A Phase 3b, Randomized, Double-Blind, Double-Dummy Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects With Chronic Hepatitis B Who Are Resistant to Lamivudine
TDF
+ FTC/TDF Placebo
+ FTC/TDF
Blood-Borne Infections+12
+ Communicable Diseases
+ Digestive System Diseases
Treatment Study
Summary
Study start date: September 1, 2008
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.280 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 75 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.2 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives