Randomised clinical trial: safety, efficacy and pharmacokinetics of HS-10234 versus tenofovir for the treatment of chronic hepatitis B infection.

Abstract

HS-10234 is a novel prodrug of tenofovir developed to increase anti-viral potency and to reduce systemic toxicities. To evaluate the tolerability, pharmacokinetics and anti-viral efficacy of HS-10234 in patients with chronic hepatitis B (CHB) infection METHODS: Treatment-naïve subjects with non-cirrhotic CHB were divided into three groups (n=12/group) and randomised within each group to receive 10, 25 or 40mg of HS-10234, or 300mg of tenofovir disoproxil fumarate (TDF) once a day for 28days. Among 36 enrolled subjects, 33.3% were hepatitis B e antigen-negative with a mean hepatitis B virus (HBV) DNA level of 6.32-7.42log10 IU/mL. Nephrotoxicity and serious adverse events were not observed; all adverse events were mild or moderate and non-specific. The mean reductions in serum HBV DNA after 28days were -2.70, -2.89, -2.72 and -3.04log10 IU/mL for treatment with 10, 25 or 40mg HS-10234, and 300mg TDF, respectively. HS-10234 and its metabolite TFV showed linear, dose-proportional pharmacokinetics. The concentrations of active TFV-DP in peripheral blood mononuclear cells were higher (approximately 2- to 11-fold increase) and TFV in plasma were lower (approximately 4.5- to 25-fold reduction) in subjects taking HS-10234 than those in the TDF group. HS-10234 was well tolerated during a 4-week course. TDF and HS-10234 had comparable potency in inhibiting HBV replication. A daily dose of 10-25mg of HS-10234 is recommended for CHB treatment. (Chinese Drug Trial Identifier: CTR20161077).