PHASE II SEQUENTIAL COHORT 3 DOSE LEVELS OF ORAL ADEFOVIR DIPIVOXIL

慢性乙型肝炎病毒(HBV)仍然是全球范围内的重要疾病 发病原因、死亡原因和潜在新感染的来源。 据估计，全球有3亿乙肝病毒携带者。 干扰素α-2b是唯一被批准用于治疗慢性粒细胞白血病的药物 慢性乙肝病毒。对病毒的长期抑制只是完成了 在25%-50%的接受干扰素的人中。此外，许多人无法 因为副作用而无法忍受这种药物。因此，有效和 需要安全的治疗乙肝感染的新药物。 阿德福韦(PNMA或9-[2-(膦甲氧基)乙基]腺嘌呤)是一种广谱的 具有体外和体内抗肿瘤活性的光谱核苷酸类似物 肝炎病毒、逆转录病毒和疱疹病毒。它也有活动 抗鸭和人乙肝病毒的体外和动物实验 模特们。阿德福韦酯，也被称为BIS-POM PMEA；是一种口服 阿德福韦(PMEA)的可用前药。在DHBV型感染模型中， 阿德福韦被发现在肝脏和肝外部位都有活性， 如胆管和胰腺，随着D乙肝标志物的减少。 每天给15名乙肝病毒感染者服用120毫克 在四周的时间里，阿德福韦酯与快速和 血清HBVdna水平显著下降。肝脏中的隆起 在接受活性药物治疗的参与者中发现了转氨酶。之后 终止服药后，HBVDNA水平在接下来的几天内恢复到基线水平 在活跃的吸毒者中呆了六周。 由于在最初的试验中观察到了强大的抗病毒活性， 建议对该药物在慢性乙肝患者中的应用进行进一步研究。 作为多中心试验的一部分，我们计划研究阿德福韦酯，网址为 在先前评估的剂量基础上再降低剂量(30、60毫克/天) (每天120毫克)。受试者将按顺序每天接受药物治疗12周 进一步评价其安全性、耐受性和抗HV活性。 阿德福韦酯。

Chronic hepatitis B virus (HBV) continues to be an important worldwide cause of morbidity, mortality and source of potential new infections. There are estimated to be 300 million carriers of HBV in the world. Interferon alpha-2b is the only drug approved for the treatment of chronic HBV. Long term suppression of virus has only been accomplished in 25-50% of people receiving interferon. Furthermore many are unable to tolerate the drug because of side effects. Therefore effective and safe new agents for the treatment of hepatitis B infection are needed. Adefovir (PNMA or 9-[2-(phosphonomethoxy)ethyl]adenine) is a broad spectrum nucleotide analog with in vitro and in vivo activity against hepadnaviruses, retroviruses, and herpesviruses. It also has activity against duck (DHBV) and human hepatitis B (HBV) in vitro and in animal models. Adefovir dipivoxil, also known as bis-POM PMEA; is an orally available prodrug of adefovir (PMEA). In the DHBV model of infection, adefovir was found to be active in both hepatic and extrahepatic sites, such as bile ducts and the pancreas, with reductions in DHBV markers. When administered at a daily dose of 120 mg to 15 HBV-infected people for four weeks, adefovir dipivoxil was associated with rapid and significant declines in serum HBV DNA levels. Elevations in liver transaminases were noted in participants receiving active drug. After termination of dosing, HBV DNA levels returned to baseline over on to six weeks in active drug recipients. Due to the potent antiviral activity observed in this initial trial, further study of this drug in patients with chronic HBV is proposed. As part of a multicenter trial, we plan to study adefovir dipivoxil at lower doses (30, 60 mg/day) in addition to the dose previously evaluated (120 mg/day). Subjects will receive drug daily for 12 weeks in order to further evaluate the safety, tolerance and anti-HV activity of adefovir dipivoxil.