A phase I, randomized, double-blind, single-dose pharmacokinetic study to evaluate the biosimilarity of SB16 (proposed denosumab biosimilar) with reference denosumab in healthy male subjects

Background: SB16 is a biosimilar to reference denosumab (DEN).This study assessed pharmacokinetic (PK) equivalence and evaluated pharmacodynamic (PD), safety, tolerability, and immunogenicity between SB16, European Union-sourced DEN (EU-DEN), and United States-sourced DEN (US-DEN). Research design and methods:In this double-blind, parallel group, and single-dose study, healthy male subjects were randomized 1:1:1 to receive a single 60 mg dose of either SB16, EU-DEN, or US-DEN subcutaneously.PK, PD, safety, and immunogenicity were evaluated for 197 days.Primary PK endpoints were area under the concentration-time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum serum concentration (C max ).Equivalence was determined if 90% confidence intervals (CIs) for the ratio of geometric least squares means (LS Means) were within the equivalence margin of 0.80 to 1.25.Results: A total of 168 subjects (56 per treatment group) were randomized.All of the corresponding 90% CI of geometric LS Means ratio of primary PK parameters were within the pre-defined equivalence margin.PD, safety, and immunogenicity profiles were also comparable between the treatment groups.