Entecavir Plus Adefovir Combination Therapy Versus Entecavir Monotherapy vs Therapy With Adefovir Plus Lamivudine for Chronic Hepatitis B Infected Subjects With Lamivudine-resistant Virus
Condition: Hepatitis B, Chronic
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: Entecavir; Tenofovir; Adefovir; Lamivudine
Intervention description: Tablets, Oral, 1mg, once daily, 100 weeks; Tablets, Oral, 300 mg, once daily; Tablets, Oral, 10mg, once daily, 100 weeks; Tablets, Oral, 100mg, once daily, 100 weeks
Intervention MeSH terms: Tenofovir; Lamivudine; Entecavir; Adefovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 629.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir
      combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine
    

Eligibility criteria:

        Inclusion Criteria:

          -  Evidence of lamivudine (LVD) resistance

          -  Subjects must have a history of previous LVD treatment at screening, and must have
             evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at
             reverse transcriptase codon 204 (M204V/I/S)

          -  Nucleoside- and nucleotide-naive, except for LVD, and had chronic hepatitis B (HBV)
             infection

          -  Compensated liver function and must have met ALL of the following
             criteria:International normalization ratio (INR) ≤ 1.5; Serum albumin ≥ 3 g/dL (≥ 30
             g/L); Serum total bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L)

          -  HBV DNA > 1.72 x 10*4* IU/mL (approximately 10*5* copies/mL)

          -  Documentation of hepatitis B e antigen (HBeAg) positive and hepatitis B e antibody
             (HBeAb) negative status at screening

          -  alanine aminotransferase (ALT) ≤ 10 * upper limit of normal (ULN) at screening

          -  Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the
             last dose of investigational product) in such a manner that the risk of pregnancy is
             minimized

          -  WOCBP include any female who has experienced menarche and who has not undergone
             successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral
             oophorectomy) or is not postmenopausal. Post menopausal is defined as:

          -  Women who are using oral contraceptives, other hormonal contraceptives (vaginal
             products, skin patches, or implanted or injectable products), or mechanical products
             such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to
             prevent pregnancy, or are practicing abstinence or where partner is sterile (e.g.,
             vasectomy), should be considered to be of child bearing potential

          -  WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
             or equivalent units of human chorionic gonadotropin) within 72 hours prior to the
             start of investigational product

        Exclusion Criteria:

          -  Evidence of decompensated cirrhosis

          -  Coinfection with human immunodeficiency virus, hepatitis C virus , or hepatitis D
             virus

          -  Women who are pregnant or breastfeeding

          -  Sexually active fertile men not using effective birth control if their partners were
             WOCBP

          -  Laboratory values out of protocol-specified range