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Francesco Bibbiani - One of the best experts on this subject based on the ideXlab platform.
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evaluation of long term safety tolerability and behavioral outcomes with adjunctive Rufinamide in pediatric patients 1 to 4 years old with lennox gastaut syndrome final results from randomized study 303
European Journal of Paediatric Neurology, 2019Co-Authors: Alexis Arzimanoglou, Dinesh Kumar, Jose Ferreira, Andrew Satlin, Omar Olhaye, Shobha Dhadda, Francesco BibbianiAbstract:Abstract Objective Evaluate the long-term safety, tolerability, and behavioral effects of adjunctive Rufinamide in pediatric patients (≥1 to Methods Study 303 (ClinicalTrials.gov identifier NCT01405053 ) was a multicenter, randomized, open-label, Phase III trial. Patients were randomized (2:1) to oral suspension Rufinamide (≤45 mg/kg/day) or any other investigator-chosen antiepileptic drug (AED) for a 2-year treatment period. Primary safety/tolerability assessments included monitoring of treatment-emergent adverse events (TEAEs) and serious TEAEs. Behavioral effects were assessed via the Child Behavior Checklist (CBCL) using the Total Problems score and change from baseline in CBCL Total Problems score. CBCL subscores were also evaluated. Results The Safety Analysis Set included 37 patients (Rufinamide: n = 25; any other AED: n = 12). TEAE incidence was similar between the Rufinamide (88.0%) and any-other-AED groups (83.3%); serious TEAE incidence was also similar between treatment groups (40.0% and 41.7%, respectively). Between treatment groups, the difference in the least squares mean CBCL Total Problems score across time was not significant (p = 0.7083), behavior outcomes were similar across all endpoints, and there were no consistent trends in CBCL subscores. Significance Long-term (2 years) adjunctive Rufinamide was well tolerated in pediatric patients with LGS. Behavioral outcomes were comparable between the Rufinamide and any-other-AED groups, however the small sample size and difficulties assessing behavior in this population should be noted. The challenges of this study raise the issue of revising how studies in very young children with rare and complex epilepsies are performed.
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efficacy and safety of adjunctive Rufinamide in lennox gastaut syndrome lgs results from studies 022 022e 303 304 and 305 p1 273
Neurology, 2018Co-Authors: Alexis Arzimanoglou, Yoko Ohtsuka, Carlos Perdomo, Betsy Williams, G Kluger, Francesco Bibbiani, A Muller, Manoj MalhotraAbstract:Objective: Present an overview of efficacy and safety for adjunctive Rufinamide in LGS patients aged 1–30 years. Background: LGS, a rare epilepsy syndrome, affects 1–4% of children with epilepsy. Limited treatment options demonstrate inadequate seizure control and unfavorable tolerability. Design/Methods: Studies 022 (Glauser et al. Neurology 2008;70:1950–1958) and 304 (Ohtsuka et al. Epilepsy Res 2014;108:1627–1636) were Phase III, double-blind, placebo-controlled studies of adjunctive Rufinamide in LGS patients aged 4–30 years (28-day Baseline; 84-day Treatment Phase). Rufinamide maintenance dose: 022, ≤45 mg/kg/day; 304, 800–3200 mg/day by body weight (15.0 to ≥70.1 kg). Patients completing 022 or 304 could enter an open-label extension (022E [Kluger et al. Acta Neurol Scand 2010;122:202–208]; 305 [Ohtsuka et al. Epilepsy Res 2016;121:1–7], respectively). The Phase III, randomized, open-label Study 303 (Arzimanoglou et al. EJPN 2016;20:393–402) assessed adjunctive Rufinamide (45 mg/kg/day) versus any-other-AED (antiepileptic drug) in patients aged 1– Results: Median percent reduction in tonic-atonic seizure frequency: 022, 42.5% Rufinamide (n=74) and −1.4% placebo (n=64; P P =0.003). Median percent reduction in total seizure frequency: 022, 32.7% Rufinamide and 11.7% placebo ( P =0.0015); 304, 32.9% and 3.1%, respectively ( P Conclusions: There were significant reductions in seizure frequencies for adjunctive Rufinamide versus placebo in LGS patients aged 4–30 years. Safety of adjunctive Rufinamide was confirmed in LGS patients aged 1– Study Supported by: Eisai Inc. Disclosure: Dr. Arzimanoglou has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, UCB, GW, Zogenix, Takeda, Shire, Upsher-Smith. Dr. Arzimanoglou has received research support from Eisai, Caixa Bank Spain, UCB. Dr. Kluger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Gerhard Kluger has served on advisory boards and received speaking honoraria from UCB Inc. and Eisai Inc. Dr. Kluger has received research support from Eisai Inc. Dr. Muller has nothing to disclose. Dr. Ohtsuka has nothing to disclose. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc. Dr. Williams holds stock and/or stock options in Spouse is employee of Stryker Orthopedics. Dr. Williams has received research support from Employee of Eisai Inc. Dr. Bibbiani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai employee. Dr. Perdomo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc. Dr. Malhotra has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc.
