Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue
Condition: Hepatitis B, Chronic
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: GSK548470 300 mg tablet; ETV 0.5 mg capsule
Intervention description: Blue tablets, each tablet containing 300 mg of tenofovir disoproxil fumarate; Brown capsules, each capsule containing 0.53 mg of entecavir hydrate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 166.0
Sex: All
Minimum age: 16 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: Tenofovir Disoproxil Fumarate; Chronic Hepatitis B

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.
    

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