Study 1 and Study 2 showed comparable serum drug concentration-time profiles and PK parameters for both FKB327 and the RP, supporting PK similarity between both drugs, as previously reported [12]. measurable concentration (AUC0-t) and maximum serum concentration; area under the concentration-time curve from time zero to 360?h was also evaluated as one of the main endpoints in Study 1. Biosimilarity in terms of pharmacokinetics was decided if the 90% confidence interval of the mean difference in geometric mean ratio of all main PK parameters was within the prespecified equivalence criteria (0.80C1.25). Immunogenicity and security were also evaluated as secondary endpoints. Results The serum concentration-time profiles were comparable between the FKB327 and the RP treatment groups in both studies. Primary PK parameters were within the prespecified bioequivalence range in Study 2, although AUC0-t Dorsomorphin 2HCl was slightly outside the upper side of the range in Study 1. No differences in safety profile were observed in these studies. The incidence of anti-drug antibodies (ADAs) and impact of ADAs on PK profile were similar among the treatment groups in both studies. Conclusion Biosimilarity between FKB327 and the RP after a single 40-mg SC injection was confirmed in healthy Japanese male participants by modifying the study design. Trial registration jRCT2071200058 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200058, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200058) and jRCT2071200057 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200057, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200057). Retrospectively registered 25/11/2020. Supplementary Information The online version contains supplementary material available at 10.1186/s40360-021-00545-3. Keywords: Adalimumab, Bioequivalence, Biosimilar, FKB327, Japanese, Pharmacokinetics Background Adalimumab, a recombinant human immunoglobulin G1 monoclonal antibody, binds specifically to human tumor necrosis factor (TNF)- and neutralizes the biological function of TNF [1C3]. Adalimumab has been approved as a treatment for rheumatoid arthritis, psoriasis, inflammatory bowel disease, and other chronic immune-mediated inflammatory diseases in the United States, the European Union, Japan, and other countries worldwide under the trade name Humira?, hereafter referred to as the reference product (RP) [1C3]. The RP is usually administered subcutaneously every 2?weeks, with a fixed dosage in adults [2]. However, high pharmacokinetic (PK) variability of the drug has been reported after subcutaneous (SC) injection [3, 4]. Anti-drug antibodies (ADAs) were detected by high-sensitivity ADA assay methods used in recent biosimilar studies [5, 6], although a low ADA-positive ratio was reported in initial studies using a standard ADA assay method [7]. Given the wider PK variability of the RP, healthy male participants comprising a more homogeneous populace without immunosuppressive conditions are considered a more sensitive populace in which to assess the PK similarity of its biosimilar product [8C10]. FKB327 is usually a monoclonal antibody produced in the Chinese hamster ovary cells transfected with complementary DNA encoding the heavy and light chain of the RP and has been developed as a biosimilar of the RP [2]. It has been reported that, along with physicochemical and biological similarities, the PK of FKB327 is similar to that of the US-approved and EU-licensed RP [11, 12]. In addition, FKB327 showed comparable efficacy and security compared to the RP in patients with rheumatoid arthritis [13, 14]. To evaluate the PK similarity of FKB327 compared with the RP in a Japanese populace, 2 biosimilarity studies were performed in accordance with Japanese biosimilar guidance, which requires Japanese study participants to be included in either a comparative PK or comparative clinical efficacy study [15]. That is, because the initial Dorsomorphin 2HCl FKB327C004 study (Study 1) did not fully confirm the biosimilarity with reference to the general bioequivalence criteria of all main PK endpoints, the Dorsomorphin 2HCl FKB327C006 study (Study 2) was designed to confirm biosimilarity between the study drugs by modifying Rabbit Polyclonal to YOD1 the study design. Here, we statement the outcomes of the 2 2 biosimilarity studies comparing FKB327 with the RP in healthy.