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dosing considerations for Rufinamide in patients with lennox gastaut syndrome phase iii trial results and real world clinical data
Seizure-european Journal of Epilepsy, 2017Co-Authors: Sanjeev V Kothare, Rajneeshkaur Sachdeo, Carlos Perdomo, Betsy Williams, G Kluger, Omar Olhaye, Francesco BibbianiAbstract:Abstract Purpose Lennox–Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, Rufinamide dosing and titration may differ from the trial setting. Here, Rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. Methods Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of Rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. Results Results demonstrated that a rapid titration schedule (7 or 14 days) of Rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic–atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study – somnolence, vomiting, and pyrexia – occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of Rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. Conclusions A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of Rufinamide in LGS.
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dosing considerations for Rufinamide in patients with lennox gastaut syndrome phase iii trial results and real world clinical data
Seizure-european Journal of Epilepsy, 2017Co-Authors: Sanjeev V Kothare, Rajneeshkaur Sachdeo, Carlos Perdomo, Betsy Williams, G Kluger, Omar Olhaye, Francesco BibbianiAbstract:Abstract Purpose Lennox–Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, Rufinamide dosing and titration may differ from the trial setting. Here, Rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. Methods Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of Rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. Results Results demonstrated that a rapid titration schedule (7 or 14 days) of Rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic–atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study – somnolence, vomiting, and pyrexia – occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of Rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. Conclusions A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of Rufinamide in LGS.
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response durability analyses from a Rufinamide pivotal trial in lennox gastaut syndrome lgs p2 043
Neurology, 2016Co-Authors: Yutze Ng, Tracy A Glauser, Carlos Perdomo, Betsy Williams, Omar Olhaye, J M F Ferreira, Francesco BibbianiAbstract:Objective: Many antiepileptic drugs (AEDs) have been reported to lose efficacy during prolonged treatment.1 This analysis examines response durability with Rufinamide. Background: Rufinamide is a triazole derivative, structurally unrelated to other AEDs, approved for adjunctive treatment of seizures associated with LGS in patients aged ≥1year. Design/Methods: Subjects with LGS were aged 4-37 years, taking fixed-dose regimens of 1-3 concomitant AEDs. Following prospective baseline (28 days), subjects were randomized to a double-blind phase (Titration=14 days; Maintenance=70 days) and received Rufinamide (45mg/kg/day maximum dose) or placebo. Subjects completing the double-blind phase were eligible for the open-label extension (OLE), which lasted up to 3 years; all subjects received adjunctive Rufinamide treatment. Patients who received placebo during the double-blind phase started conversion on ~10mg ⁄kg ⁄day Rufinamide. This was gradually up-titrated to a total dosage of ~25-60mg ⁄kg ⁄day. Outcomes included response durability for total seizures and tonic-atonic (drop attack) seizures. Results: 138 subjects were randomized and treated (Rufinamide=74; placebo=64) during the double-blind phase, and 124 subjects entered the OLE. For both total and tonic-atonic seizures, larger median decreases in seizure frequency/28 days were observed as early as 2 weeks and over the course of treatment for Rufinamide (total: -20.6[percnt]−-43.1[percnt]; tonic-atonic: -22.8[percnt]−-50.3[percnt]) than for placebo (total: 1.3[percnt]−-1.5[percnt]; tonic-atonic: -1.3[percnt]−1.0[percnt]), suggesting a fast onset of action and lack of short-term tolerance to Rufinamide. During the OLE, Rufinamide efficacy continued up to 3 years as exhibited by the progressive median decreases in seizure frequency/28 days over the course of open-label treatment from 3 to 36 months (3 years) for total seizures (-31.6[percnt]−-79.3[percnt]) and tonic-atonic seizures (-41.9[percnt]−-76.1[percnt]). Conclusions: There was no evidence of tolerance to Rufinamide during short-term and long-term treatment. These data support adjunctive Rufinamide treatment for multiple seizure types, which may enhance patient adherence. Refs:1Loscher.Epilepsia2006;47:1253-84. Support: Eisai Inc. Disclosure: Dr. Ng has nothing to disclose. Dr. Glauser has received (royalty or license fee or contractual rights) payments from AssureRx Health. Dr. Ferreira has received personal compensation for activities with Eisai Inc. Dr. Olhaye has received personal compensation for activities with Eisai Inc., as an employee. Dr. Williams has received personal compensation for activities with Eisai Inc. as an employee. Mr. Perdomo has received personal compensation for activities with Eisai Inc., as an employee. Dr. Bibbiani has received personal compensation for activities with Eisai Inc. as an employee.
