title: Randomized prospective study showing the non-inferiority of tenofovir to entecavir in treatment-naïve chronic hepatitis B patients.
abstract: OBJECTIVE
  The study aimed to evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) and entecavir hydrate (ETV) in nucleos(t)ide analog (NA)-naïve Japanese chronic hepatitis B (CHB) patients.
  
  
  METHODS
  This multicenter, randomized, double-blinded study assessing the efficacy and safety of TDF 300 mg and ETV 0.5 mg in NA-naïve CHB subjects was carried out from November 2011 to November 2014, and funded by GlaxoSmithKline. The subjects were assigned to the TDF arm or ETV arm in a 2:1 ratio. The primary efficacy endpoint was the non-inferiority of TDF to ETV at week 24.
  
  
  RESULTS
  A total of 166 subjects (TDF arm, 110; ETV arm, 56) were enrolled. The change (mean ± SE) in serum hepatitis B virus (HBV)-DNA levels from baseline to week 24 was -4.63 ± 0.044 and -4.50 ± 0.063 log10copies/mL in the TDF and ETV arms, respectively, indicating the non-inferiority of TDF to ETV (P < 0.0001). The proportion of subjects with undetectable HBV-DNA increased from 54 to 77% and 39 to 66% in the TDF and ETV arms with continuation of the treatment from week 24 to 48, respectively. Reduction in hepatitis B surface antigen level was greater in subjects with hepatitis B envelope antigen (+) and high alanine aminotransferase levels (≥80 IU/L). Prevalence of drug-related adverse events at week 48 was 20% and 18% in the TDF and ETV arms, respectively.
  
  
  CONCLUSIONS
  The study is the first to report that TDF has non-inferiority to ETV in treatment effectiveness (lowering of serum HBV-DNA level) at week 24. ClinicalTrials.gov trial registration nos. NCT01480284 and GSK LOC115409.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.affiliation: Medicines Development, GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Suyama
authors.affiliation: Medicines Development, GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Biomedical Data Sciences, GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Medical Affairs, GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sugiura
keywords: CHB; HBsAg; entecavir; randomized prospective study; tenofovir