Carisbamate Treatment for Alcohol Dependence

描述（由申请人提供）：托吡酯是治疗酒精依赖最有效的药物之一，虽然fda没有特别批准这种适应症。然而，托吡酯很少用于治疗酒精依赖，因为它有明显的副作用，包括嗜睡、头晕和认知障碍，需要逐渐剂量滴定。许多病人在托吡酯帮助他们减少饮酒之前就停止服用。我们已经确定了氨基甲酸酯作为酒精依赖的新候选治疗方法，因为它具有托吡酯的作用机制，但没有托吡酯令人不安的副作用。此外，与其他抗惊厥药不同，carisbamate和topiramate都能减少啮齿动物的酒精摄入量。Carisbamate作为一种治疗癫痫的药物已经进行了广泛的测试，并且安全且耐受性良好。药物发现德克萨斯公司和贝勒医学院（中小企业和学术申请者）与SK生物制药（专利持有人）合作，开发用于治疗酒精依赖的carisbamate并将其商业化。我们的I期具体目标是进行一项人体实验室研究，以确定在carisbamate治疗期间给予轻度中毒剂量的酒精的安全性（n=20，两组10人）。里程碑1是研究参与者能够耐受carisbamate剂量（300 mg bid），连续4天没有明显的副作用，里程碑2是carisbamate没有过度加剧在carisbamate治疗期间给予轻度中毒剂量的酒精的影响。我们的II期具体目标是完成一项双盲，随机安慰剂对照门诊临床试验（n=72，两组36）。该试验将评估carisbamate在接受医疗管理的寻求治疗的酒精依赖患者中减少重度饮酒天数百分比的功效。如果这些试验证明有效，德克萨斯药物发现公司将寻求外部资金支持FDA批准carisbamate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.