Carisbamate Treatment for Alcohol Dependence

描述(由申请人提供)：尽管托吡酯没有被FDA特别批准用于这一适应症，但它是治疗酒精依赖的最有效的药物治疗之一。然而，托吡酯很少用于治疗酒精依赖，因为它有显著的副作用，包括嗜睡、头晕和认知障碍，需要逐步剂量滴定。许多患者在托吡酯帮助他们减少饮酒之前停止服用托吡酯。我们已经确定卡利斯贝酸盐是一种治疗酒精依赖的新的候选药物，因为它与托吡酯的作用机制相同，但没有托吡酯令人不安的副作用。此外，与其他抗惊厥药物不同，卡利斯贝酯和托吡酯都能减少啮齿动物的酒精摄入量。卡利斯巴酯作为癫痫的治疗方法已经过广泛的测试，是安全和耐受性良好的。药物发现德克萨斯州公司和贝勒医学院(小企业和学术申请者)正在与SK生物制药公司(专利持有人)合作，开发卡利斯贝酸盐作为酒精依赖的治疗方法并将其商业化。我们第一阶段的具体目标是进行一项人体实验室研究，以确定在使用狂犬病甲酸酯治疗期间给予轻度醉人剂量的酒精的安全性(n=20，两组各10人)。里程碑1是研究参与者能够连续四天每天耐受卡利斯氨基甲酸酯剂量(300毫克，每天2次)，没有明显的副作用，里程碑2是卡利斯甲酸酯没有过度加剧在卡利斯甲酸酯治疗期间作为挑战给予的轻度醉人剂量的酒精的影响。我们第二阶段的具体目标是完成一项双盲、随机、安慰剂对照的门诊临床试验(n=72，两组36人)。这项试验将评估卡利斯贝酯在减少接受医疗管理的寻求治疗的酒精依赖患者中重度饮酒天数的百分比方面的效果。如果这些试验证明有效，德克萨斯州药物发现公司将寻求外部资金，以支持FDA批准卡利斯氨基甲酸酯作为酒精依赖治疗所需的临床开发。

DESCRIPTION (provided by applicant): Though not specifically FDA-approved for this indication, topiramate is among the most effective medication treatments for alcohol dependence. Topiramate is rarely used to treat alcohol dependence, however, because it has prominent side effects including somnolence, dizziness, and cognitive disturbances that require gradual dose titration. Many patients stop taking topiramate before it helps them to reduce drinking. We have identified carisbamate as a new candidate treatment for alcohol dependence because it shares topiramate's mechanism of action but lacks topiramate's troubling side effects. Further, unlike other anticonvulsants, both carisbamate and topiramate reduce alcohol intake in rodents. Carisbamate has been tested extensively as a treatment for epilepsy and is safe and well tolerated. Medication Discovery Texas, Inc and Baylor College of Medicine (the Small Business and academic applicants) are collaborating with SK Biopharmaceuticals (the patent holder) to develop and commercialize carisbamate as a treatment for alcohol dependence. Our Phase I Specific Aim is to conduct a human laboratory study to determine the safety profile of administering a mildly intoxicating dose of alcohol during treatment with carisbamate (n=20, two groups of 10). Milestone 1 is that study participants are able to tolerate carisbamate dosing (300 mg bid) daily for four days without significant side effects and milestone 2 is that carisbamate did not excessively exacerbate the effects of a mildly intoxicating dose of alcohol given as a challenge during carisbamate treatment. Our Phase II Specific Aim is to complete a double-blind, randomized placebo-controlled outpatient clinical trial (n=72, two groups of 36). The trial will evaluate the efficacy of carisbamate for reducing percent heavy drinking days among treatment-seeking alcohol-dependent patients receiving medical management. If these trials demonstrate efficacy, Medication Discovery Texas will seek outside funding to support the clinical development needed for FDA approval of carisbamate as a treatment for alcohol dependence.