Model Informed Pediatric Development Applied to Bilastine: Ontogenic PK Model Development, Dose Selection for First...

Area of Science:

• Pharmacology
• Pediatric Medicine
• Mathematical Modeling

Background:

• Bilastine, an H1 antagonist, has established pharmacokinetics (PK) and pharmacodynamics (PD) in adults at 20 mg/day.
• Favorable characteristics suggest bilastine's utility in pediatrics, but pediatric PK/PD and optimal dosing require investigation.

Purpose of the Study:

• Develop an ontogenic predictive model for bilastine PK/PD in children based on adult data.
• Utilize the model to design a pediatric PK study.
• Confirm model predictability and dose selection with initial pediatric data, including younger children (<6 years).

Main Methods:

• A semi-mechanistic modeling approach predicted pediatric bilastine PK, assuming adult PD.
• Simulations assessed plasma levels and skin responses (wheal/flare) across various doses.
• An adaptive PK trial design was created and validated using early participant data.

Main Results:

• PK/PD simulations indicated 10 mg/day as the optimal dose for children aged 2 to <12 years.
• An interim analysis confirmed model predictions and supported the trial's continuation.

Conclusions:

• The predictive model accurately estimated bilastine PK in pediatric populations.
• The model facilitated optimal dose and sampling scheme selection for the pediatric trial.
• The chosen dose is suitable for younger children, supporting a future safety study in children aged 2 to <12 years.