Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B
- Conditions
- Chronic Hepatitis BHepatitis B
- Interventions
- Registration Number
- NCT00412529
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This exploratory study is designed to determine the early viral kinetic profile during treatment with telbivudine or entecavir at multiple time points over 12 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
- Male or female, 18-70 years of age with documented compensated hepatitis B "e" antigen (HBeAg)-positive chronic hepatitis B
- Able to comply with study regimen and provide written informed consent
- Pregnant or breastfeeding
- Unwilling to use double barrier method of contraception
- Co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
- Received Hepatitis B therapy in the past
- Use of immunomodulatory therapy in past 12 months
- History of or symptoms of hepatic decompensation or pancreatitis
- Frequent or prolonged use of potentially hepatotoxic or nephrotoxic drugs
- Concurrent medication likely to preclude compliance with schedule of evaluations
- Use of other investigational drugs within 30 days of enrollment
- Abnormal laboratory values during screening
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Telbivudine Telbivudine - Entecavir Entecavir -
- Primary Outcome Measures
Name Time Method Change in Mean Hepatitis B Virus (HBV) DNA Levels Baseline (day 1) to Week 12 (day 85) Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.
- Secondary Outcome Measures
Name Time Method Change in Alanine Aminotransferase (ALT) Levels From Baseline to Week 12 Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance Baseline to 12 weeks Viral kinetic parameters were estimated with a bi-phasic mathematical model:
V(t) = (1-ε)pI(t) - cV(t)
I(t) = (1- η)TV(t) - δI(t)
V serum viral load, I productively infected cells, ε efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, η efficiency factor of blocking de novo infection, β de novo infection rate, T uninfected target cells, δ rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data.Change in Mean HBV DNA Level Baseline (day 1) to Weeks 2, 4, 8 Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.HBV DNA reductions, considered as the repeated measures, from baseline to Weeks 2, 4, 8.
The Area Under the Curve (AUC) of HBV DNA Change. From Baseline to Week 12 In AUC efficacy analyses, all the visits from baseline to Week 12 visit (including the planned and the repeated) with a non-missing HBV DNA level were included.
Characterization of Very Early Viral Kinetics: Estimation of the Rate of Infected Cell Loss Baseline to 12 weeks Viral kinetic parameters were estimated with a bi-phasic mathematical model:
V(t) = (1-ε)pI(t) - cV(t)
I(t) = (1- η)TV(t) - δI(t)
V serum viral load, I productively infected cells, ε efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, η efficiency factor of blocking de novo infection, β de novo infection rate, T uninfected target cells, δ rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data.Characterization of Very Early Viral Kinetics: Estimation of the Efficiency Factor of Blocking Virus Production Baseline to 12 weeks Viral kinetic parameters were estimated with a bi-phasic mathematical model of HBV DNA by using compartments of free virus, infected cells, and uninfected target cells. The model parameter of interest was the effectiveness of the drug in blocking virus production from infected cells (efficacy, ε). Blocking efficiency was within the range between 0 and 1.
Number of Patients Who Are Polymerase Chain Reaction (PCR) Negative At Week 12 PCR negative was considered \<300 copies/mL. PCR positive was considered =\>300 copies/mL.
Trial Locations
- Locations (8)
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Gachon Univ. Gil Medical Center Hospital
🇰🇷Incheon, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Medical Center_Anam
🇰🇷Seoul, Korea, Republic of
Holy Family Hospital_Bucheon
🇰🇷Bucheon,Kyunggi, Korea, Republic of
Kangnam Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of