Phase 1 Safety and Pharmacokinetics of ALK001 in people over 60

描述（由申请人提供）：Alkeus Pharmaceuticals和哥伦比亚大学医学中心之间的这项合作研究的总体目标是评估一种新的用于干性年龄相关性黄斑变性（干性AMD）的口服研究性治疗，干性AMD是美国失明的主要原因，和Stargardt病，也称为青少年黄斑变性。研究化合物是富含氘的维生素A，D3-维生素A。D3-维生素A减缓眼睛中毒性维生素A二聚体和脂褐质的形成，从而在干性AMD/ Stargardt病的动物模型中保持视觉功能。这项研究的主要假设是，延缓维生素A二聚化也将减缓脂褐素积累和干性AMD和Stargardt病的病程。这项资助的主要目的是完成D3-维生素A的安全性评估，以便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FDA批准（开放IND）。我们将通过完成以下具体目标来实现这一目标。目的：完成为期一个月（1周给药）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和3 mg/天是安全的，无需进一步研究。2)在给予维生素A后，血液中D3-维生素A与总非氘代维生素A的比率随时间增加。方法：采用标准血肝酶、血脂、尿常规及血浆D3-维生素A测定。总持续时间：6个月（从首例患者筛选至报告发表） 公共卫生相关性：这项拟议的研究与整体公共卫生有关，因为它寻求更好地理解、预防和治疗黄斑变性的方法。

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.