Carlos Perdomo - One of the best experts on this subject based on the ideXlab platform.
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novel seizure outcomes in patients with lennox gastaut syndrome post hoc analysis of seizure free days in Rufinamide study 303
Epilepsia open, 2019Co-Authors: Stephane Auvin, Rob Mcmurray, Carlos Perdomo, Dinesh Kumar, Betsy Williams, Manoj MalhotraAbstract: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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efficacy and safety of adjunctive Rufinamide in lennox gastaut syndrome lgs results from studies 022 022e 303 304 and 305 p1 273
Neurology, 2018Co-Authors: Alexis Arzimanoglou, Yoko Ohtsuka, Carlos Perdomo, Betsy Williams, G Kluger, Francesco Bibbiani, A Muller, Manoj MalhotraAbstract:Objective: Present an overview of efficacy and safety for adjunctive Rufinamide in LGS patients aged 1–30 years. Background: LGS, a rare epilepsy syndrome, affects 1–4% of children with epilepsy. Limited treatment options demonstrate inadequate seizure control and unfavorable tolerability. Design/Methods: Studies 022 (Glauser et al. Neurology 2008;70:1950–1958) and 304 (Ohtsuka et al. Epilepsy Res 2014;108:1627–1636) were Phase III, double-blind, placebo-controlled studies of adjunctive Rufinamide in LGS patients aged 4–30 years (28-day Baseline; 84-day Treatment Phase). Rufinamide maintenance dose: 022, ≤45 mg/kg/day; 304, 800–3200 mg/day by body weight (15.0 to ≥70.1 kg). Patients completing 022 or 304 could enter an open-label extension (022E [Kluger et al. Acta Neurol Scand 2010;122:202–208]; 305 [Ohtsuka et al. Epilepsy Res 2016;121:1–7], respectively). The Phase III, randomized, open-label Study 303 (Arzimanoglou et al. EJPN 2016;20:393–402) assessed adjunctive Rufinamide (45 mg/kg/day) versus any-other-AED (antiepileptic drug) in patients aged 1– Results: Median percent reduction in tonic-atonic seizure frequency: 022, 42.5% Rufinamide (n=74) and −1.4% placebo (n=64; P P =0.003). Median percent reduction in total seizure frequency: 022, 32.7% Rufinamide and 11.7% placebo ( P =0.0015); 304, 32.9% and 3.1%, respectively ( P Conclusions: There were significant reductions in seizure frequencies for adjunctive Rufinamide versus placebo in LGS patients aged 4–30 years. Safety of adjunctive Rufinamide was confirmed in LGS patients aged 1– Study Supported by: Eisai Inc. Disclosure: Dr. Arzimanoglou has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, UCB, GW, Zogenix, Takeda, Shire, Upsher-Smith. Dr. Arzimanoglou has received research support from Eisai, Caixa Bank Spain, UCB. Dr. Kluger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Gerhard Kluger has served on advisory boards and received speaking honoraria from UCB Inc. and Eisai Inc. Dr. Kluger has received research support from Eisai Inc. Dr. Muller has nothing to disclose. Dr. Ohtsuka has nothing to disclose. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc. Dr. Williams holds stock and/or stock options in Spouse is employee of Stryker Orthopedics. Dr. Williams has received research support from Employee of Eisai Inc. Dr. Bibbiani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai employee. Dr. Perdomo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc. Dr. Malhotra has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc.
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dosing considerations for Rufinamide in patients with lennox gastaut syndrome phase iii trial results and real world clinical data
Seizure-european Journal of Epilepsy, 2017Co-Authors: Sanjeev V Kothare, Rajneeshkaur Sachdeo, Carlos Perdomo, Betsy Williams, G Kluger, Omar Olhaye, Francesco BibbianiAbstract:Abstract Purpose Lennox–Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, Rufinamide dosing and titration may differ from the trial setting. Here, Rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. Methods Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of Rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. Results Results demonstrated that a rapid titration schedule (7 or 14 days) of Rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic–atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study – somnolence, vomiting, and pyrexia – occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of Rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. Conclusions A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of Rufinamide in LGS.
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dosing considerations for Rufinamide in patients with lennox gastaut syndrome phase iii trial results and real world clinical data
Seizure-european Journal of Epilepsy, 2017Co-Authors: Sanjeev V Kothare, Rajneeshkaur Sachdeo, Carlos Perdomo, Betsy Williams, G Kluger, Omar Olhaye, Francesco BibbianiAbstract:Abstract Purpose Lennox–Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, Rufinamide dosing and titration may differ from the trial setting. Here, Rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. Methods Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of Rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. Results Results demonstrated that a rapid titration schedule (7 or 14 days) of Rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic–atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study – somnolence, vomiting, and pyrexia – occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of Rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. Conclusions A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of Rufinamide in LGS.
