Zonisamide for Weight Reduction in Obese Adults

描述（由申请人提供）：美国的肥胖患病率已上升到流行病的比例。药物治疗适用于体重指数（BMI）≥ 30 kg/m2以及BMI ≥ 27 kg/m2且存在共病风险因素的患者的体重减轻。然而，目前用于减轻体重的药物治疗选择很少，并且由于缺乏疗效、副作用或禁忌症，可用的治疗未能为许多肥胖患者提供足够的益处。因此，非常需要开发新的治疗方法来管理肥胖症。 唑尼沙胺，一种目前作为抗癫痫药上市的药物，在我们小组进行的一项为期16周的初步研究中，已被证明能促进肥胖患者的体重显著减轻。然而，在美国拥有唑尼沙胺独家营销权的制药公司将不会在更大的患者样本中进行更长时间的进一步研究以寻求新的适应症，因为该药物的市场独占权将在不到两年的时间内到期。 由于唑尼沙胺可以成为我们对抗肥胖的潜在武器，我们希望通过一项为期一年的随机临床试验来进一步研究这种药物的疗效。由于我们的初步试验设计不允许我们评估较小剂量的唑尼沙胺是否也可能有效，因此我们将在本研究中检查剂量反应以及长期疗效和安全性评估。我们还将系统地评估唑尼沙胺治疗实现的体重减轻是否可以减少代谢和心血管风险因素。

DESCRIPTION (provided by applicant): Obesity prevalence in the US has risen to epidemic proportions. Pharmacotherapy is indicated for weight reduction in patients with body mass index (BMI) >=30 kg/m 2 as well as those with BMI >=27 kg/m 2 in the presence of co-morbid risk factors. However, currently there are very few pharmacologic treatment options for weight reduction, and the available treatments fail to provide adequate benefit for many obese patients because of lack of efficacy, side effects, or contraindications. Hence, there is considerable need for developing new treatments for the management of obesity. Zonisamide, a drug that is currently marketed as an antiepileptic, has been shown to promote significant weight loss in obese patients in a 16-week preliminary investigation conducted by our group. However, the pharmaceutical company that has exclusive marketing rights for zonisamide in the US will not conduct further studies of longer duration with a larger sample of patients to seek a new indication, as the market exclusivity on this drug is due to expire in less than two years. Because Zonisamide can be a potential weapon in our fight against obesity, we wish to pursue this idea further via a randomised clinical trial examining the efficacy of the drug over a year. Since our preliminary trial design did not allow us to assess whether a smaller dose of zonisamide might also be effective, we will examine dose-response in this study in addition to assessment of long-term efficacy and safety. We will also systematically assess whether weight loss achieved with zonisamide treatment can reduce metabolic and cardiovascular risk factors.