Human AME study of CT1812, a small molecule in phase 2 clinical trials for the treatment of Alzheimer's disease

CT1812 的人体 AME 研究，这是一种小分子，处于治疗阿尔茨海默病的 2 期临床试验中

• 批准号: 10247968
• 负责人: ANTHONY O CAGGIANO
• 金额: $ 164.28万
• 依托单位: COGNITION THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247968
• 关键词: Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease therapeutic; Alzheimer' s disease therapy; Amyloid; Blood specimen; Brain; Caregivers; Cerebrospinal Fluid; Clinical Research; Clinical Treatment; Clinical Trials; Cognition; Collection; Conduct Clinical Trials; Disease; Disease Progression; Dose; Drug Kinetics; Ensure; Excretory function; Feces; Freezing; Future; Health Care Costs; Hepatic; Human; Impaired cognition; Impairment; Kidney; Knowledge; Medical; Memory; Metabolism; Neurons; Neurotransmitters; Oral; Patients; Pharmaceutical Preparations; Phase II Clinical Trials; Plasma; Quality of life; Radioactive; Radiolabeled; Research; Research Design; Route; Safety; Sampling; Signal Transduction; Synapses; Therapeutic; Time; United States; United States Food and Drug Administration; Urine; abeta oligomer; absorption; balance recovery; dosage; drug candidate; efficacy evaluation; expectation; improved; male; medication safety; open label; phase II trial; preservation; programs; receptor; small molecule; symptom treatment; volunteer

PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD) afflicts nearly six million people in the United States (U.S), and this number is expected to double by 2050. Disease modifying medical therapies for AD continue to be an unmet need. The symptomatic treatments currently available regulate neurotransmitter levels, slowing cognitive decline for an average of only 6 months. Cognition Therapeutics (CogRx) is developing CT1812, the first brain penetrant small molecule that selectively clears toxic beta amyloid oligomers (AβOs) from the brain into cerebrospinal fluid (CSF). CT1812's mechanism of action has the potential to halt or slow cognitive decline, significantly alleviating AD progression. CT1812 is currently in Phase 2 trials in patients. Before CogRx can proceed to larger and longer studies that evaluate efficacy, a human Absorption, Metabolism, and Excretion (AME) study must be conducted per Food and Drug Administration expectations, to establish a robust and comprehensive knowledge of CT1812's pharmacokinetics (PK) and key metabolites. Approach. The overall research design will include (Aim 1) purifying and characterizing radiolabeled CT1812 in sufficient quantities with sufficient quality; (Aim 2) conducting an open-label AME clinical trial in which up to six healthy male volunteers are given oral [14C]-CT1812, followed by plasma, urine and feces collection for up to 14 days, and (Aim 3) analyzing samples to determine mass balance recovery, PK, and identification and quantification of the relative abundances of the metabolites. CogRx's long-term objective is to develop CT1812 as a potential disease-modifying therapeutic for AD treatment. Because no AD disease-modifying therapies exist currently, CT1812 would significantly advance AD treatment armamentarium. 1

项目摘要/摘要 阿尔茨海默氏症(AD)在美国困扰着近600万人，这个数字是 预计到2050年将翻一番。治疗阿尔茨海默病的疾病改良疗法仍然是一个未得到满足的需求。这个 目前可用的对症治疗可以调节神经递质水平，减缓认知能力下降 平均只有6个月。 认知治疗公司(CogRx)正在开发CT1812，这是第一个选择性地 将有毒的β淀粉样寡聚体(AβOs)从大脑清除到脑脊液中。CT1812的S机构 行为的改变有可能阻止或减缓认知能力的下降，显著缓解AD的进展。 CT1812目前正处于二期临床试验中。在CogRx可以进行更大规模和更长时间的研究之前 评估疗效，必须按食物进行人体吸收、代谢和排泄(AME)研究 和药品监督管理局的期望，建立健全和全面的CT1812‘S知识 药物动力学(PK)和关键代谢物。 接近。整个研究设计将包括(目标1)提纯和鉴定放射性标记的CT1812 足够的数量和足够的质量；(目标2)进行一项开放标签的AME临床试验，在该试验中， 6名健康男性志愿者口服[14C]-CT1812，然后采集血浆、尿液和粪便进行UP 至14天，以及(目标3)分析样品以确定质量平衡恢复、PK和鉴定以及 代谢物相对丰度的量化。 CogRx的长期目标是开发CT1812作为治疗AD的潜在疾病修改疗法 治疗。由于目前尚不存在治疗AD疾病的方法，CT1812将显著促进AD的发展 医疗室。 1