phase 3 study of gsk548470 in patients with compensated chronic hepatitis b with poor response to other drugs

Conditions: Hepatitis B, Chronic

Summary: 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

Keywords: tenofovir disoproxil fumarate, compensated chronic hepatitis b