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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| Format: | Article |
| Language: | English |
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Dove Medical Press
2020-09-01
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| Series: | Clinical Pharmacology: Advances and Applications |
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| Online Access: | https://www.dovepress.com/predicted-efficacy-of-once-daily-extended-release-oxcarbazepine-oxtell-peer-reviewed-article-CPAA |
| _version_ | 1818421692033138688 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-14T13:14:24Z |
| format | Article |
| id | doaj.art-775ab1524b2142b4a1084b0ad7db2d39 |
| institution | Directory Open Access Journal |
| issn | 1179-1438 |
| language | English |
| last_indexed | 2024-12-14T13:14:24Z |
| publishDate | 2020-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Pharmacology: Advances and Applications |
| spelling | doaj.art-775ab1524b2142b4a1084b0ad7db2d392022-12-21T23:00:07ZengDove Medical PressClinical Pharmacology: Advances and Applications1179-14382020-09-01Volume 1213514757287Predicted Efficacy of Once-Daily Extended-Release Oxcarbazepine (Oxtellar XR®) Monotherapy in Adults and Children with Partial-Onset Seizures: Exposure-Response Modeling and SimulationFaison SGomeni RMendes SO'Neal WSchwabe SNasser AShamia 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 therapyhttps://www.dovepress.com/predicted-efficacy-of-once-daily-extended-release-oxcarbazepine-oxtell-peer-reviewed-article-CPAAoxcarbazepinemonotherapyoxtellarmonohydroxy derivativeadjunctive therapy |
| spellingShingle | 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 Clinical Pharmacology: Advances and Applications oxcarbazepine monotherapy oxtellar monohydroxy derivative adjunctive therapy |
| 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_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_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_sort | predicted efficacy of once daily extended release oxcarbazepine oxtellar xr reg monotherapy in adults and children with partial onset seizures exposure response modeling and simulation |
| topic | oxcarbazepine monotherapy oxtellar monohydroxy derivative adjunctive therapy |
| url | https://www.dovepress.com/predicted-efficacy-of-once-daily-extended-release-oxcarbazepine-oxtell-peer-reviewed-article-CPAA |
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