An investigation of the effectiveness and safety of Tenofovir Disoproxil Fumarate (TDF) given on its own versus Emtricitabine and TDF taken together in patients with long lasting Hepatitis B for whom lamivudine therapy has not been successful due to the virus becoming resistant to its actio

Phase 1

Conditions: Chronic Hepatitis B
MedDRA version: 14.1Level: LLTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2008-001464-36-ES

Lead Sponsor: Gilead Sciences Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 280

Inclusion Criteria

? Chronic HBV infection, defined as positive serum HBsAg for at least 6 months
? Males and females, 18 through 75 years of age, inclusive. In Greece, only postmenopausal and/or surgically sterile women may participate.
? HBV DNA ? 10^3 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.
? Prior or current 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 ?-HCG (for females of childbearing potential only),
? Calculated creatinine clearance ? 50 mL/min
? Hemoglobin ? 10 g/dL
? Neutrophils ? 1,000 /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 239
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41

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 of reproductive potential who are not willing to use an ?effective? method of contraception during the study. This should be, at minimum, a condom.
? ALT ? 10 × ULN
? Decompensated liver disease defined as direct (conjugated) bilirubin > 1.5 x ULN, prothrombin time (PT) > 1.5 x ULN, platelets < 75,000/mm3, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage).
? Received interferon (pegylated or not) therapy within 6 months of the screening visit
? ? -fetoprotein > 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 <br>? To evaluate the biochemical and serological responses to tenofovir DF versus emtricitabine plus tenofovir DF in subjects with lamivudine resistance<br>? To compare changes in the resistance profile of each treatment arm over the duration of the study<br>? To evaluate the steady-state pharmacokinetics of tenofovir in subjects with lamivudine resistance;Primary end point(s): The primary efficacy endpoint is HBV DNA < 400 copies/mL at Week 96.;Timepoint(s) of evaluation of this end point: Week 96

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary endpoints include: HBV DNA < 169 copies/mL, HBV DNA level, ALT normal, virologic breakthrough, HBeAg/HBsAg loss and seroconversion, and development of drug resistant<br>mutations.;Timepoint(s) of evaluation of this end point: Week 96 & 240

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