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response durability analyses from a Rufinamide pivotal trial in lennox gastaut syndrome lgs p2 043
Neurology, 2016Co-Authors: Yutze Ng, Tracy A Glauser, Carlos Perdomo, Betsy Williams, Omar Olhaye, J M F Ferreira, Francesco BibbianiAbstract:Objective: Many antiepileptic drugs (AEDs) have been reported to lose efficacy during prolonged treatment.1 This analysis examines response durability with Rufinamide. Background: Rufinamide is a triazole derivative, structurally unrelated to other AEDs, approved for adjunctive treatment of seizures associated with LGS in patients aged ≥1year. Design/Methods: Subjects with LGS were aged 4-37 years, taking fixed-dose regimens of 1-3 concomitant AEDs. Following prospective baseline (28 days), subjects were randomized to a double-blind phase (Titration=14 days; Maintenance=70 days) and received Rufinamide (45mg/kg/day maximum dose) or placebo. Subjects completing the double-blind phase were eligible for the open-label extension (OLE), which lasted up to 3 years; all subjects received adjunctive Rufinamide treatment. Patients who received placebo during the double-blind phase started conversion on ~10mg ⁄kg ⁄day Rufinamide. This was gradually up-titrated to a total dosage of ~25-60mg ⁄kg ⁄day. Outcomes included response durability for total seizures and tonic-atonic (drop attack) seizures. Results: 138 subjects were randomized and treated (Rufinamide=74; placebo=64) during the double-blind phase, and 124 subjects entered the OLE. For both total and tonic-atonic seizures, larger median decreases in seizure frequency/28 days were observed as early as 2 weeks and over the course of treatment for Rufinamide (total: -20.6[percnt]−-43.1[percnt]; tonic-atonic: -22.8[percnt]−-50.3[percnt]) than for placebo (total: 1.3[percnt]−-1.5[percnt]; tonic-atonic: -1.3[percnt]−1.0[percnt]), suggesting a fast onset of action and lack of short-term tolerance to Rufinamide. During the OLE, Rufinamide efficacy continued up to 3 years as exhibited by the progressive median decreases in seizure frequency/28 days over the course of open-label treatment from 3 to 36 months (3 years) for total seizures (-31.6[percnt]−-79.3[percnt]) and tonic-atonic seizures (-41.9[percnt]−-76.1[percnt]). Conclusions: There was no evidence of tolerance to Rufinamide during short-term and long-term treatment. These data support adjunctive Rufinamide treatment for multiple seizure types, which may enhance patient adherence. Refs:1Loscher.Epilepsia2006;47:1253-84. Support: Eisai Inc. Disclosure: Dr. Ng has nothing to disclose. Dr. Glauser has received (royalty or license fee or contractual rights) payments from AssureRx Health. Dr. Ferreira has received personal compensation for activities with Eisai Inc. Dr. Olhaye has received personal compensation for activities with Eisai Inc., as an employee. Dr. Williams has received personal compensation for activities with Eisai Inc. as an employee. Mr. Perdomo has received personal compensation for activities with Eisai Inc., as an employee. Dr. Bibbiani has received personal compensation for activities with Eisai Inc. as an employee.
G Kluger - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of adjunctive Rufinamide in lennox gastaut syndrome lgs results from studies 022 022e 303 304 and 305 p1 273
Neurology, 2018Co-Authors: Alexis Arzimanoglou, Yoko Ohtsuka, Carlos Perdomo, Betsy Williams, G Kluger, Francesco Bibbiani, A Muller, Manoj MalhotraAbstract:Objective: Present an overview of efficacy and safety for adjunctive Rufinamide in LGS patients aged 1–30 years. Background: LGS, a rare epilepsy syndrome, affects 1–4% of children with epilepsy. Limited treatment options demonstrate inadequate seizure control and unfavorable tolerability. Design/Methods: Studies 022 (Glauser et al. Neurology 2008;70:1950–1958) and 304 (Ohtsuka et al. Epilepsy Res 2014;108:1627–1636) were Phase III, double-blind, placebo-controlled studies of adjunctive Rufinamide in LGS patients aged 4–30 years (28-day Baseline; 84-day Treatment Phase). Rufinamide maintenance dose: 022, ≤45 mg/kg/day; 304, 800–3200 mg/day by body weight (15.0 to ≥70.1 kg). Patients completing 022 or 304 could enter an open-label extension (022E [Kluger et al. Acta Neurol Scand 2010;122:202–208]; 305 [Ohtsuka et al. Epilepsy Res 2016;121:1–7], respectively). The Phase III, randomized, open-label Study 303 (Arzimanoglou et al. EJPN 2016;20:393–402) assessed adjunctive Rufinamide (45 mg/kg/day) versus any-other-AED (antiepileptic drug) in patients aged 1– Results: Median percent reduction in tonic-atonic seizure frequency: 022, 42.5% Rufinamide (n=74) and −1.4% placebo (n=64; P P =0.003). Median percent reduction in total seizure frequency: 022, 32.7% Rufinamide and 11.7% placebo ( P =0.0015); 304, 32.9% and 3.1%, respectively ( P Conclusions: There were significant reductions in seizure frequencies for adjunctive Rufinamide versus placebo in LGS patients aged 4–30 years. Safety of adjunctive Rufinamide was confirmed in LGS patients aged 1– Study Supported by: Eisai Inc. Disclosure: Dr. Arzimanoglou has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, UCB, GW, Zogenix, Takeda, Shire, Upsher-Smith. Dr. Arzimanoglou has received research support from Eisai, Caixa Bank Spain, UCB. Dr. Kluger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Gerhard Kluger has served on advisory boards and received speaking honoraria from UCB Inc. and Eisai Inc. Dr. Kluger has received research support from Eisai Inc. Dr. Muller has nothing to disclose. Dr. Ohtsuka has nothing to disclose. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc. Dr. Williams holds stock and/or stock options in Spouse is employee of Stryker Orthopedics. Dr. Williams has received research support from Employee of Eisai Inc. Dr. Bibbiani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai employee. Dr. Perdomo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc. Dr. Malhotra has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc.
