Phase 1 Safety and Pharmacokinetics of ALK001 in people over 60

ALK001 在 60 岁以上人群中的 1 期安全性和药代动力学

• 批准号: 8252282
• 负责人: ILYAS WASHINGTON
• 金额: $ 16.52万
• 依托单位: ALKEUS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8252282
• 关键词: Academic Medical Centers; Adolescent; Affect; Age related macular degeneration; Age-Years; Animal Model; Attention; Blindness; Blood; Carbon; Child; Clinical; Clinical Research; Clinical Trials; Deuterium; Dimerization; Disease; Dose; Drug Kinetics; Elderly; Enzymes; Evaluation; Eye; FDA approved; Genes; Goals; Grant; Human; Hydrogen; Hydrogen Bonding; Impairment; Investigation; Investigational Therapies; Isotopes; Legal patent; Lipofuscin; Liver; Low Prevalence; Macular degeneration; Marketing; Measures; Metabolism; Methods; Modification; Mutation; Neutrons; Nonexudative age-related macular degeneration; Oral; Orphan; Outcome; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pigment Epithelium of Eye; Plasma; Pregnant Women; Process; Property; Proteins; Public Health; Publications; Questionnaires; Reaction; Reporting; Research; Retinal Diseases; Risk; Safety; Screening procedure; Serum; Side; Staging; Stargardt' s disease; Structure of retinal pigment epithelium; Testing; Time; Toxic effect; United States; Urine; Vision; Vitamin A; Vitamins; Work; absorption; blood lipid; chemical reaction; compound eye; design; dimer; efficacy trial; experience; novel; open label; premature; prevent; response

DESCRIPTION (provided by applicant): The overall goal of this collaborative research between Alkeus Pharmaceuticals and Columbia University Medical Center is to evaluate a new oral investigational treatment for dry age-related macular degeneration (dry-AMD), the leading cause of blindness in the U.S., and Stargardt's disease, also known as juvenile macular degeneration. The investigational compound is a vitamin A enriched with deuterium, D3-vitamin A. D3-vitamin A slows formation of toxic vitamin A dimers and lipofuscin in the eye, resulting in preserved visual function in the animal models of dry-AMD/ Stargardt's disease. The main hypothesis of this research is that retarding vitamin A dimerization will also slow lipofuscin accumulation and the course of dry-AMD and Stargardt's disease. The primary objective of this grant is to complete a safety evaluation of D3-Vitamin A so that a larger efficacy trial for dry-AMD can be conducted. This safety trial has already been approved by the FDA (open IND). We will achieve this objective by completing the following specific aim. Aim: Complete a one-month (1 week dosing) open label clinical trial to assess the safety of D3- vitamin A and determine whether safe but significant levels of D3-vitamin A can be incorporated into the blood in patents over 60 years of age. Outcome: 1) D3-vitamin A at 1.5 and 3 mg/day is safe, warranting further investigation. 2) Ratio of D3-vitamin A over total non deuterated vitamin A in the blood increases over time upon dosing with vitamin A. Methods: Follow standard blood liver enzymes, blood lipids, urine analysis and plasma D3-vitamin A. Total Duration: 6 months (from first patient screening to report publication) PUBLIC HEALTH RELEVANCE: The proposed research is relevant to overall public health because it seeks ways to better understand, prevent and treat macular degeneration.

描述(申请人提供)：Alkeus制药公司和哥伦比亚大学医学中心的这项合作研究的总体目标是评估一种新的口服研究疗法，用于治疗干性老年性黄斑变性(Dry-AMD)和Stargardt病(也称为青少年黄斑变性)。干性老年性黄斑变性是美国的主要失明原因。研究化合物是一种富含氘的维生素A，D3-维生素A。D3-维生素A减缓眼睛中有毒维生素A二聚体和脂褐素的形成，从而在干性AMD/Stargardt病的动物模型中保留视觉功能。这项研究的主要假设是，延缓维生素A二聚化也会减缓脂褐素的积累，减缓干性AMD和Stargardt病的病程。这笔赠款的主要目标是完成D3-维生素A的安全性评估，以便能够进行更大规模的干性AMD疗效试验。这项安全性试验已经获得了FDA(Open Ind)的批准。我们将通过完成以下具体目标来实现这一目标。目的：完成一项为期一个月(一周剂量)的开放标签临床试验，以评估D3-维生素A的安全性，并确定是否可以将安全但显著水平的D3-维生素A纳入60岁以上患者的血液中。结果：1)D3-维生素A 1.5 mg/d和3 mg/d是安全的，值得进一步研究。2)服用维生素A后，血液中D3-维生素A占总非氚维生素A的比例随着时间的推移而增加。方法：遵循标准的血液肝酶、血脂、尿液分析和血浆D3-维生素A。总时间：6个月(从第一个患者筛查到报告发表) 公共卫生相关性：拟议的研究与整体公共健康相关，因为它寻求更好地了解、预防和治疗黄斑变性的方法。