Scientific Publications by FDA Staff

Clin Pharmacol Ther 2017 Dec;102(6):951-60

Model-based approach for optimizing study design and clinical drug performances of extended-release formulations of methylphenidate for the treatment of ADHD.

Gomeni R, Bressolle-Gomeni F, Spencer TJ, Faraone SV, Fang L, Babiskin A

Methylphenidate (MPH) is currently used to treat children with attention deficit hyperactivity disorder (ADHD). Several extended-release (ER) formulations characterized by a dual release process were developed to improve efficacy over an extended duration. In this study, a model-based approach using literature data was developed to: a) evaluate the most efficient pharmacokinetic (PK) model to characterize the complex PK profile of MPH ER formulations; b) provide PK endpoint metrics for comparing ER formulations; c) define criteria for optimizing development of ER formulations using a convolution-based model linking in-vitro release, in-vivo release and hour-by-hour behavioral ratings of ADHD symptoms; and d) define an optimized trial design for assessing the activity of MPH in pediatric populations. The convolution-based model accurately described the complex PK profiles of a variety of ER MPH products, providing a natural framework for establishing an in-vitro/in-vivo correlation and for defining criteria for assessing comparative bioequivalence of MPH ER products.