Back to Journals » Clinical Pharmacology: Advances and Applications » Volume 12

Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation

Authors Faison S, Gomeni R, Mendes S, O'Neal W, Schwabe S, Nasser A

Received 5 April 2020

Accepted for publication 15 August 2020

Published 23 September 2020 Volume 2020:12 Pages 135—147


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Professor Arthur Frankel

Shamia Faison,1 Roberto Gomeni,2 Shannon Mendes,1 Welton O’Neal,1 Stefan Schwabe,1 Azmi Nasser1

1Supernus Pharmaceuticals, Inc., Rockville, MD, USA; 2PharmacoMetrica, La Fouillade, France

Correspondence: Azmi Nasser
Supernus Pharmaceuticals, Inc., 9715 Key West Avenue, Rockville, MD 20850, USA
Tel +1 301 838 2500
Fax +1 240 403 0065

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 (Cmin) 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 Cmin 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 Cmin concentrations achieved with 1200 and 2400 mg/day adjunctive OXC-XR (47.4 and 76.4 μmol/L) and at target MHD Cmin concentrations for OXC-IR monotherapy (59.1 and 112 μmol/L) in adults. Predicted efficacy in adults vs children was not different between formulations. Depending on MHD Cmin, 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 Cmin 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 ≥ 6 years of age with POS.

Keywords: oxcarbazepine, monotherapy, Oxtellar, monohydroxy derivative, adjunctive therapy

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]