declared an orphan drug by the FDA and is eligible for fast track review. In animal models, nikkomycin Z has shown potential to eradicate the fungus from lung lesions which is not seen with existing antifungal drugs. NikZ is absorbed after oral administration and was well tolerated and safe based on a single dose study completed in man. The goal of this proposal is to support further development of NikZ and complement plans for a Phase I/II study in patients with coccidioidal pneumonia. The aims of this proposal include: conduct of PK/PD studies in mice with experimental coccidioidomycosis, establishment of a GLP complient analytical laboratory and development of optimized analytical methods, and conduct of additional preclinical studies needed to support continued clinical studies. Simultaneous, planning for the next clincial study (Phase I/II) will be ongoing with support from an NIH R34 planning grant. The PK/PD studies are needed to determine the most effective dose strategy. The results can be extrapolated to humans and guided by exposure targets in mice in relation to human pharmacokinetics and existing single dose safety results. NikZ has stability problems in biological fluids and further assay development is needed before future human studies are performed to define handling procedures and ensure reliability given limitations in clinical settings. Moreover, a GLP facility will be needed and will serve as a core laboratory for all studies ongoing with NikZ. The FDA is requiring drug metabolism/drug interaction screening before any treatment studies are initiated, and screening for cardiac ion channel effects is also needed. The planned studies will pave the way for continued development. Project Narrative: Coccidioidomycosis (Valley Fever) is a fungal infection occurring in the southwestern U.S. and affecting residents as well as visitors. Although most affected people develop only mild symptoms that resolve without treatment, some will develop prolonged and sometimes serious illness. Currently available therapies do not fully control this disease, thus our goal is to further study a new drug that represents a promising new therapy for Valley Fever.
描述(由申请人提供):球孢子菌病是美国西南部沙漠地区的一种区域性真菌疾病,对亚利桑那州和加利福尼亚州尤为重要。这种疾病的重要性超出了流行地区,因为人们经常到这些地方旅行。感染球虫可引起从轻微的自限性肺部综合症到严重或危及生命的疾病。后者更有可能发生在器官移植、癌症化疗或艾滋病后免疫力低下的患者身上。并发症也见于某些种族群体(非裔美国人和菲律宾人)、妊娠和接受抑制免疫功能药物(皮质类固醇、肿瘤坏死因子拮抗剂)的患者。Nikkomycin Z已被FDA宣布为孤儿药,并有资格获得快速通道审查。在动物模型中,nikkomycin Z已显示出根除肺部病变真菌的潜力,这是现有抗真菌药物所没有的。NikZ在口服后被吸收,并且根据在男性中完成的单剂量研究具有良好的耐受性和安全性。该提案的目标是支持NikZ的进一步开发,并补充球虫肺炎患者的I/II期研究计划。本提案的目的包括:对实验性球孢子菌病小鼠进行PK/PD研究,建立GLP完备的分析实验室,开发优化的分析方法,并进行额外的临床前研究,以支持继续的临床研究。同时,下一个临床研究(I/II期)的计划将在NIH R34计划拨款的支持下进行。需要进行PK/PD研究以确定最有效的剂量策略。结果可以外推到人类,并以小鼠暴露靶点为指导,与人类药代动力学和现有的单剂量安全性结果有关。NikZ在生物液体中存在稳定性问题,在进行未来的人体研究之前,需要进一步开发检测方法,以确定处理程序,并确保临床环境中存在局限性的可靠性。此外,将需要一个GLP设施,并将作为与NikZ正在进行的所有研究的核心实验室。FDA要求在任何治疗研究开始之前进行药物代谢/药物相互作用筛选,也需要筛选心脏离子通道效应。计划中的研究将为继续发展铺平道路。

项目成果

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JOHN N GALGIANI其他文献

JOHN N GALGIANI的其他文献

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{{ truncateString('JOHN N GALGIANI', 18)}}的其他基金

Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis
人类播散性球孢子菌病的免疫遗传学基础
  • 批准号:
    9457306
  • 财政年份:
    2017
  • 资助金额:
    $ 35.06万
  • 项目类别:
Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis
人类播散性球孢子菌病的免疫遗传学基础
  • 批准号:
    9884535
  • 财政年份:
    2017
  • 资助金额:
    $ 35.06万
  • 项目类别:
An Avirulent Arthroconidial Vaccine Candidate to Prevent Human Coccidioidomycosis
一种预防人类球孢子菌病的无毒节分孢子疫苗候选物
  • 批准号:
    9360833
  • 财政年份:
    2017
  • 资助金额:
    $ 35.06万
  • 项目类别:
Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis
人类播散性球孢子菌病的免疫遗传学基础
  • 批准号:
    9258955
  • 财政年份:
    2017
  • 资助金额:
    $ 35.06万
  • 项目类别:
Coccidioides Proteins as Vaccine Antigens and Diagnostic Biosignatures
球孢子菌蛋白作为疫苗抗原和诊断生物特征
  • 批准号:
    8260265
  • 财政年份:
    2011
  • 资助金额:
    $ 35.06万
  • 项目类别:
Nikkomycin Z treatment of early coccidioidal pneumonia: Phase II clinical trial
尼可霉素 Z 治疗早期球孢子菌肺炎:II 期临床试验
  • 批准号:
    7925199
  • 财政年份:
    2010
  • 资助金额:
    $ 35.06万
  • 项目类别:
Coccidioides Proteins as Vaccine Antigens and Diagnostic Biosignatures
球孢子菌蛋白作为疫苗抗原和诊断生物特征
  • 批准号:
    7675204
  • 财政年份:
    2009
  • 资助金额:
    $ 35.06万
  • 项目类别:
Experimental Pharmacology and Chemical Studies of Nikkomycin Z
尼可霉素 Z 的实验药理学和化学研究
  • 批准号:
    7406159
  • 财政年份:
    2008
  • 资助金额:
    $ 35.06万
  • 项目类别:
Nikkomycin Z Treatment for Coccidioidomycosis
尼可霉素 Z 治疗球孢子菌病
  • 批准号:
    7187295
  • 财政年份:
    2006
  • 资助金额:
    $ 35.06万
  • 项目类别:
Host control in Coccidioidomycosis
球孢子菌病的宿主控制
  • 批准号:
    6904461
  • 财政年份:
    2004
  • 资助金额:
    $ 35.06万
  • 项目类别:
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