A Multi-center, Open-label Study of GSK548470 (Tenofovir Disoproxil Fumarate) in Patients With Compensated Chronic Hepatitis B With Poor Response to Other Drugs
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Number of Participants With HBV DNA Level < 2.1 log10 Copies/mL at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of once-daily treatment with GSK548470 300 mg in Japanese patients with compensated chronic hepatitis B with poor response to other drugs.
详细描述
This is a multicenter, open-label study in Japanese patients with compensated chronic hepatitis B with poor response to other drugs in order to evaluate the efficacy and safety of GSK548470 administered at a dose of 300 mg once daily. The target sample size is set at 32 subjects. The primary objective is to evaluate the efficacy and safety of once-daily treatment with GSK548470 300 mg in subjects with compensated chronic hepatitis B with poor response to other drugs. The secondary objective is to evaluate the long-term efficacy and safety of once-daily treatment with GSK548470 300 mg.To evaluate the efficacy and safety of GSK548470 in the study, subjects receiving a combination of lamivudine (LAM) and adefovir pivoxil (ADV) will be switched to a combination of LAM and GSK548470, while subjects on entecavir hydrate (ETV) with or without ADV will be switched to a combination of ETV and GSK548470.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 69 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The ability to understand and sign a written informed consent form
- •16 to 69 years of age at the time of informed consent
- •Females of childbearing potential must have a negative pregnancy test and agree to avoidance of pregnancy
- •Subject must show QTc <450 millisecond (msec) or <480msec with Bundle Branch Block
- •Chronic HBV infection, defined as positive serum HBsAg for at least 6 month
- •Subjects currently treated with LAM/ADV, ETV or ETV/ADV for greater than 24 weeks
- •Chronic hepatitis B ; HBV NDA >= 4 log10 copies/mL, Chronic hepatitis B with cirrhosis ; HBV NDA >= 3 log10 copies/mL
- •Serum ALT <= 10 × ULN
- •Creatinine clearance >= 70 mL/min
- •Haemoglobin >= 8 g/dL
- •WBC >= 1,000 /mm3
排除标准
- •Decompensated liver disease
- •Co-infection with HIV or HCV
- •Autoimmune hepatitis rather than chronic hepatitis B
- •Subject with serious complication
- •Received or have a plan for solid organ or bone marrow transplantation
- •Has proximal tubulopathy
- •History of hypersensitivity to nucleoside and/or nucleotide analogues
- •Evidence of hepatocellular carcinoma by diagnostic imaging at screening and/or serum α-fetoprotein > 50 ng/mL at screening
- •History of HCC
- •Received any interferon or HB vaccine therapy within 24 weeks prior to initiation
- •Received overdose NSAIDs, excluding temporary or topical use, within 7 days prior to initiation
- •Received drugs for injection containing glycyrrhizin as the main component within 4 weeks prior to initiation
- •Received drugs causing renal impairment, competitors of renal excretion, immunosuppressants, chemotherapeutics and/or corticosteroids within 8 weeks prior to initiation
- •Participation in another clinical study within 6 months of study entry or planned participation in another clinical study after entry to this study
- •Woman who is pregnant, lactating, possibly pregnant or planning a pregnancy during the study period
- •Psychiatry disorder or cognitive disorder that may affect the subject ability to give informed consent or to follow specified study procedures
- •History of alcohol or drug abuse
- •Any condition or situation that may interfere with the subject's participation in the study
研究组 & 干预措施
GSK548470 300 mg
GSK548470 300 mg tablet is administered orally once daily
干预措施: GSK548470 300 mg tablet (Drug)
结局指标
主要结局
Number of Participants With HBV DNA Level < 2.1 log10 Copies/mL at Week 24
时间窗: Week 24
The number of participants with serum hepatitis B virus deoxyribonucleic acid (HBV DNA) level \< the lower limit of quantitation (2.1 log10 copies/millilitres\[copies/mL\]) (i.e., the rate of suppression) at Week 24 was summarized. Statistical analysis was not provided for the number of participants achieving HBV DNA \<2.1 log10 copies/mL (at Week 24). Missing values observed during the treatment period was imputed by the last observation carried forward (LOCF) method.
次要结局
- Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants With Virological Breakthrough and Resistance-related Mutations(Screening, Week 24, Week 48, Week 96 and Virological Breakthrough)
- Mean Change From Baseline in Serum HBV DNA Level at Week 24, Week 48 and Week 96(Baseline and Week 24, Week 48 and Week 96)
- Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 48 and Week 96(Week 48 and Week 96)
- Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants Achieving Each Indicated HBcrAg Category at Baseline,Week 24, Week 48 and Week 96(Baseline, Week 24, Week 48 and Week 96)
- Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96(Baseline, Week 24, Week 48 and Week 96)