A collaborative research project led by FDA (Division of Clinical Pharmacology [DCP] and Division of Pharmacometrics [DPM] in the Office of Clinical Pharmacology [OCP], and Division of Neurology Products [DNP] in the Office of New Drugs [OND]), and supported by the Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) and the Center for Translational Medicine (CTM) at the University of Maryland, Baltimore (UMB) School of Pharmacy, has resulted in a conclusion that extrapolation of the efficacy results from adults to children 4 years of age and older with POS is acceptable and that independent clinical efficacy trials in these children will not be needed.
Antiepileptic drugs (AEDs) are a diverse group of pharmaceuticals used in the treatment of various types of epileptic seizures. Generally, AEDs are initially developed as adjunctive therapy to treat POS, the most commonly occurring type of seizures, in adults. Expansion of the indication to pediatrics frequently follows the adult approval and typically has been supported by at least one adequate and well-controlled clinical trial in the pediatric population. As a result, a number of AEDs now have a pediatric indication based on clinical trial data. The overall goal of this project was to consider whether the accumulated evidence from clinical trials with multiple AEDs would be sufficient to support extrapolation of efficacy from adult to pediatric patients for the treatment of partial seizures, and under what circumstances such extrapolation would be appropriate.
This Center for Drug Evaluation and Research (CDER) Critical Path program funded project was led by OCP and supported by DNP. The fellows hired from UMB, in collaboration with OCP staff, created a clinical trial database and performed exposure-response analyses to bridge POS adjunctive treatment data between adult and pediatric patients. PEACE provided supportive clinical expertise in describing disease and intervention similarities between adult and pediatric patients.
The project required the screening of all approved AEDs for identification of drugs having efficacy clinical trials in both adult and pediatric patients for adjunctive therapy of POS. For the identified AEDs, quantitative PK and PK/PD analyses were conducted for PK/PD and clinical endpoints datasets collected from both FDA databases and the pharmaceutical companies. The investigators concluded that the pathophysiology of POS in adult and pediatric patients 4 years of age and older is similar. This conclusion allowed for the subsequent evaluation of the exposure-response relationships and of relevant covariates (e.g., class of AED, age). Based on these analyses, FDA concluded that extrapolation of efficacy from adult to pediatric patients 4 years of age and older with POS is acceptable.
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This burst was prepared by the Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.