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dosing considerations for Rufinamide in patients with lennox gastaut syndrome phase iii trial results and real world clinical data
Seizure-european Journal of Epilepsy, 2017Co-Authors: Sanjeev V Kothare, Rajneeshkaur Sachdeo, Carlos Perdomo, Betsy Williams, G Kluger, Omar Olhaye, Francesco BibbianiAbstract:Abstract Purpose Lennox–Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, Rufinamide dosing and titration may differ from the trial setting. Here, Rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. Methods Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of Rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. Results Results demonstrated that a rapid titration schedule (7 or 14 days) of Rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic–atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study – somnolence, vomiting, and pyrexia – occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of Rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. Conclusions A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of Rufinamide in LGS.
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dosing considerations for Rufinamide in patients with lennox gastaut syndrome phase iii trial results and real world clinical data
Seizure-european Journal of Epilepsy, 2017Co-Authors: Sanjeev V Kothare, Rajneeshkaur Sachdeo, Carlos Perdomo, Betsy Williams, G Kluger, Omar Olhaye, Francesco BibbianiAbstract:Abstract Purpose Lennox–Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, Rufinamide dosing and titration may differ from the trial setting. Here, Rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. Methods Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of Rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. Results Results demonstrated that a rapid titration schedule (7 or 14 days) of Rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic–atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study – somnolence, vomiting, and pyrexia – occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of Rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. Conclusions A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of Rufinamide in LGS.
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current role of Rufinamide in the treatment of childhood epilepsy literature review and treatment guidelines
European Journal of Paediatric Neurology, 2014Co-Authors: Giangennaro Coppola, Marina Nikanorova, Frank M C Besag, Raffaella Cusmai, O Dulac, G Kluger, Romina Moavero, Rima Nabbout, Francesco Pisani, Alberto VerrottiAbstract:Abstract Purpose The literature on the efficacy and safety of Rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of Rufinamide in the treatment of childhood epilepsies. Results Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that Rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs. Conclusion Rufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on Rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined.
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low long term efficacy and tolerability of add on Rufinamide in patients with dravet syndrome
Epilepsy & Behavior, 2011Co-Authors: A Mueller, Pasquale Striano, Giangennaro Coppola, Rainer Boor, M Dahlin, C Von Stuelpnagel, J Lotte, M Staudt, G KlugerAbstract:Abstract In this retrospective European multicenter study we evaluated the efficacy and tolerability of Rufinamide in patients with Dravet syndrome and refractory seizures. Twenty patients were included; in 16 patients a SCN1A mutation was detected. The responder rate after 6 months was 20%, and after 34 months, 5%. The retention rate was 45% after 6 months and 5% after 34 months. Rufinamide treatment was stopped because of aggravation of seizures (30%), no effect (45%), and side effects (10%). The efficacy and long-term retention rate were low in our patients with Dravet syndrome and refractory seizures, far lower than in patients with Lennox–Gastaut syndrome; one-third of our patients experienced seizure aggravation. Therefore, Rufinamide does not seem to be a suitable option for long-term treatment in patients with Dravet syndrome.
Rob Mcmurray - One of the best experts on this subject based on the ideXlab platform.
