To evaluate the efficacy of Oxtellar XR® as QD monotherapy in adults and children with partial-onset seizures (POS) using exposure-response model-based approach and adjunctive efficacy data.

Oxtellar XR was approved as adjunctive therapy in adults with POS. The FDA subsequently suggested that efficacy and safety data of Oxtellar XR may be extrapolated to  monotherapy in adults and children, provided that exposure-response relationships at recommended dosages are similar for monotherapy and adjunctive therapy.

Oxtellar XR pharmacokinetic studies in adults and children with POS, and a placebo controlled trial as adjunctive therapy in adults with POS were used for the analyses (N=283). BID immediate-release OXC (Trileptal®) served as historical control (N=480). A similar model to that initially developed for Trileptal was fitted to the Oxtellar XR data and the model’s parameters were estimated. The model was simulated at the plasma therapeutic concentration ranges (C_min) of the active monohydroxylated derivative (MHD) moiety to predict the clinical response, % seizure frequency reduction normalized for 28 days (%SFR), for Oxtellar XR and OXC. The C_min ranges are corresponding to MHD concentrations achieved with 1200 and 2400 mg/day in adults and children. The %SFR mean and 95% CI were generated and compared.

The model-based analysis demonstrated that the predicted efficacy of QD Oxtellar XR as adjunctive therapy in adults support the use of QD Oxtellar XR as monotherapy in adults and children ≥6 years of age with POS.
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