title: Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus.
abstract: OBJECTIVE
  Belimumab, an anti-B lymphocyte stimulator (BLyS) human monoclonal antibody, was approved in the United States, Canada and European Union for the treatment of the patients with systemic lupus erythematosus (SLE). However, belimumab had not been evaluated in Japanese patients. The objectives of this study were to evaluate the safety and tolerability of belimumab in Japanese patients with SLE, as well as to investigate the pharmacokinetics (PK) and biological activity of belimumab in this population.
  
  
  METHODS
  A total of 12 Japanese patients were enrolled in a randomized, single-blind, placebo-controlled, dose-ascending design study. A dosing regimen of a single intravenous infusion over 1 hour of belimumab (1 mg/kg and 10 mg/kg) was employed. Patients were followed for 84 days after dosing to assess adverse events, pharmacokinetics, biomarkers and SLE disease activity.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier is NCT01381536.
  
  
  RESULTS
  Belimumab (1 mg/kg and 10 mg/kg) demonstrated a favorable clinical safety and tolerability profile in Japanese patients with SLE. The incidence of adverse events was similar among the two belimumab groups and placebo group. The PK profile of single-dose belimumab was approximately dose proportional, and the long terminal elimination half-life (12.4-15.7 days), low clearance (3.55-4.65 mL/day/kg), and small volume of distribution (76.2-80.1 mL/kg) were consistent with a fully humanized antibody. Effects of belimumab on B cells suggested biological activity effects expected as an inhibitor of BLyS.
  
  
  CONCLUSIONS
  The small sample size and single dose design of this study prevent definitive conclusions regarding the safety, pharmacokinetics or pharmacodynamics of belimumab in a Japanese population being made.
  
  
  CONCLUSIONS
  The preliminary safety, PK profile, and observed biological activity of belimumab support further evaluation of its safety and efficacy in Japanese patient with SLE.
authors.affiliation: Medicines Development, Japan Development & Medical Affairs Division, GlaxoSmithKline K.K., TokyoJapan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Medicines Development, Japan Development & Medical Affairs Division, GlaxoSmithKline K.K., TokyoJapan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Akita
authors.affiliation: Medicines Development, Japan Development & Medical Affairs Division, GlaxoSmithKline K.K., TokyoJapan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Clinical Pharmacology Department, Medicines Development, Japan Development & Medical Affairs Division, GlaxoSmithKline K.K., TokyoJapan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Biomedical Data Sciences Department, Japan Development & Medical Affairs Division, GlaxoSmithKline K.K., TokyoJapan.
authors.forename: Akira
authors.initials: A
authors.lastname: Endo
authors.affiliation: Clinical Safety & PMS, Japan Development & Medical Affairs Division, GlaxoSmithKline K.K., TokyoJapan.
authors.forename: Pascal
authors.initials: P
authors.lastname: Yoshida
keywords: Belimumab; Pharmacodynamics; Pharmacokinetics; Safety; Systemic lupus erythematosus