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novel seizure outcomes in patients with lennox gastaut syndrome post hoc analysis of seizure free days in Rufinamide study 303
Epilepsia open, 2019Co-Authors: Stephane Auvin, Rob Mcmurray, Carlos Perdomo, Dinesh Kumar, Betsy Williams, Manoj MalhotraAbstract: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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Rufinamide for the treatment of Lennox-Gastaut syndrome: evidence from clinical trials and clinical practice
Epileptic Disorders, 2018Co-Authors: Pasquale Striano, Rob Mcmurray, Estevo Santamarina, Mercè FalipAbstract:: Rufinamide was granted orphan drug status in 2004 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients aged ≥4 years, and was subsequently approved for this indication in several countries, including Europe and the United States. Structurally unrelated to other antiepileptic drugs, Rufinamide is thought to act primarily by prolonging the inactivation phase of voltage-gated sodium channels. Rufinamide was approved on the basis of an international, randomised, placebo-controlled Phase III trial, conducted in 138 patients with Lennox-Gastaut syndrome, which demonstrated its favourable tolerability profile and efficacy in significantly reducing the frequency of drop attacks and total seizures, compared with placebo. The effectiveness and safety/tolerability of Rufinamide in treating seizures associated with Lennox-Gastaut syndrome have subsequently been confirmed in several other clinical trials and long-term extension studies. These findings are supported by 'real-world' data from a series of clinical practice studies conducted in Europe, the United States, and Korea. Rufinamide has been shown to be effective and generally well tolerated in children as young as one year and in adults. It is particularly effective as treatment for drop attacks and generalised tonic-clonic seizures, and it has been suggested that it might be preferred over other antiepileptic drugs as a second-line treatment for Lennox-Gastaut syndrome when drop attacks are frequent. The most common side effects of Rufinamide treatment include somnolence, headache, dizziness, nausea, vomiting, and fatigue. No new or unexpected safety signals have emerged following long-term treatment with Rufinamide, either in clinical trials or in clinical practice.
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real world data on Rufinamide treatment in patients with lennox gastaut syndrome results from a european noninterventional registry study
Epilepsy & Behavior, 2017Co-Authors: Marina Nikanorova, Stephane Auvin, Christian Brandt, Rob McmurrayAbstract:Abstract Introduction Rufinamide is approved for the adjunctive treatment of seizures associated with Lennox–Gastaut syndrome (LGS) in patients aged ≥ 4 years. The objective of this study was to provide real-world, long-term data on patients with LGS initiating Rufinamide as add-on therapy and patients with LGS receiving other antiepileptic drugs (AEDs). Methods A Phase IV, noninterventional, multicenter registry study was conducted in patients with LGS aged ≥ 4 years requiring modification to any AED treatment, including initiation of add-on Rufinamide therapy. Safety/tolerability was assessed by evaluating treatment-emergent adverse events (TEAEs), and efficacy was assessed using a generic seizure frequency scale. Results A total of 111 patients from 64 sites in 8 European countries were included, of whom 64 initiated Rufinamide (“Rufinamide” group) and 21 did not receive Rufinamide at any time during the study (“no-Rufinamide” group). Mean ages were 16.1 years (Rufinamide) and 15.0 years (no Rufinamide). The median duration of follow-up was > 2 years (range: 1.3–46.4 months). Antiepileptic drug-related TEAEs were reported for 40.6% (Rufinamide) and 33.3% (no Rufinamide) of patients and led to discontinuation of 7.8% and 4.8%, respectively. The most frequently reported Rufinamide-related TEAEs (≥ 5% patients) were somnolence (7.8%) and decreased appetite (6.3%). There were no unexpected safety/tolerability findings. At month 12, the proportion of patients with improvement in all seizures (“much improved” or “very much improved”) was 28.6% (12/42) for the Rufinamide group and 14.3% (2/14) for the no-Rufinamide group. Conclusion The study provided valuable information on LGS and its management, and evidence that Rufinamide has a consistent and generally favorable safety/tolerability profile when used in routine clinical practice. ClinicalTrials.Gov identifier NCT01991041
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Treatment of Adults with Lennox–Gastaut Syndrome: Further Analysis of Efficacy and Safety/Tolerability of Rufinamide
Neurology and Therapy, 2016Co-Authors: Rob Mcmurray, Pasquale StrianoAbstract:Introduction Management of Lennox–Gastaut syndrome (LGS) in adulthood can be particularly challenging. Published reports describing the use of Rufinamide specifically in adult patients with LGS are scarce. A post hoc subgroup analysis of data from a phase III trial was conducted to investigate the efficacy and safety/tolerability of Rufinamide in adults with LGS. Methods A randomized, double-blind, placebo-controlled trial was conducted in patients with LGS, aged 4 years and above. During an 84-day, double-blind treatment period, patients received either adjunctive Rufinamide therapy or placebo. Efficacy and safety/tolerability were assessed in a post hoc subgroup analysis of adult patients (≥18 years). Efficacy was assessed as change from baseline in 28-day seizure frequency, 50% responder rate, and seizure freedom rate; each calculated for total seizures and drop attacks. Safety/tolerability assessments included the evaluation of adverse events (AEs). Results Thirty-one adults aged 18–37 years with LGS received treatment with either Rufinamide ( n = 21) or placebo ( n = 10). Three patients in the Rufinamide group did not complete the trial. The median change from baseline in seizure frequency was −31.5% for Rufinamide versus +22.1% for placebo ( P = 0.008) for all seizures and −54.9% versus +21.7% ( P = 0.002) for drop attacks. Responder rates were 33.3% for Rufinamide versus 0% for placebo ( P = 0.066) for all seizures and 57.1% versus 10.0% ( P = 0.020) for drop attacks. No patient achieved freedom from all seizures but two Rufinamide-treated patients (9.5%) became free of drop attacks. Overall, 71.4% of patients treated with Rufinamide and 60.0% of patients treated with placebo experienced AEs; most commonly, somnolence (33.3% vs. 20.0%) and vomiting (19.0% vs. 0%). Most AEs were of mild or moderate intensity. Conclusion Rufinamide demonstrated favorable efficacy and was generally well tolerated when used as adjunctive treatment for adults with LGS. Funding Eisai.
