phase 3 study of gsk548470 in patients with compensated chronic hepatitis b untreated with nucleic acid analogue

Conditions: Hepatitis B, Chronic

Summary: the purpose of this study is to evaluate the efficacy and safety of gsk548470 administered once daily at a dose level of 300 mg to japanese patients with compensated chronic hepatitis b untreated with any nucleic acid analogue. in efficacy, the non-inferiority of gsk548470 to etv will be verified using the antiviral effect as the index.

this study is a multicenter, randomized, active comparator-controlled, double-blind, parallel-group comparison study in japanese patients with compensated chronic hepatitis b untreated with any nucleic acid analogue and its subsequent open-label study. efficacy and safety will be compared between once-daily dosing of gsk548470 300 mg and once-daily dosing of etv 0.5 mg, and subsequently the efficacy and safety of gsk548470 administered long term will be investigated. a total of 165 subjects will be assigned to the gsk548470 group or the etv group at a ratio of 2:1. the subjects will be assigned by stratified randomization in terms of hbe antigen and serum hbv-dna level. the primary purpose is to verify the non-inferiority of gsk548470 to etv using as an index the change amount of hbv-dna level at week 24 from the baseline level. the secondary purpose is to investigate the efficacy and safety of gsk548470 300 mg administered once daily for a long term.

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 \< 480 msec with bundle branch block * chronic hbv infection, defined as positive serum hbsag for at least 6 month, or negative serum igm-hbc antibody * hbeag positive; hbv-dna \>= 6 log10 copies/ml, hbeag negative; hbv-dna \>= 5 log10 copies/ml * serum alt \>= 31 u/l and \<= 10 × uln * creatinine clearance \>= 70 ml/min * haemoglobin \>= 8 g/dl * wbc \>= 1,000 /mm3 * nucleic acid analogue naïve, i.e., no prior therapy for over 6 months in the past * no mutation that shows resistance in lam, etv and/or tdf at screening 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 nucleoside, nucleotide, 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 chronic hepatitis b