THE SYNTHESIS AND PRECLINICAL STUDIES OF NEW TREATMENTS FOR NEURODEGENERATIVE DISEASE, DIABETES MELLITUS, CONGESTIVE HEART FAILURE, ONCOLOGIC AND IMMUNOLOGIC DISEASES

神经退行性疾病、糖尿病、充血性心力衰竭、肿瘤和免疫疾病新疗法的综合和临床前研究

• 批准号: 8930681
• 负责人: CAROL E GREEN
• 金额: $ 8.86万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8930681
• 关键词: Alzheimer' s Disease; Canis familiaris; Clinical Protocols; Congestive Heart Failure; Contracts; Diabetes Mellitus; Disease; Dose; Double-Blind Method; Drug Kinetics; Human; Immune System Diseases; Intramural Research Program; Intravenous; Medical; Mus; Neurodegenerative Disorders; Oral; Pharmaceutical Preparations; Phase I Clinical Trials; Placebo Control; Placebos; Plasma; Rattus; Safety; Sampling; Sodium Chloride; Staging; Tartrates; Time; Toxic effect; aged; design; genotoxicity; healthy volunteer; phase 1 study; preclinical safety; preclinical study; volunteer

(-)-Bisnorcymserine (BNC) is a new Alzheimer’s disease (AD) experimental drug developed within the Intramural Research Program (IRP) of NIA for late stage disease - for which effective new drugs represent a current medical need. The preclinical safety profile of BNC has been determined from: single oral and intravenous toxicity studies in mice, rats and dogs; repeated dose oral toxicity studies of up to 14 days in rats and dogs; and genotoxicity studies. The results of these studies support the safety of BNC in humans. Additionally, BNC demonstrated valuable actions across a number of preclinical studies - supportive of its potential value in humans with AD. BNC is being administered in a classical single dose escalation first in human phase 1 study undertaken within IRP/NIA. Specifically, in accord with an approved clinical protocol, and with IND No. 109,540 (Bisnorcymserine (BNC) for the Treatment of Alzheimer’s Disease), BNC (in the form of its tartrate salt) is being administered orally to healthy volunteers aged 55 years and older using a double-blind placebo-controlled design. The initial dose was 20 mg. The aim of the present contract was to evaluate BNC time-dependent drug levels in plasma samples obtained from the volunteers administered either BNC or a placebo in the initial round of the BNC phase 1 clinical trial to evaluate the pharmacokinetics of this new experimental AD drug.

（-）-Bisnorcymserine（BNC）是一种新的阿尔茨海默病（AD）实验药物，在NIA的校内研究计划（IRP）内开发，用于晚期疾病-有效的新药代表了当前的医疗需求。BNC的临床前安全性特征已通过以下研究确定：小鼠、大鼠和犬单次经口和静脉给药毒性研究;大鼠和犬长达14天的重复经口给药毒性研究;以及遗传毒性研究。这些研究的结果支持BNC在人体中的安全性。此外，BNC在许多临床前研究中表现出有价值的作用-支持其在AD患者中的潜在价值。 BNC正在IRP/NIA中进行的首次人体I期研究中以经典的单次剂量递增给药。具体地，根据雅阁批准的临床方案和IND No.109，540（用于治疗阿尔茨海默病的双去甲环丝氨酸（BNC）），使用双盲安慰剂对照设计，将BNC（以其酒石酸盐的形式）口服给予55岁及以上的健康志愿者。初始剂量为20 mg。 本合同的目的是评估在BNC 1期临床试验的第一轮中从给予BNC或安慰剂的志愿者获得的血浆样品中BNC时间依赖性药物水平，以评估这种新的实验性AD药物的药代动力学。