Primary Generalized Tonic-clonic Seizures Research Articles

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Safety and Efficacy of XEN1101 as an Adjunctive Therapy in the Treatment of Primary Generalized Tonic-Clonic Seizures (P11-1.012)

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Safety and Efficacy of XEN1101 as an Adjunctive Therapy in the Treatment of Primary Generalized Tonic-Clonic Seizures (P11-1.012)

Deregulation of Astroglial TASK-1 K+ Channel Decreases the Responsiveness to Perampanel-Induced AMPA Receptor Inhibition in Chronic Epilepsy Rats

Tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid sensitive K+-1 channel (TASK-1) is activated under extracellular alkaline conditions (pH 7.2-8.2), which are upregulated in astrocytes (particularly in the CA1 region) of the hippocampi of patients with temporal lobe epilepsy and chronic epilepsy rats. Perampanel (PER) is a non-competitive α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) antagonist used for the treatment of focal seizures and primary generalized tonic-clonic seizures. Since AMPAR activation leads to extracellular alkaline shifts, it is likely that the responsiveness to PER in the epileptic hippocampus may be relevant to astroglial TASK-1 regulation, which has been unreported. In the present study, we found that PER ameliorated astroglial TASK-1 upregulation in responders (whose seizure activities were responsive to PER), but not non-responders (whose seizure activities were not responsive to PER), in chronic epilepsy rats. ML365 (a selective TASK-1 inhibitor) diminished astroglial TASK-1 expression and seizure duration in non-responders to PER. ML365 co-treatment with PER decreased spontaneous seizure activities in non-responders to PER. These findings suggest that deregulation of astroglial TASK-1 upregulation may participate in the responsiveness to PER, and that this may be a potential target to improve the efficacies of PER.

Eslicarbazepine Acetate as Adjunctive Therapy for Primary Generalized Tonic-Clonic Seizures in Adults: A Prospective Observational Study.

BackgroundEslicarbazepine acetate (ESL), a novel sodium channel blocker, is approved for mono and adjunctive treatment of partial epileptic seizures with or without secondary generalization. Its efficacy in primary generalized seizures has not yet been evaluated.ObjectiveTo evaluate the efficacy and safety of ESL in primary generalized tonic-clonic seizures (PGTCS) in an observational study.MethodsThe data were collected from a prospective population-based register. Effectiveness was measured as relative reduction in standardized seizure frequency (SSF), responder rate (≥ 50% reduction in SSF), and seizure freedom rate at 6 and 12 months after initiation of ESL. Safety and tolerability were evaluated using patients’ diaries.ResultsFifty-six adult patients with PGTCS were treated with ESL as adjunctive therapy. Of these, 30.4% (n = 17) had myoclonic seizures in addition to PGTCS. The retention rate after 12 months was 80.4% (n = 45). After initiating ESL therapy, reduction in SSF for PGTCS on ESL was 56.0% after 6 months and 56.9% after 12 months (p < 0.01), whereas myoclonic seizures did not show any significant improvement in frequency. The responder rate for PGTCS was 64.3% after 6 months and 66.1% after 12 months, and seizure freedom was achieved in 32.1% and 35.7%, respectively. Forty-three patients (73.2%) reported no side effects. Among the reported side effects of ESL therapy, headache (7.1%), dizziness (8.9%), tiredness (7.1%), nausea (5.4%), and hyponatremia (5.4%) were the most prevalent.ConclusionsOur data suggest that ESL may provide additional benefits in the treatment of patients with PGTCS and motivate randomized controlled trials in this indication.

A Systematic Review of the Cost-effectiveness of Perampanel in the Treatment of Epilepsy

A Systematic Review of the Cost-effectiveness of Perampanel in the Treatment of Epilepsy

156 Long-term effects of perampanel on cognition, growth/development in paediatric patients with epilepsy study 311

BackgroundThe long-term (≤1-year) effects of adjunctive perampanel on cognition, behaviour and growth/development were assessed in paediatric patients aged 4–&lt;12 years with partial-onset seizures (POS) (with/without secondarily generalised seizures [SGS]) or primary generalised tonic-clonic seizures (PGTCS) during Study 311 (NCT02849626).MethodsCore Study (4-week pretreatment/23-week treatment) completers could enter the Extension (29-week maintenance/4-week follow-up). Assessments included: change from baseline at Week 52 for cognition (Aldenkamp-Baker Neuropsychological Assessment Schedule [ABNAS]), behavioural/emotional problems (Child Behaviour Checklist [CBCL]), visuomotor skills (Lafayette Grooved Pegboard Test [LGPT]) and growth/development.ResultsMean standard deviation (SD) change from baseline to Week 52 in total ABNAS score was -3.3 (16.6) (n=112). Mean (SD) change from baseline at Week 52 in CBCL total problems was -6.0 (14.0) and-1.6 (14.7) for patients aged 1.5–5 (n=17) and 6–18 years (n=102), respectively; for time to complete the LGPT, this was 5.3 (48.0) seconds for patients aged ≤8 years (n=33) and 0.4 (23.2) for patients aged &gt;8 years (n=51). No significant impact on growth/development observed.ConclusionNo clinically significant changes were observed in cognition, behaviour or growth/devel- opment parameters following long-term (≤1 year) adjunctive perampanel in paediatric patients (aged 4–&lt;12 years) with POS, SGS or PGTCS. Funding: Eisai Inc.manoj_malhotra@eisai.com

