title: Pharmacokinetic bridging approach for developing biologics-delivery devices: a case study with a golimumab autoinjector.
abstract: OBJECTIVE
  This Phase 1 pharmacokinetic (PK) comparability study in healthy subjects was performed to compare the PK properties and tolerability of single-dose golimumab 100 mg delivered subcutaneously by an autoinjector device or by a standard needle and syringe that had been used for the subcutaneous (SC) delivery of golimumab in pivotal Phase 3 studies.
  
  
  METHODS
  Healthy male subjects were randomly assigned to receive a single injection of SC golimumab 100 mg using either the autoinjector or a standard needle and syringe. The PK parameters of golimumab were calculated using noncompartmental analysis. An ANOVA model was applied to compare the 2 injection methods with regard to golimumab C(max) and the AUC from 0 and 49 days after administration (AUC(0-49d)).
  
  
  RESULTS
  In the prespecified evaluable PK population (n = 141), the mean (SD) values for C(max) were 6.6 (3.3) and 6.0 (3.0) µg/mL, and AUC(0-49d) values were 97.4 (43.2) and 88.9 (36.8) µg·d/mL in the autoinjector and needle/syringe groups, respectively. The 90% CI of the geometric mean ratios of the AUC(0-49d) values between the 2 delivery methods was 95.17% to 120.55%; the 90% CI of the geometric mean ratio of C(max) was 96.14% to 127.42%. In a post hoc intent-to-treat analysis using data from all 156 subjects, the 90% CIs of both C(max) and AUC(0-49d) fell within the prespecified range for bioequivalence (80% to 125%). The prevalences of adverse events were similar between the 2 groups.
  
  
  CONCLUSIONS
  The totality of the study findings suggests that the PK properties and tolerability of SC administration of golimumab by the 2 delivery methods were comparable. The study results successfully bridged the container-closure change from a liquid-in-vial product to either a prefilled syringe or an autoinjector with the same liquid formulation.
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Marciniak
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Bart
authors.initials: B
authors.lastname: Frederick
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Lilianne
authors.initials: L
authors.lastname: Kim
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Davis
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania. Electronic address: hzhou2@its.jnj.com.
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D004868:Equipment Failure; D064368:Healthy Volunteers; D006801:Humans; D007279:Injections, Subcutaneous / Q000295:instrumentation; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D002214:Capsules; C529000:golimumab
keywords: absorption; bioequivalence; comparability; golimumab; monoclonal antibody; pharmacokinetics