All had received continuous lamivudine treatment for 6 months or more. Other inclusion criteria were: HBV DNA levels ≥1 × 106 copies/mL (measured by the COBAS Amplicor HBV Monitor assay; Roche Diagnostics, Branchburg,
NJ; lower limit of detection 300 copies/mL); ALT value between 1.5 and 10 × ULN; and for women of child-bearing potential, negative serum pregnancy test prior to study entry, and willingness to use at least two contraception methods including a barrier method. Patients with the following criteria were excluded: coinfection with hepatitis C, hepatitis D, and human immunodeficiency virus; pregnancy or breast-feeding; use of known nephrotoxic or hepatotoxic agents; treatment with Selleck NVP-AUY922 immunomodulatory agents or corticosteroids within 6 months prior to study entry; decompensated liver disease PD-0332991 cell line with clinical complications of cirrhosis; prothrombin time >3 seconds prolonged relative to the normal control; serum albumin <30 g/L and bilirubin >2.5 × ULN; or other laboratory parameters, including hemoglobin <9.0 g/dL (unless due to
haemoglobinopathy), absolute neutrophil count <1.5 × 109/L, platelet count <100 × 109/L, creatinine >133 μmol/L, serum amylase >1.5 × ULN, lipase >1.5 × ULN, alpha-fetoprotein level >20 ng/mL, and ultrasonography performed prior to baseline with findings indicative of hepatocellular carcinoma. The efficacy variable was serum HBV DNA levels. The primary efficacy endpoint was a reduction in log10 serum HBV DNA level from baseline at week 12. Secondary efficacy endpoints included: reduction in log10 serum HBV DNA level from baseline at week 4; proportion of patients with HBeAg seroconversion at week 12; proportion of patients with HBsAg seroconversion at week 12; and proportion of patients with ALT normalization at week 12. Evaluation of safety of the study drug was based on
adverse event (AE) and serious AE data, DLT data, clinical laboratory reports, physical examinations, and vital signs. The predetermined amount of creatinine increase was set as >125% of the baseline creatinine level, and this was for easy alertness of medchemexpress possible abnormal data to the investigators. HBeAg seroconversion was defined as loss of HBeAg with the development of antibody to HBeAg. Virologic rebound was defined as an increase of HBV DNA level by more than 1 log compared with the nadir in patients who achieved more than 1 log reduction of HBV DNA during the treatment period compared with baseline HBV DNA levels. Surveillance of possible LB80380 and adefovir viral mutations were not conducted because of the limited duration of LB80380 treatment of 12 weeks and adefovir treatment for 24 weeks. Evaluation of patient disposition was based on the enrolled population. The per-protocol (PP) population included all patients who were treated for at least 12 weeks with LB80380 with at least 80% compliance and had no major protocol violations.