Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B With Poor Response to Other Drugs

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* 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

Exclusion Criteria:

* 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