Carisbamate Treatment for Alcohol Dependence

描述（由申请人提供）：虽然没有专门FDA批准用于此适应症，托吡酯是最有效的药物治疗酒精依赖。然而，托吡酯很少用于治疗酒精依赖，因为它具有显著的副作用，包括嗜睡、头晕和认知障碍，需要逐渐调整剂量。许多患者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carisbamate作为一种新的候选治疗酒精依赖，因为它共享托吡酯的行动机制，但没有托吡酯的令人不安的副作用。此外，与其他抗惊厥药不同，carisbamate和托吡酯都能减少啮齿动物的酒精摄入。Carisbamate已被广泛测试作为癫痫的治疗，是安全和耐受性良好的。药物发现得克萨斯州公司和贝勒医学院（小企业和学术申请人）正在与SK生物制药公司（专利保持器）合作，开发和商业化carisbamate作为酒精依赖的治疗。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特征（n=20，两组，每组10人）。里程碑1是研究受试者能够耐受卡立氨酯每日给药（300 mg bid），持续4天，无显著副作用，里程碑2是卡立氨酯治疗期间作为挑战给予的轻度中毒剂量酒精的作用未过度加重。我们的II期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=72，两组各36例）。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疗效。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.