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
- Conditions
- Chronic Hepatitis BMedDRA version: 14.1Level: LLTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2008-001464-36-CZ
- Lead Sponsor
- Gilead Sciences Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
• 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 ß-HCG (for females of childbearing potential only), although in
Greece only post-menopausal and/or surgically sterile women may participate.
• 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
• 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. In Greece, only postmenopausal and/or surgically sterile women may participate.
• 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
• a -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 <br>;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