Tenofovir Disoproxil Fumarate (Tenofovir DF) Versus Emtricitabine/Tenofovir DF in Subjects Resistant to Lamivudine
- Conditions
- Hepatitis B
- Interventions
- Registration Number
- NCT00737568
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 280
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tenofovir DF TDF TDF plus placebo to match FTC/TDF Tenofovir DF FTC/TDF Placebo TDF plus placebo to match FTC/TDF FTC/TDF FTC/TDF FTC/TDF plus placebo to match TDF FTC/TDF TDF Placebo FTC/TDF plus placebo to match TDF
- Primary Outcome Measures
Name Time Method Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96 Week 96
- Secondary Outcome Measures
Name Time Method Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 Baseline; Weeks 48, 96, 144, 192, and 240 The percentage of participants who were HBeAg positive at baseline and who had HBeAg Loss at the given time point was summarized. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative.
HBV DNA Level at Weeks 48, 96, 144, 192, and 240 Weeks 48, 96, 144, 192, and 240 Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 Weeks 48, 96, 144, 192, and 240 Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 Weeks 48, 144, 192, and 240 Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 Baseline; Weeks 48, 96, 144, 192, and 240 The percentage of participants who were HBeAg positive at baseline and who had seroconversion to anti-HBe at the given time point was summarized. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive.
Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 Baseline; Weeks 48, 96, 144, 192, and 240 The percentage of participants with HBsAg Loss at the given time point was summarized. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.
Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 Baseline; Weeks 48, 96, 144, 192, and 240 The percentage of participants with seroconversion to anti-HBs at the given time point was summarized. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.
Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 Baseline; Weeks 48, 96, 144, 192, and 240 The percentage of participants with virologic breakthrough at the given time point was summarized. Virologic breakthrough was defined as having two consecutive 1.0 log10 or greater increases in serum HBV DNA from on-treatment nadir, or two consecutive HBV DNA values ≥ 400 copies/mL after being \< 400 copies/mL.
Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240 BMD is calculated as grams per cubic centimeter (g/cm\^2); the mean (SD) percentage change is presented.
Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240 BMD is calculated as g/cm\^2; the mean (SD) percentage change is presented.
Development of Drug-resistant Mutations (DRMs) Baseline to Week 240 The development of DRMs was summarized, either as development of new DRMs or enrichment of existing DRMs.
Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 Weeks 48, 96, 144, 192, and 240 Normal ALT was defined as having a value less than or equal to the ULN. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.