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

Abstract

SummaryBackgroundHS‐10234 is a novel prodrug of tenofovir developed to increase anti‐viral potency and to reduce systemic toxicities.AimsTo evaluate the tolerability, pharmacokinetics and anti‐viral efficacy of HS‐10234 in patients with chronic hepatitis B (CHB) infectionMethodsTreatment‐naïve subjects with non‐cirrhotic CHB were divided into three groups (n = 12/group) and randomised within each group to receive 10, 25 or 40 mg of HS‐10234, or 300 mg of tenofovir disoproxil fumarate (TDF) once a day for 28 days.ResultsAmong 36 enrolled subjects, 33.3% were hepatitis B e antigen‐negative with a mean hepatitis B virus (HBV) DNA level of 6.32‐7.42 log10 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 28 days were −2.70, −2.89, −2.72 and −3.04 log10 IU/mL for treatment with 10, 25 or 40 mg HS‐10234, and 300 mg 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.ConclusionsHS‐10234 was well tolerated during a 4‐week course. TDF and HS‐10234 had comparable potency in inhibiting HBV replication. A daily dose of 10‐25 mg of HS‐10234 is recommended for CHB treatment. (Chinese Drug Trial Identifier: CTR20161077).