Using Modified QbD to Develop a Novel Pediatric Formulation of Ezogabine
March 03, 2021
An adult tablet formulation of ezogabine (retigabine) (i.e., Potiga [also known as Trobalt]) was developed and marketed by GlaxoSmithKline (GSK), as an adjunctive treatment for focal-onset epilepsy in adults. Ezogabine is a potassium channel opener and primarily works by activating the voltage-gated potassium channels in the brain. Ezogabine was shown to be an effective treatment for many patients, however; under certain conditions, it could generate cyclized dimers, some of which have been implicated in pigmentation abnormalities in a subset of patients. Even though these abnormalities were reversible and had no toxic effects, they may have played a part in the decision to withdraw the drug from the global market in 2017.
Potiga had never been studied in a formal clinical trial in young children, but crushed and/or compounded Potiga tablets have been used, off-label, to treat children affected by developmental and epileptic encephalopathy, often with favorable outcomes. The efficacy of this off-label treatment has highlighted a need for clinical testing of ezogabine in the pediatric population. The first step is developing a suitable pediatric formulation of ezogabine (XEN496). A formulation has been developed that is compatible with a range of food matrices, chemically stable, bioequivalent to Potiga in a rat model, compatible with feeding bottle plastics, and has a pleasant taste and mouth feel.