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efficacy of Rufinamide as adjunctive treatment for adults with lennox gastaut syndrome subgroup analysis from a phase iii trial p2 056
Neurology, 2016Co-Authors: Pasquale Striano, Rob McmurrayAbstract:Objective: A post-hoc subgroup analysis of data from a Phase III trial was conducted to investigate the efficacy of Rufinamide in adults with Lennox Gastaut Syndrome (LGS). Background: Rufinamide is a triazole derivative, structurally unrelated to other antiepileptic drugs, approved for adjunctive treatment of seizures associated with LGS in patients aged ≥1 years. LGS often persists into adulthood, or may have late-onset in adulthood.1 Management of LGS in adulthood is challenging; seizures are often intractable and most patients have moderate to severe cognitive impairment.1 Design/Methods: A randomized, double-blind, placebo-controlled trial was conducted in patients with LGS, aged 437 years, with history of multiple seizures types (including tonic-atonic and atypical absence seizures) and a minimum of 90 seizures prior to the 28-day Baseline period. During a 14-day Titration phase plus 70-day Maintenance period, patients received double-blind treatment with either Rufinamide (titrated to ~45 mg/kg/day maximum) or placebo. Efficacy in adult patients (≥18 years) was assessed as median percentage change from baseline per 28 days of all seizures and tonic-atonic seizures during double-blind treatment. Results: Adults with LGS were randomized to adjunctive treatment with Rufinamide (n=21; 15 Male, 6 Female) or placebo (n=10; 5M, 5F). Mean (standard deviation [SD]; range) age was 25.2 (4.7; 1835) and 29.3 (7.1; 1837) years in the Rufinamide and placebo groups, respectively; mean (SD; range) time since LGS diagnosis was 18.5 (8.9; 033) and 25.5 (8.1; 834) years, respectively. Median change from baseline in seizure frequency was -31.5[percnt] for Rufinamide versus +22.1[percnt] for placebo (p=0.008, Wilcoxon Rank-Sum test, unadjusted) for all seizures and -54.9[percnt] versus +21.7[percnt] (p=0.002), respectively, for tonic-atonic seizures. Conclusions: Rufinamide demonstrated favourable efficacy, compared with placebo, when used as adjunctive treatment for adults with LGS. Ref: 1Arzimanoglou et al. Lancet.2009;8(1):82-93. Support: Eisai Inc. Disclosure: Dr. Striano has received personal compensation for activities with Shire Pharma and Eisai Inc. Dr. McMurray has received personal compensation for activities with Eisai Ltd. as an employee.
Kuniaki Iyoda - One of the best experts on this subject based on the ideXlab platform.
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long term safety and seizure outcome in japanese patients with lennox gastaut syndrome receiving adjunctive Rufinamide therapy an open label study following a randomized clinical trial
Epilepsy Research, 2016Co-Authors: Yoko Ohtsuka, Harumi Yoshinaga, Rumiko Takayama, Hiroki Takano, Yukiyoshi Shirasaka, Kuniaki IyodaAbstract:Abstract Purpose To evaluate the long-term safety and seizure outcome in Japanese patients with Lennox–Gastaut syndrome (LGS) receiving adjunctive Rufinamide therapy. Subjects and methods We conducted an open-label extension study following a 12-week multicenter, randomized, double-blind, placebo-controlled study of adjunctive Rufinamide therapy in Japanese patients with LGS. Fifty-four patients participated in the extension study. Seizure frequency was evaluated until 52 weeks after the start of the extension study. Adverse events (AEs) were evaluated throughout both studies. Key findings Of the 54 patients, 41 (75.9%) completed the extension study. The median duration of exposure to Rufinamide was 818.0 days in all 54 patients, and 38 patients (70.4%) received Rufinamide for 2 years or more. The median percent change in the frequency of tonic–atonic seizures relative to the frequency at the start of the double-blind study was −39.3% (12 weeks), −40.6% (24 weeks), −46.8% (32 weeks), −47.6% (40 weeks), and −36.1% (52 weeks). Reduction of total seizure frequency was also maintained until 52 weeks. Frequent treatment-related AEs were somnolence (20.4%), decreased appetite (16.7%), transient seizure aggravation including status epilepticus (13.0%), vomiting (11.1%), and constipation (11.1%). Adverse events were mild or moderate, except for transient seizure aggravation in three patients. Adverse events resulting in discontinuation of Rufinamide were decreased appetite, drug eruption, and worsening of underlying autism. When clinically notable weight loss was defined as a decrease ≥7% relative to baseline, 22 patients (40.7%) experienced weight loss at least once during long-term observation, although weight loss was reported as an AE in only three patients. Significance This study demonstrated a long-term benefit of Rufinamide as adjunctive therapy for Japanese patients with LGS. Exacerbation of seizures and decreased appetite/weight loss should be monitored carefully.
