Tenofovir Disoproxil Fumarate (Tenofovir DF) Versus Emtricitabine/Tenofovir DF in Subjects Resistant to Lamivudine
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Intervention: TDF; FTC/TDF; TDF Placebo; FTC/TDF Placebo
Intervention description: Tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg tablet administered orally once daily; Emtricitabine (FTC)/TDF 200/300 mg fixed-dose combination tablet administered orally once daily; TDF placebo tablet administered orally once daily; FTC/TDF placebo tablet administered orally once daily
Intervention MeSH terms: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 280.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Tenofovir DF; Emtricitabine; Chronic hepatitis B; Combination therapy

Summary:

      The aim of therapy for the treatment of chronic hepatitis B virus (HBV) is to maintain
      suppression of viral replication to prevent the emergence of complications, which requires
      long-term therapy. Durable suppression of viral replication is achieved in the treatment of
      chronic viral diseases by preventing of the emergence of drug-resistant mutations. The
      clinical guidelines for the management of lamivudine resistant patients are variable. Some
      recommend switching to another agent without cross-resistance, while others recommend adding
      on another agent without cross-resistance. Limited clinical data exists to demonstrate
      whether tenofovir disoproxil fumarate (tenofovir DF; TDF) is an effective monotherapy for
      lamivudine resistant patients or if it should be used as part of a combination therapy
      regimen.

      This study is designed to evaluate the effectiveness, safety, and tolerability of tenofovir
      DF monotherapy versus emtricitabine (FTC)/tenofovir DF combination therapy in participants
      with chronic HBV with lamivudine resistance (presence of the rtM204I/V mutation with or
      without the rtL180M mutation) over a 240-week period. Participants in this study must be
      receiving lamivudine treatment at the time of enrollment.
    

Eligibility criteria:

        Inclusion Criteria

          -  Chronic HBV infection, defined as positive serum HBsAg for at least 6 months

          -  18 through 75 years of age, inclusive

          -  HBV DNA ≥ 10^3 IU/mL

          -  Receiving treatment with lamivudine with confirmation of HBV reverse transcriptase
             mutation(s) known to confer resistance to lamivudine (rtM204I/V with or without
             rtL180M) by central laboratory assessment prior to randomization; adefovir dipivoxil
             treatment of ≤ 48 weeks at the time of screening (inclusive of combination adefovir
             dipivoxil + lamivudine at entry) was allowed

          -  Willing and able to provide written informed consent

          -  Negative serum pregnancy test (for females of childbearing potential only)

          -  Calculated creatinine clearance ≥ 50 mL/min

          -  Hemoglobin ≥ 10 g/dL

          -  Neutrophils ≥ 1000 /mm^3

          -  No prior oral HBV therapy with approved nucleotide and/or nucleoside therapy or other
             investigational agents for HBV infection other than lamivudine or adefovir dipivoxil

        Exclusion Criteria

          -  Pregnant women, women who are breast feeding or who believe they may wish to become
             pregnant during the course of the study

          -  Males and females of reproductive potential who are not willing to use an effective
             method of contraception during the study

          -  Alanine aminotransferase (ALT) ≥ 10 × the upper limit of the normal range (ULN)

          -  Decompensated liver disease

          -  Interferon or pegylated interferon therapy within 6 months of the screening visit

          -  Alpha fetoprotein > 50 ng/mL

          -  Evidence of hepatocellular carcinoma

          -  Coinfection with hepatitis C virus, HIV, or hepatitis D virus

          -  Significant renal, cardiovascular, pulmonary, or neurological disease

          -  Received solid organ or bone marrow transplantation

          -  Receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational
             agents, nephrotoxic agents, or agents susceptible of modifying renal excretion

          -  Proximal tubulopathy

          -  Known hypersensitivity to the study drugs, the metabolites or formulation excipients