Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine

Purpose: We conducted exposure-response modeling and simulations to compare the predicted efficacy of extended-release oxcarbazepine (OXC-XR), an oral once-daily (qd) antiepileptic drug, with that of immediate-release (IR) OXC twice-daily (bid) when the agents are used as monotherapy or adjunctive t...

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Bibliographic Details
Published in:Clinical pharmacology: advances and applications 2020-09, Vol.12, p.135
Main Authors: Nasser, Azmi, Schwabe, Stefan, Gomeni, Roberto, Faison, Shamia, Mendes, Shannon, O'Neal, Welton
Format: Article
Language:English
Subjects:
Analysis
Brivaracetam
Drug approval
Epilepsy
Oxcarbazepine
Perampanel
Pharmaceutical industry
Seizures (Medicine)
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Summary:Purpose: We conducted exposure-response modeling and simulations to compare the predicted efficacy of extended-release oxcarbazepine (OXC-XR), an oral once-daily (qd) antiepileptic drug, with that of immediate-release (IR) OXC twice-daily (bid) when the agents are used as monotherapy or adjunctive therapy in patients with epilepsy characterized by partial-onset seizures (POS). Methods: Modeling assessed percent change from baseline 28-day seizure frequency (PCH) as a function of minimum concentration ([C.sub.min]) of monohydroxy derivative (MHD), the clinically relevant metabolite of OXC. For OXC-IR, the model used historical data; values for OXC-XR were derived from observed data. The model was simulated (N=100) to predict PCH at MHD [C.sub.min] concentrations achieved with 1200 and 2400 mg/day in adults and children receiving OXC-XR qd or OXC-IR bid. Mean PCH and 95% confidence intervals (CIs) were generated and compared. Results: Predicted efficacy was not different (ie, 95% CI of mean PCH overlapped) for OXC-XR qd vs OXC-IR bid at mean MHD [C.sub.min] concentrations achieved with 1200 and 2400 mg/day adjunctive OXC-XR (47.4 and 76.4 [micro]mol/L) and at target MHD [C.sub.mim] concentrations for OXC-IR monotherapy (59.1 and 112 [micro]mol/L) in adults. Predicted efficacy in adults vs children was not different between formulations. Depending on MHD [C.sub.min], the predicted mean PCH in adults ranged from -51.4% to -73.4% with OXC-XR qd and -53.2% to -78.5% with OXC-IR bid. In children, the predicted mean PCH ranged from -48.4% to -58.1% (OXC-XR qd) and -32.5% to -70.4% (OXC-IR bid). Conclusion: This model-based analysis predicted comparable efficacy for OXC-XR qd vs OXC-IR bid at MHD [C.sub.min] concentrations corresponding to 1200 and 2400 mg/day as monotherapy or adjunctive therapy. Based on this analysis, the US Food & Drug Administration approved OXC-XR for use as monotherapy in adults and children [greater than or equal to]6 years of age with POS. Keywords: oxcarbazepine, monotherapy, Oxtellar, monohydroxy derivative, adjunctive therapy
ISSN:1179-1438
1179-1438