Tenofovir Disoproxil Fumarate (Tenofovir DF) Versus Emtricitabine/Tenofovir DF in Subjects Resistant to Lamivudine
| Status: | Completed |
|---|---|
| Conditions: | Hepatitis, Hepatitis |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 4/21/2016 |
| Start Date: | September 2008 |
| End Date: | February 2015 |
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
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.
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.
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
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