Non-Inferior Efficacy of Tenofovir Disoproxil to Tenofovir Disoproxil Fumarate in Virologically Suppressed Chronic Hepatitis B Patients

Abstract

Purpose: Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formula-tion, removing fumarate to improve the ease of oral intake by reducing the tablet&apos;s size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB).Patients and Methods: CHB patients with HBV-DNA <69 IU/mL after >= 24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA <69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities.Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was -2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; -0.8 +/- 9.8 versus -2.4 +/- 12.8 mL/min, respectively (P=0.017).Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.