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

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

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, FranceCorrespondence: Azmi NasserSupernus Pharmaceuticals, Inc., 9715 Key West Avenue, Rockville, MD 20850, U...

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Autores principales: Faison S, Gomeni R, Mendes S, O'Neal W, Schwabe S, Nasser A
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2020
Materias:
oxcarbazepine
monotherapy
oxtellar
monohydroxy derivative
adjunctive therapy
Therapeutics. Pharmacology
RM1-950
Acceso en línea:https://doaj.org/article/775ab1524b2142b4a1084b0ad7db2d39
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spelling oai:doaj.org-article:775ab1524b2142b4a1084b0ad7db2d392021-12-02T11:16:18ZPredicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation1179-1438https://doaj.org/article/775ab1524b2142b4a1084b0ad7db2d392020-09-01T00:00:00Zhttps://www.dovepress.com/predicted-efficacy-of-once-daily-extended-release-oxcarbazepine-oxtell-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Shamia 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, FranceCorrespondence: Azmi NasserSupernus Pharmaceuticals, Inc., 9715 Key West Avenue, Rockville, MD 20850, USATel +1 301 838 2500Fax +1 240 403 0065Email anasser@supernus.comPurpose: 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 therapyFaison SGomeni RMendes SO'Neal WSchwabe SNasser ADove Medical Pressarticleoxcarbazepinemonotherapyoxtellarmonohydroxy derivativeadjunctive therapyTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 12, Pp 135-147 (2020)
institution DOAJ
collection DOAJ
language EN
topic oxcarbazepine
monotherapy
oxtellar
monohydroxy derivative
adjunctive therapy
Therapeutics. Pharmacology
RM1-950
spellingShingle oxcarbazepine
monotherapy
oxtellar
monohydroxy derivative
adjunctive therapy
Therapeutics. Pharmacology
RM1-950
Faison S
Gomeni R
Mendes S
O'Neal W
Schwabe S
Nasser A
Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation
description 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, FranceCorrespondence: Azmi NasserSupernus Pharmaceuticals, Inc., 9715 Key West Avenue, Rockville, MD 20850, USATel +1 301 838 2500Fax +1 240 403 0065Email anasser@supernus.comPurpose: 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
format article
author Faison S
Gomeni R
Mendes S
O'Neal W
Schwabe S
Nasser A
author_facet Faison S
Gomeni R
Mendes S
O'Neal W
Schwabe S
Nasser A
author_sort Faison S
title Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation
title_short Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation
title_full Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation
title_fullStr Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation
title_full_unstemmed Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and Simulation
title_sort predicted efficacy of once-daily extended-release oxcarbazepine (oxtellar xr®) monotherapy in adults and children with partial-onset seizures: exposure-response modeling and simulation
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/775ab1524b2142b4a1084b0ad7db2d39
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