title: A randomized placebo-controlled, dose-finding study of oral LB80380 in HBeAg-positive patients with chronic hepatitis B.
abstract: BACKGROUND
  LB80380 is potent antiviral agent against hepatitis B virus (HBV) in vitro and in the woodchuck model. It has an excellent preclinical safety profile including lower potential for renal toxicity than adefovir. It is effective against both wild-type and YMDD mutant HBV. LB80380 is converted to its parent drug, LB80331, after oral absorption, and further metabolized to its active form, LB80317.
  
  
  OBJECTIVE
  This randomized placebo-controlled Phase I/II clinical study of LB80380 was conducted to assess the safety, antiviral activity and pharmacokinetics of its parent drug LB80331 and its active form LB80317 in 29 Asian adults with chronic hepatitis B positive for hepatitis B e antigen in four escalating dose groups (30, 60, 120 and 240 mg once per day) for 4 weeks with a 12-week follow-up period.
  
  
  RESULTS
  The mean maximum HBV DNA reduction was 3.05, 4.20, 3.67 and 3.68 log10 copies/ml for 30, 60, 120 and 240 mg per day, respectively. Viral dynamic analysis suggested a high degree of inhibition of HBV replication at doses of 60 mg or higher per day. LB80380 was well tolerated at all dose groups, and no dose-related clinical or laboratory adverse event was reported.
  
  
  CONCLUSIONS
  LB80380 is shown to be a potent and safe antiviral agent for HBV. Marked HBV DNA suppression was observed in all dose groups. The HBV DNA suppression was approximately constant at doses of 60 mg and higher over the 28-day dosing period. The dose response of LB80380 will be evaluated further in large clinical studies.
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong. mfyuen@hkucc.hku.hk
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Chung Ryeol
authors.initials: CR
authors.lastname: Kim
authors.forename: Vincent
authors.initials: V
authors.lastname: Ngai
authors.forename: John Chi-Hang
authors.initials: JC
authors.lastname: Yuen
authors.forename: Changhee
authors.initials: C
authors.lastname: Min
authors.forename: Hyang Mi
authors.initials: HM
authors.lastname: Kang
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: C487369:((1-((2-amino-9H-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonic acid dipivoxyl; D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D006147:Guanine