title: Pharmacokinetics of tralokinumab in adolescents with asthma: implications for future dosing.
abstract: OBJECTIVE
  Tralokinumab, an investigational human immunoglobulin G4 monoclonal antibody, potently and specifically neutralizes interleukin-13, a central mediator of asthma. Tralokinumab has shown improvements in clinical endpoints in adults with uncontrolled asthma. The present study explored the pharmacokinetics (PK) and safety of a single tralokinumab dose, and utilized a population PK modelling and simulation approach to evaluate the optimal dosing strategy for adolescents.
  
  
  METHODS
  Adolescent subjects with asthma, using daily controller medication, received a single subcutaneous dose of tralokinumab 300 mg. Safety, immunogenicity and PK data were collected during a 57-day follow-up. A population PK model was developed using data from the present study and prior studies in adults. Simulations were performed to evaluate dose adjustment requirements for adolescents.
  
  
  RESULTS
  Twenty adolescents (12-17 years) were enrolled; all completed the study. No clinically relevant safety findings or antidrug antibodies were detected. PK parameters were similar to those observed in adults. PK modelling showed that body weight was a minor predictor of tralokinumab PK; after incorporating body weight into the PK model, a 15% (nonparametric 95% confidence interval 5%, 26%) lower clearance was found in adolescents compared with adults [173 (151, 209) vs. 204 (191, 229) ml day(-1)]. Simulations showed no therapeutically relevant differences in exposures between adolescent and adult populations, and similar PK profiles for weight-based (4 mg kg(-1)) and fixed (300 mg) fortnightly subcutaneous doses of tralokinumab.
  
  
  CONCLUSIONS
  Single-dose administration of tralokinumab 300 mg in adolescents was well tolerated, with a PK profile similar to that in adults. Exposure predictions suggest that dose adjustment is not required for adolescents.
authors.affiliation: Clinical Pharmacology, Drug Metabolism and Pharmacokinetics, MedImmune, Cambridge, UK.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Baverel
authors.affiliation: Clinical Development, MedImmune, Cambridge, UK.
authors.forename: Meena
authors.initials: M
authors.lastname: Jain
authors.affiliation: Department of Paediatrics and Allergy, Medical University of Łódź, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Stelmach
authors.affiliation: Biostatistics, MedImmune, Gaithersburg, MD, USA.
authors.forename: Dewei
authors.initials: D
authors.lastname: She
authors.affiliation: Clinical Pharmacology, Drug Metabolism and Pharmacokinetics, MedImmune, Cambridge, UK.
authors.forename: Balaji
authors.initials: B
authors.lastname: Agoram
authors.affiliation: Clinical Operations, MedImmune, Cambridge, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Sandbach
authors.affiliation: Clinical Development, MedImmune, Cambridge, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Piper
authors.affiliation: Department of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Łódź, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuna
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008954:Models, Biological
chemical_list: D000911:Antibodies, Monoclonal; C574065:tralokinumab
keywords: Adolescent; Asthma; Tralokinumab; dosing; interleukin-13; population pharmacokinetic modelling