Journal
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 80, Issue 6, Pages 1337-1349Publisher
WILEY
DOI: 10.1111/bcp.12725
Keywords
Adolescent; Asthma; dosing; interleukin-13; population pharmacokinetic modelling; Tralokinumab
Categories
Funding
- MedImmune
- AstraZeneca
- GlaxoSmithKline
- Novartis
- Boehringer Ingelheim
- Teva
- Chiesi
- Almirall
- Polpharma
- Adamed
- Celon Pharma
- Polfarmex
- Sandoz
- MSD
- Faes Farma
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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.
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