title: A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B.
abstract: OBJECTIVE
  A previous 4-week trial of telbivudine in patients with chronic hepatitis B indicated marked antiviral effects with good tolerability, leading to the present 1-year phase 2b trial.
  
  
  METHODS
  This randomized, double-blind, multicenter trial evaluated the efficacy and safety of telbivudine 400 or 600 mg/day and telbivudine 400 or 600 mg/day plus lamivudine 100 mg/day (Comb400 and Comb600) compared with lamivudine 100 mg/day in hepatitis B e antigen (HBeAg)-positive adults with compensated chronic hepatitis B.
  
  
  RESULTS
  A total of 104 patients were randomized 1:1:1:1:1 among the 5 groups. Median reductions in serum hepatitis B virus (HBV) DNA levels at week 52 (log(10) copies/mL) were as follows: lamivudine, 4.66; telbivudine 400 mg, 6.43; telbivudine 600 mg, 6.09; Comb400, 6.40; and Comb600, 6.05. At week 52, telbivudine monotherapy showed a significantly greater mean reduction in HBV DNA levels (6.01 vs 4.57 log(10) copies/mL; P < .05), clearance of polymerase chain reaction-detectable HBV DNA (61% vs 32%; P < .05), and normalization of alanine aminotransferase levels (86% vs 63%; P < .05) compared with lamivudine monotherapy, with proportionally greater HBeAg seroconversion (31% vs 22%) and less viral breakthrough (4.5% vs 15.8%) (P = NS for both). Combination treatment was not better than telbivudine alone. All treatments were well tolerated. In exploratory scientific analyses, clinical efficacy at 1 year appeared related to reduction in HBV DNA levels in the first 6 months of treatment.
  
  
  CONCLUSIONS
  Patients with chronic hepatitis B treated with telbivudine exhibited significantly greater virologic and biochemical responses compared with lamivudine. Results with the combination regimens were similar to those obtained with telbivudine alone. These data support the ongoing phase 3 evaluation of telbivudine for treatment of patients with chronic hepatitis B.
authors.affiliation: University of Hong Kong, China. hrmelcl@hkucc.hku.hk
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Nancy
authors.initials: N
authors.lastname: Leung
authors.forename: Eng-Kiong
authors.initials: EK
authors.lastname: Teo
authors.forename: Myron
authors.initials: M
authors.lastname: Tong
authors.forename: Florence
authors.initials: F
authors.lastname: Wong
authors.forename: Hie-Won
authors.initials: HW
authors.lastname: Hann
authors.forename: Steven
authors.initials: S
authors.lastname: Han
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Maureen
authors.initials: M
authors.lastname: Myers
authors.forename: George
authors.initials: G
authors.lastname: Chao
authors.forename: Deborah
authors.initials: D
authors.lastname: Lloyd
authors.forename: Nathaniel A
authors.initials: NA
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008111:Liver Function Tests; D008134:Long-Term Care; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009705:Nucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D019259:Lamivudine; D013936:Thymidine