Development of A Novel Anti-Hyperglycemic Agent

描述(由申请人提供)： 我们已经在不同的动物模型和1期临床试验中证明了环二肽Cyclo(His-Pro)加锌(Cyclo-Z)治疗可以改善糖尿病的临床状况。这项研究的主要目的是证明该产品对治疗人类糖尿病安全有效。研究计划这是一项随机、双盲、安慰剂对照的平行研究。在这项研究中，我们将招募120名降糖药物NAOVE 2型糖尿病患者，并将他们随机分成4组，每组30人，以比较在12周的试验期内，含有CHP 0(安慰剂)、3 mg(最低有效)、9 mg(最佳有效)或15 mg(无额外作用)加20 mg锌的Cyclo-Z胶囊对糖尿病症状的疗效。本研究的主要结果是改善血色素A1c；次要结果是空腹血糖、餐后2小时血糖和糖耐量试验。安全性将通过出现严重不良事件(SAE)、不良事件(AEs)、生命体征的任何变化、体检、血液学、化学、肝脏、肾脏、甲状腺功能测试、尿液分析以及锌、铜水平进行评估。 公共卫生相关性： 与退伍军人健康相关糖尿病是一种困难且具有挑战性的慢性疾病，是美国第七大死因(61例)。退伍军人管理局在163个医疗中心为全国约500万名患者提供医疗服务，糖尿病在退伍军人管理局患者中的患病率很高。2000年，19.6%的VA患者患有糖尿病，这一比例以每年2%的速度增长(61)。因此，退伍军人管理局患者中的糖尿病人口在2008年可能接近30%。退伍军人医学中心约30%的药房处方是由糖尿病患者开的(62)，2000年总体23%的药房支出与患者的血糖控制有关。1998年的门诊开支为2.148亿元，住院开支为14.5亿元(63)。Cyclo-Z可能会让30%以上的退伍军人受益。这种新药可能会改善糖尿病，减少胰岛素抵抗，从而大大降低住院和门诊医疗服务的成本以及药房费用。DVA现在拥有Cyclo-Z治疗糖尿病、肥胖症和阿尔茨海默病的三项不同专利，并已完成第一阶段临床试验，取得了良好的结果。拟议的2a期临床试验的结果将导致DVA与一家主要制药公司就Cyclo-Z的营销达成协议。我们相信，Cyclo-Z在预防和治疗糖尿病方面将是有效和安全的，这种新药将有利于许多糖尿病退伍军人的健康。

DESCRIPTION (provided by applicant): We have demonstrated that a cyclic dipeptide Cyclo (his-pro) plus zinc (Cyclo-Z) treatment improved clinical conditions of diabetes in various animal models and a phase 1 clinical trial. The main objective of this study is to demonstrate that this product is safe and effective for the treatment of human diabetes. Research Plan This is a randomized, double blinded, placebo-controlled, and parallel study. In this study, we will recruit 120 hypoglycemic drug naove type 2 diabetic patients and randomize them into 4 groups of 30 subjects each to compare the effects of a Cyclo-Z capsule containing CHP 0 (placebo), 3 mg (minimally effective), 9 mg (optimally effective), or 15 mg (no-additional effect) plus 20 mg zinc on diabetic symptoms in a 12-week trial period. The primary outcome of this study is improvement of hemoglubin A1c; secondary outcomes are fasting blood glucose, 2 hours postprandial glucose and glucose tolerance test. Safety will be assessed by the presence of severe adverse events (SAEs), adverse events (AEs), any changes of vital signs, physical exams, blood hematology, chemistry, liver, renal, thyroid function tests, urine analysis and zinc, copper levels. PUBLIC HEALTH RELEVANCE: Relevance to the Veterans Health Diabetes is a difficult and challenging chronic disease, and the seventh leading cause of death in the US (61). The DVA provides healthcare service to about 5.0 million patients throughout the country in 163 medical centers, and diabetes has high prevalence in VA patients. In the year 2000, 19.6% of VA patients had diabetes and this percentage increases annually by 2 % (61). Hence, the diabetic population among VA patients may approach 30% in the year 2008. About 30 % of pharmacy prescriptions of the VA Medical Centers are received by diabetic patients (62) and overall 23 % of pharmacy expenditures were related to patients' glycemic control in the year 2000. The expenditure for the outpatient visits was $214.8 million and inpatient expenditure was $1.45 billion in 1998 (63). Cyclo-Z may pose a benefit to more than 30% of veteran population. This new drug may ameliorate diabetes and reduce insulin-resistance which would greatly reduce the cost of inpatient and outpatient medical service as well as pharmacy expenditure. Three different patents with Cyclo-Z for the treatment of diabetes, obesity and Alzheimer's disease are now owned by the DVA and the phase 1 clinical trial has been completeds with favorable result. The outcome of the proposed phase 2a clinical trial will lead to an agreement with a major drug company by the DVA for Cyclo-Z marketing. We believe that Cyclo-Z will be effective and safe in the prevention and treatment of diabetes and that this novel drug will be beneficial to the health of many diabetic veteran patients.