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Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303

OBJECTIVE: Drug development for patients with Lennox‐Gastaut syndrome (LGS) is based on clinical trials that use drop seizure counts. However, such counts do not assess total seizure burden and affect a patient's quality of life (QoL). In this post hoc analysis, we evaluated two novel seizure e...

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Autores principales: Auvin, Stéphane, Williams, Betsy, McMurray, Rob, Kumar, Dinesh, Perdomo, Carlos, Malhotra, Manoj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546073/
https://www.ncbi.nlm.nih.gov/pubmed/31168494
http://dx.doi.org/10.1002/epi4.12314
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author Auvin, Stéphane
Williams, Betsy
McMurray, Rob
Kumar, Dinesh
Perdomo, Carlos
Malhotra, Manoj
author_facet Auvin, Stéphane
Williams, Betsy
McMurray, Rob
Kumar, Dinesh
Perdomo, Carlos
Malhotra, Manoj
author_sort Auvin, Stéphane
collection PubMed
description OBJECTIVE: Drug development for patients with Lennox‐Gastaut syndrome (LGS) is based on clinical trials that use drop seizure counts. However, such counts do not assess total seizure burden and affect a patient's quality of life (QoL). In this post hoc analysis, we evaluated two novel seizure efficacy parameters related to QoL in pediatric patients with LGS, using seizure diary data from rufinamide Study 303 (NCT01405053). METHODS: Study 303 was a phase III, multicenter, randomized, controlled, open‐label study involving patients aged ≥1 to <4 years with inadequately controlled LGS. Patients were randomized 2:1 to receive add‐on therapy with rufinamide or any other approved antiseizure drug (ASD), in addition to their existing treatment of 1‐3 ASDs, across a 106‐week treatment phase. Seizure diaries, completed by parents or caregivers, recorded seizure occurrence, and were used in this post hoc analysis to evaluate two novel efficacy parameters comparing baseline vs postbaseline mean number of seizure‐free days and assessing time to reach the number of prerandomization seizures for patients receiving rufinamide or any other ASD. RESULTS: Patients received rufinamide (n = 25) or any other ASD (n = 12). For rufinamide, mean number of seizure‐free days was 42.2% greater postbaseline compared with baseline (P < 0.0001); only one rufinamide patient experienced a decrease in number of seizure‐free days postbaseline. Median time to reach the baseline number of seizures increased by 10.5 days for rufinamide and 0.5 days for the any‐other‐ASD group during the treatment phase, to 46.0 and 54.0 days, respectively. SIGNIFICANCE: Both of these novel and contrasting endpoints demonstrated potential improvements in seizure outcomes in patients receiving rufinamide postbaseline vs baseline. Although these parameters should be investigated in larger patient populations, our initial findings suggest that they could be applied as predefined primary endpoints for seizure assessment in future clinical trials for LGS drug development.
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spelling pubmed-65460732019-06-05 Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303 Auvin, Stéphane Williams, Betsy McMurray, Rob Kumar, Dinesh Perdomo, Carlos Malhotra, Manoj Epilepsia Open Full‐length Original Research OBJECTIVE: Drug development for patients with Lennox‐Gastaut syndrome (LGS) is based on clinical trials that use drop seizure counts. However, such counts do not assess total seizure burden and affect a patient's quality of life (QoL). In this post hoc analysis, we evaluated two novel seizure efficacy parameters related to QoL in pediatric patients with LGS, using seizure diary data from rufinamide Study 303 (NCT01405053). METHODS: Study 303 was a phase III, multicenter, randomized, controlled, open‐label study involving patients aged ≥1 to <4 years with inadequately controlled LGS. Patients were randomized 2:1 to receive add‐on therapy with rufinamide or any other approved antiseizure drug (ASD), in addition to their existing treatment of 1‐3 ASDs, across a 106‐week treatment phase. Seizure diaries, completed by parents or caregivers, recorded seizure occurrence, and were used in this post hoc analysis to evaluate two novel efficacy parameters comparing baseline vs postbaseline mean number of seizure‐free days and assessing time to reach the number of prerandomization seizures for patients receiving rufinamide or any other ASD. RESULTS: Patients received rufinamide (n = 25) or any other ASD (n = 12). For rufinamide, mean number of seizure‐free days was 42.2% greater postbaseline compared with baseline (P < 0.0001); only one rufinamide patient experienced a decrease in number of seizure‐free days postbaseline. Median time to reach the baseline number of seizures increased by 10.5 days for rufinamide and 0.5 days for the any‐other‐ASD group during the treatment phase, to 46.0 and 54.0 days, respectively. SIGNIFICANCE: Both of these novel and contrasting endpoints demonstrated potential improvements in seizure outcomes in patients receiving rufinamide postbaseline vs baseline. Although these parameters should be investigated in larger patient populations, our initial findings suggest that they could be applied as predefined primary endpoints for seizure assessment in future clinical trials for LGS drug development. John Wiley and Sons Inc. 2019-03-13 /pmc/articles/PMC6546073/ /pubmed/31168494 http://dx.doi.org/10.1002/epi4.12314 Text en © 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Full‐length Original Research
Auvin, Stéphane
Williams, Betsy
McMurray, Rob
Kumar, Dinesh
Perdomo, Carlos
Malhotra, Manoj
Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303
title Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303
title_full Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303
title_fullStr Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303
title_full_unstemmed Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303
title_short Novel seizure outcomes in patients with Lennox‐Gastaut syndrome: Post hoc analysis of seizure‐free days in rufinamide Study 303
title_sort novel seizure outcomes in patients with lennox‐gastaut syndrome: post hoc analysis of seizure‐free days in rufinamide study 303
topic Full‐length Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546073/
https://www.ncbi.nlm.nih.gov/pubmed/31168494
http://dx.doi.org/10.1002/epi4.12314
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