title: A Randomized Phase I Pharmacokinetic Study Comparing Biosimilar Candidate SB3 and Trastuzumab in Healthy Male Subjects.
abstract: This first-in-human study with SB3 was designed to evaluate the pharmacokinetic (PK) equivalence between SB3 and trastuzumab sourced in the European Union (EU trastuzumab), between SB3 and trastuzumab sourced in the United States (US trastuzumab), and between EU and US trastuzumab (NCT02075073).
  
  
  
  In this randomized, double-blind, parallel group, single-dose comparative PK study, 109 healthy male subjects were randomized to receive a single 6-mg/kg IV dose of SB3, EU -trastuzumab, or US trastuzumab. The PK parameters were calculated using noncompartmental methods. The PK equivalence in terms of AUC0--∞), AUC0-last, and Cmax for the pairwise comparisons (SB3 vs EU trastuzumab, SB3 vs US trastuzumab, and EU trastuzumab vs US trastuzumab) were determined using the predefined equivalence margin of 0.8 to 1.25.
  
  
  
  Baseline demographic characteristics for the randomized subjects were similar across the 3 groups. The 90% CIs for the geometric least square means of the AUC0-∞, AUC0-last, and Cmax were completely contained within the margin of 0.8 to 1.25. The proportions of subjects who experienced adverse events related to the study drug were 36.1%, 44.4%, and 61.1% in the SB3, EU trastuzumab, and US trastuzumab groups, respectively. The most frequently reported adverse events related to the study drug was infusion-related reactions. No subjects had positive results for antidrug antibodies after a single dose of SB3, EU trastuzumab, or US trastuzumab.
  
  
  
  This study revealed PK equivalence between SB3 and EU trastuzumab, between SB3 and US trastuzumab, and between EU trastuzumab and US trastuzumab. SB3 is well tolerated without tolerability concerns after single-dose administration in healthy male subjects.
authors.affiliation: University Hospital Jean Minjoz, INSERM 1098, Besancon, France. Electronic address: Xavier.Pivot@univ-fcomte.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
authors.affiliation: University Hospital Jean Minjoz, INSERM 1098, Besancon, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Curtit
authors.affiliation: Samsung Bioepis Co Ltd, Incheon, Republic of Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: PAREXEL International Early Phase Clinical Unit, Berlin, Germany.
authors.forename: George
authors.initials: G
authors.lastname: Golor
authors.affiliation: PAREXEL International Early Phase Clinical Unit, Berlin, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Gauliard
authors.affiliation: Samsung Bioepis Co Ltd, Incheon, Republic of Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Shin
authors.affiliation: Samsung Bioepis Co Ltd, Incheon, Republic of Korea.
authors.forename: Youngdoe
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Samsung Bioepis Co Ltd, Incheon, Republic of Korea.
authors.forename: Hansook
authors.initials: H
authors.lastname: Kim
authors.affiliation: PAREXEL International Early Phase Clinical Unit, Berlin, Germany.
authors.forename: Rainard
authors.initials: R
authors.lastname: Fuhr
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D059451:Biosimilar Pharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D019921:Biotinylation; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068878:Trastuzumab / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D059451:Biosimilar Pharmaceuticals; D000068878:Trastuzumab
keywords: Herceptin(®); biosimilars; breast cancer; pharmacokinetic equivalence; trastuzumab