Pharmacokinetics of tralokinumab in adolescents with asthma: implications for future dosing

• Published in: British journal of clinical pharmacology 2015-12, Vol.80 (6), p.1337-1349
• Main Authors: Baverel, Paul G., Jain, Meena, Stelmach, Iwona, She, Dewei, Agoram, Balaji, Sandbach, Sara, Piper, Edward, Kuna, Piotr
• Format: Article
• Language: English
• Subjects: Adolescent; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Asthma; Asthma - drug therapy; Asthma - physiopathology; Child; Clinical Trials; dosing; Female; Forced Expiratory Volume; Humans; interleukin‐13; Male; Models, Biological; population pharmacokinetic modelling; Tralokinumab
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12725

Aims 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. Conclusion 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.