Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B

• Change in Mean HBV DNA Level [ Time Frame: Baseline (day 1) to Weeks 2, 4, 8 ] [ Designated as safety issue: No ]
  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. [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
  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.
• Change in Alanine Aminotransferase (ALT) Levels [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
• Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]

  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 Rate of Infected Cell Loss [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]

  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 [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
  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 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
  PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL.

• • Change in mean HBV DNA level from Baseline to Weeks 2, 4, and 8
• Characterization of very early viral kinetics through estimation of various parameters
• Change in ALT (alanine aminotransferase) levels from Baseline to Week 12
• The area under the curve (AUC) of HBV DNA change from Baseline to Week 12
• % patients who are polymerase chain reaction (PCR) negative at Week 12
• Safety assessed by adverse events and laboratory values

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.

• Hepatitis B
• Chronic Hepatitis B

• Drug: Entecavir
  Entecavir 0.5 mg once daily for 12 weeks.
• Drug: Telbivudine
  Telbivudine 600 mg once daily for 12 weeks.

• Experimental: Telbivudine
  Intervention: Drug: Telbivudine
• Active Comparator: Entecavir
  Intervention: Drug: Entecavir

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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