EVALUATION OF ADD234037 AS AN ANTI-CONVULSANT CANDIDATE

本申请的目的是确定哈可色胺(ADD 2340037)是否是一种潜在的安全有效的癫痫治疗方法。具体地说，提出了两项临床研究来实现这一目标。第一项是在有限数量的患者中进行的开放式递增剂量原则研究，以评估该人群中的药代动力学、潜在的药物相互作用和安全性，并给出疗效的指示和剂量的粗略估计。根据第一项研究中获得的信息，将设计一项双盲安慰剂对照第二项研究，以确定最佳、有效的剂量，并从统计学上确定哈可色胺是否为临床有效和安全的药物。根据迄今为止的非临床药效和作用机制研究以及临床药代动力学和耐受性研究，哈可色胺已经显示出独特的机制、理想的药代动力学曲线和可接受的安全裕度，是治疗癫痫的主要贡献。拟议的商业应用哈可色胺(ADD 234037)在非临床和临床研究中显示出极好的安全性、有效性和药代动力学曲线。其广泛的活性梯度、独特的作用机制(S)以及口服和非肠道制剂的可获得性使其成为进一步开发用于治疗癫痫的最有希望的化合物，现有药物无法完全控制癫痫。

The objective of this application is to determine whether harkoseride (ADD 2340037) is potentially a safe and effective treatment for epilepsy. Specifically, two clinical studies are proposed to achieve this objective. The first is an open-label ascending dose proof of principle study in a limited number of patients to assess pharmacokinetics, potential drug interactions, and safety in this population and to give an indication of efficacy and a rough estimate of dose. From the information gained in this first study, a double blind placebo controlled second study will be designed to establish an optimal, effective dose and to statistically determine whether harkoseride is a clinically effective and safe agent. Based on nonclinical efficacy and mechanism of action studies and clinical pharmacokinetic and tolerability studies to date, harkoseride has demonstrated a unique mechanism, an ideal pharmacokinetic profile, and acceptable safety margin to be a major contribution to the treatment of epilepsy, PROPOSED COMMERCIAL APPLICATION Harkoseride (ADD 234037) has demonstrated an excellent safety, efficacy, and pharmacokinetic profile in nonclinical and clinical studies. Its broad ramp of activity, unique mechanism(s) of action, and availability of both an oral and parenteral formulation make a most promising compound for further development to treat epilepsy, a disease which is not completely controlled with existing medication.