Phase 1 Safety and Pharmacokinetics of ALK001 in people over 60

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 incorporatedinto 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 overallpublic health because it seeks ways to better understand, prevent and treat macular degeneration.