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Long-term safety and seizure outcome in Japanese patients with Lennox–Gastaut syndrome receiving adjunctive Rufinamide therapy: An open-label study following a randomized clinical trial
Epilepsy Research, 2016Co-Authors: Yoko Ohtsuka, Harumi Yoshinaga, Rumiko Takayama, Hiroki Takano, Yukiyoshi Shirasaka, Kuniaki IyodaAbstract:Abstract Purpose To evaluate the long-term safety and seizure outcome in Japanese patients with Lennox–Gastaut syndrome (LGS) receiving adjunctive Rufinamide therapy. Subjects and methods We conducted an open-label extension study following a 12-week multicenter, randomized, double-blind, placebo-controlled study of adjunctive Rufinamide therapy in Japanese patients with LGS. Fifty-four patients participated in the extension study. Seizure frequency was evaluated until 52 weeks after the start of the extension study. Adverse events (AEs) were evaluated throughout both studies. Key findings Of the 54 patients, 41 (75.9%) completed the extension study. The median duration of exposure to Rufinamide was 818.0 days in all 54 patients, and 38 patients (70.4%) received Rufinamide for 2 years or more. The median percent change in the frequency of tonic–atonic seizures relative to the frequency at the start of the double-blind study was −39.3% (12 weeks), −40.6% (24 weeks), −46.8% (32 weeks), −47.6% (40 weeks), and −36.1% (52 weeks). Reduction of total seizure frequency was also maintained until 52 weeks. Frequent treatment-related AEs were somnolence (20.4%), decreased appetite (16.7%), transient seizure aggravation including status epilepticus (13.0%), vomiting (11.1%), and constipation (11.1%). Adverse events were mild or moderate, except for transient seizure aggravation in three patients. Adverse events resulting in discontinuation of Rufinamide were decreased appetite, drug eruption, and worsening of underlying autism. When clinically notable weight loss was defined as a decrease ≥7% relative to baseline, 22 patients (40.7%) experienced weight loss at least once during long-term observation, although weight loss was reported as an AE in only three patients. Significance This study demonstrated a long-term benefit of Rufinamide as adjunctive therapy for Japanese patients with LGS. Exacerbation of seizures and decreased appetite/weight loss should be monitored carefully.
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Rufinamide as an adjunctive therapy for lennox gastaut syndrome a randomized double blind placebo controlled trial in japan
Epilepsy Research, 2014Co-Authors: Yoko Ohtsuka, Harumi Yoshinaga, Rumiko Takayama, Hiroki Takano, Yukiyoshi Shirasaka, Kuniaki IyodaAbstract:Summary Purpose To evaluate the efficacy, safety, and pharmacokinetics of Rufinamide as an adjunctive therapy for patients with Lennox–Gastaut syndrome (LGS) in a randomized, double-blind, placebo-controlled trial. Methods We conducted a multicenter clinical trial with a 4-week baseline, a 2-week titration, a 10-week maintenance, and either a follow-up visit or entry into an open-label extension. Patients with LGS (4 to 30 years old) taking between one and three antiepileptic drugs were recruited. After the baseline period, patients were randomly assigned to Rufinamide or placebo. The primary efficacy variable was the percent change in the tonic–atonic seizure frequency per 28 days. Key findings Of the 59 patients, 29 were randomized to the Rufinamide group and 30 to the placebo group. The frequency of epileptic seizures was significantly decreased in the Rufinamide group than in the placebo group; the median percent change in frequency of tonic–atonic seizures was −24.2% and −3.3%, respectively, ( p =0.003) and that of total seizures was −32.9% and −3.1%, respectively ( p Significance The present results showed a favorable risk-benefit profile for Rufinamide as an adjunctive therapy for patients with LGS.
