EVALUATION OF ADD234037 AS AN ANTI-CONVULSANT CANDIDATE

该申请的目的是确定harkoseride （ADD 2340037）是否可能是一种安全有效的癫痫治疗药物。具体来说，我们提出了两项临床研究来实现这一目标。第一个是在有限数量的患者中进行的开放标签递增剂量原理证明研究，以评估该人群的药代动力学、潜在的药物相互作用和安全性，并给出疗效指示和剂量的粗略估计。根据第一项研究获得的信息，将设计一项双盲安慰剂对照的第二项研究，以确定最佳有效剂量，并从统计学上确定harkoseride是否是一种临床有效和安全的药物。基于迄今为止的非临床疗效和作用机制研究以及临床药代动力学和耐受性研究，harkoseride已显示出独特的机制、理想的药代动力学特征和可接受的安全范围，是治疗癫痫的主要贡献。其广泛的活性范围，独特的作用机制，以及口服和肠外制剂的可用性，使其成为一种最有希望进一步开发的化合物，用于治疗现有药物无法完全控制的癫痫。

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.