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.

ABSTRACT

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 111 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 (Cmax). 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. CONCLUSION: This study demonstrated PK bioequivalence between SB16, EU-DEN, and US-DEN in healthy male subjects. TRIALREGISTRATION CT.gov identifier NCT04621318.