Chronic Hepatitis B MedDRA version: 9.1 Level: LLT Classification code 10008910 Term: Chronic hepatitis B
Conditions
Interventions
Trade Name: Viread
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tenofovir disoproxil fumarate
CAS Number: 52232-67-4
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
Gilead Science Incorporated
Eligibility
Sex/Gender
All
Inclusion 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 = 10^4 copies/mL • Currently receiving 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) is allowed • Willing and able to provide written informed consent • Negative serum ß-HCG (for females of childbearing potential only) • Calculated creatinine clearance = 50 mL/min • Hemoglobin = 10 g/dL • Neutrophils = 1,500 /mm3 • 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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. For males, condoms should be used and for females, a barrier contraception method should be used in combination with one other form of contraception. • ALT = 10 × ULN • Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, prothrombin time (PT) > 1.2 x ULN, platelets 50 ng/mL • Evidence of HCC • Co infection with HCV (by serology), HIV, or HDV • Significant renal, cardiovascular, pulmonary, or neurological disease • Received solid organ or bone marrow transplantation • Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion • Has proximal tubulopathy • Known hypersensitivity to the study drugs, the metabolites or formulation excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare the antiviral efficacy against hepatitis B virus (HBV) of once-daily tenofovir DF versus once-daily emtricitabine plus tenofovir DF combination treatment in subjects with lamivudine resistance;Secondary Objective: • To evaluate the safety and tolerability of tenofovir DF versus emtricitabine plus tenofovir DF combination treatment in subjects with lamivudine resistance • To evaluate the biochemical and serological responses to tenofovir DF versus emtricitabine plus tenofovir DF in subjects with lamivudine resistance • To compare changes in the resistance profile of each treatment arm over the duration of the study • To evaluate the steady-state pharmacokinetics of tenofovir in subjects with lamivudine resistance ;Primary end point(s): The primary endpoint is HBV DNA < 400 copies/mL at Week 48 (and every 48 weeks thereafter, due to group sequential testing for the primary efficacy analysis). A “persistent virologic response” approach to handling missing data will be employed; the details of this convention will be included in a separate statistical analysis plan | — |
Countries
Austria, Bulgaria, Czech Republic, Germany, Hungary, Spain, United Kingdom
Outcome results
None listed