http://www3.interscience.wiley.com/cgi-bin/abstract/112660914/ABSTRACTHepatology
Volume 44, Issue 1 , Pages 108 - 116
Published Online: 23 Jun 2006
A double-blind randomized trial of adefovir dipivoxil in Chinese subjects with HBeAg-positive chronic hepatitis B
MinDe Zeng 1, YiMin Mao 1 *, GuangBi Yao 2, Hao Wang 3, JinLin Hou 4, YaoZong Wang 5, Beulah N. Ji 6, Chai-Ni P. Chang 7, Keith F. Barker 6
1Renji Hospital, Shanghai, China
2Jing-An Qu Hospital, Shanghai, China
3Beijing People's Hospital, Beijing, China
4NanFang Hospital, Guangzhou, China
5Infectious Disease Hospital, Jinan, China
6GlaxoSmithKline, London, United Kingdom
7GlaxoSmithKline, Raleigh-Durham, NC
email: YiMin Mao (
mym11968@yahoo.com.cn)
*Correspondence to YiMin Mao, Renji Hospital, Shanghai, China
Potential conflict of interest: Nothing to report.
Funded by:
GlaxoSmithKline
Abstract
Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were enrolled in a multicenter, double-blind, randomized, placebo-controlled study of adefovir dipivoxil (ADV) 10 mg once daily. There was a significant difference in reduction of serum hepatitis B virus (HBV) DNA after 12 weeks between subjects who received ADV and those who received the placebo (3.4 and 0.1 log10 copies/mL, respectively, P < .001). Further reductions in serum HBV DNA and increases in the proportion of subjects with an HBV DNA level of at most 10[5] copies/mL, with HBV DNA undetectable, and with ALT normalization were observed in ADV-treated subjects at week 52 (median HBV DNA reduction of 4.5 log10 copies/mL, 67% with HBV DNA 10[5] copies/mL, 28% with HBV DNA undetectable, and 79% with ALT normalization). Subjects who initially received ADV lost some treatment benefit after being rerandomized to the placebo in week 40. Subjects with YMDD mutant HBV at baseline had virological, biochemical, and serological responses to treatment that were similar to those of subjects with wild-type HBV. The incidence of clinically adverse events was similar in nature and severity between the treatment groups, and there was no evidence of renal toxicity. No adefovir-related HBV mutations were identified. In conclusion, treatment with ADV 10 mg daily over 52 weeks was safe and effective in Chinese subjects with HBeAg-positive CHB and did not lead to the emergence of drug resistance. The study is continuing for an additional 4 years with all subjects on open-label ADV 10 mg daily. (HEPATOLOGY 2006;44:108-116.)
Received: 14 September 2005; Accepted: 8 April 2006
http://www.renji.com/list_1.asp?BigClassName=%D0%C2%CE%C5%D6%D0%D0%C4&SmallClassName=%D7%EE%D0%C2%B6%AF%CC%AC&ID=1023由我院曾民德教授和茅益民副教授负责抗乙肝新药阿德福韦酯临床研究成果在国际权威杂志《Hepatology》发表
本报讯 我院曾民德和茅益民教授负责的课题阿德福韦酯片治疗HBeAg阳性的中国慢性乙型病毒性肝炎病人52周的多中心、随机、双盲、安慰剂平行对照的临床研究成果在今年7月的国际权威杂志《Hepatology》上发表。这是国内药物多中心临床研究的成果首次在如此高影响因子的国际权威杂志上发表，该课题的研究设计、组织实施、研究中的质量控制和质量保证体系等已与国外接轨，标志了我国的药物临床研究工作已达到国际水平。
该课题以为期5年的多中心、随机、双盲、安慰剂平行对照试验，通过对480例中国慢性乙肝患者的观察，证实了核苷类抗病毒药阿德福韦酯可使患者获得病毒学、肝脏生化功能和组织学的改善。治疗52周后，HBVDNA水平较基线降低4.5 log10 拷贝/ml以上，90％以上的患者能获得HBVDNA的有效抑制，70％以上的患者ALT恢复正常；在临床上还可有效治疗YMDD变异的慢性乙肝患者；而且阿德福韦酯治疗后病毒变异发生率低，耐受性良好。
这项研究的结果提供了阿德福韦酯在我国慢性乙肝患者人群中的疗效、安全性及耐药发生情况等关键性数据,为临床合理应用该药治疗慢性乙肝提供了依据。其研究成果已获SFDA批准用于临床，直接为患者治疗提供了新的一线抗病毒药物，使患者能够得到持久的病毒抑制,减轻肝脏炎症并减少坏死,阻止疾病进展。值得一提的是，该课题的研究设计，被认为是核苷类抗病毒药临床研究的规范性设计，我国SFDA将参照该课题的设计思路，制定我国抗病毒药物临床研究的指导原则。
□消化科
