RANDOMIZED DBL BLIND PLACEBO CONTR DOSE ESCALATION STUDY W/ VX 497 I

对VX-497的安全性、副作用、药物随时间进入和离开血液和组织的方式以及不同剂量的VX-497的生物活性进行评估。VX-497是一种设计用于干扰丙型肝炎病毒生长的产品。丙型肝炎病毒(丙型肝炎病毒)是黄病毒科的一种RNA病毒。丙型肝炎病毒的急性感染通常会导致轻微的、通常无症状的急性肝炎。然而，至少85%感染丙型肝炎病毒的患者没有完全清除病毒，并发展为慢性肝脏感染。一旦慢性丙型肝炎确诊，病毒的自发清除是罕见的，大多数慢性丙型肝炎患者发展为缓慢进展的肝病。在感染20年后，大多数患者有证据表明正在进行的慢性肝炎，至少20%有肝硬化(疤痕形成)。慢性丙型肝炎引起的长期问题是肝硬变、肝功能衰竭和肝癌。据估计，美国每年有8-10,000人死亡，预计未来十年还会增加。直到最近，唯一被批准的慢性丙型肝炎治疗方法是重组干扰素α和联合干扰素(Intron-A和Infergen/干扰素Alfacon-1)。VX-497是一种有效的酶抑制剂和抗病毒药物。这项研究是一项双盲、安慰剂对照的三剂量试验，每个剂量组由八名活动患者和两名安慰剂患者组成。治疗将包括三种不同剂量的研究药物。患者将接受两周的第一次注射，第二次注射两周，第三次注射四周。如果任何剂量组中的两名或两名以上患者出现与药物有关的副作用，需要终止研究，则不会升级到下一剂量组。所有患者在治疗后都将接受为期四周的随访。根据核心研究的结果，在停药四周后，患者将被允许选择继续服药三个月。

An evaluation of the safety, side effects, how a drug enters and leaves the blood and tissues over time, and the biological activity of various doses of VX-497, a product designed to interfere with the growth of the virus hepatitis C. Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family. Acute infection with HCV causes a generally mild, often asymptomatic, acute hepatitis. However, at least 85% of patients infected with HCV do not fully clear the virus and develop chronic infection of the liver. Once chronic HCV is established, spontaneous clearing of the virus is rare and the majority of patients with chronic HCV develop slowly progressive liver disease. Twenty years after infection, most patients have evidence of ongoing chronic hepatitis and at least 20% have cirrhosis (scarring). Long-term problems caused by chronic HCV are cirrhosis, liver failure, and liver cancer. There is an estimated 8-10,000 death per year in the United States and is expected to increase over the next ten years. Until recently, the only approved treatments for chronic HCV have been recombinant interferon alfa and consensus interferon (Intron-A and Infergen/interferon alfacon-1). VX-497 is a potent enzyme inhibitor and antiviral agent. This study is a double blind, placebo controlled, three-dose trial, each dose group consisting of eight active and two placebo patients. Treatment will consist of three different doses of study medication. Patients will have the first dose for two weeks, the second dose for two weeks, and the third dose for four weeks. If two or more patients in any of the dose groups experience drug-related adverse side effects requiring termination from the study, escalation to the next dose group will not occur. All patients will be followed for four weeks after the treatment. Based on the results of the core study, patients will be offered the option to continue on the medication for three more months, after a four week period off the drug.