160 Long-term cognitive effects of perampanel in paediatric patients with epilepsy by responder status and dose

BackgroundThe long-term (≤1-year) effects of adjunctive perampanel on cognition by responder status and modal dose were assessed in paediatric patients (aged 4–&lt;12 years) with partial-onset seizures (with/without secondarily generalised seizures) or primary generalised tonic-clonic seizures during Study 311 (NCT02849626).MethodsCore Study (4-week pretreatment/23-week treatment) completers could enter the Extension (29-week maintenance/4-week follow-up). The Aldenkamp-Baker Neuropsychological Assessment Schedule [ABNAS] was used to assess cognition (change from baseline, Weeks 23/52) by total seizure response category (&lt;50%/≥50%/≥75%/100% responder) and modal dose (mg/day).ResultsMean (standard deviation) change from baseline in total ABNAS for Weeks 23 and 52 by response category was: &lt;50%, 3.7 (11.5) and -3.2 (16.8); ≥50%, -4.7 (13.8) and -3.7 (18.4); ≥75%, -2.1 (11.4) and -4.2(14.8); 100%, -1.6 (18.3) and -0.6 (20.6), respectively; and by modal dose was: &lt;4 mg/day, -5.8 (7.3) and-2.0 (7.2); 4 mg/day, -4.8 (22.4) and -10.4 (25.6); &gt;4–6 mg/day, 1.3 (8.3) and -1.3 (10.2); &gt;6–8 mg/day, -0.5(10.7) and 1.9 (9.4); &gt;8–12 mg/day, -0.1 (12.8) and -7.4 (20.2); &gt;12–16 mg/day, 2.2 (12.4) and 1.1 (14.8), respectively.ConclusionAdjunctive perampanel had few long-term effects on cognition in paediatric patients, regard- less of responder status and modal dose.FundingEisai Inc.11m2anoj_malhotra@eisai.com

Perampanel in the additional therapy of focal and primary generalized tonic-clonic seizures in children 4–12 years old: clinical data, experience of use and practical recommendations

On March 18, 2021, an online council of experts in the field of epilepsy treatment was held, dedicated to the use of perampanel in the additional therapy of focal seizures (FS) and primary generalized tonic-clonic seizures (PGTCS) in children 4–12 years old. During the event, the features of the use of perampanel in this group of patients were discussed, considering the specifics of everyday clinical practice, current possibilities of PGTCS and FS therapy in children, its goals, as well as unsolved problems in the treatment of pediatric patients with PGTCS and FS. Particular attention was paid to the role of perampanel in the treatment of PGTCS and FS in children and its effectiveness in specific types of focal seizures.

Health State Utility Values in Paediatric Subjects with Partial Onset Seizures (POS) or Primary Generalized Tonic Clonic Seizures (PGTCS) receiving Adjunctive Perampanel (4217)

Health State Utility Values in Paediatric Subjects with Partial Onset Seizures (POS) or Primary Generalized Tonic Clonic Seizures (PGTCS) receiving Adjunctive Perampanel (4217)

Long-Term (1-Year) Seizure Freedom with Adjunctive Perampanel in Pediatric Patients (Aged 4–&lt;12 Years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS): Post Hoc Analysis of Study 311 (1328)

Long-Term (1-Year) Seizure Freedom with Adjunctive Perampanel in Pediatric Patients (Aged 4–&lt;12 Years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS): Post Hoc Analysis of Study 311 (1328)

Long-Term (1-Year) Evaluation of Adjunctive Perampanel on Mental Health in Pediatric Patients (Aged 4–&lt;12 Years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) in Study 311 (1304)

Long-Term (1-Year) Evaluation of Adjunctive Perampanel on Mental Health in Pediatric Patients (Aged 4–&lt;12 Years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) in Study 311 (1304)

ELEVATE Study 410 Initial Results: Phase IV Study of Perampanel as Monotherapy or First Adjunctive Therapy in Patients Aged ≥4 Years with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) (1392)

ELEVATE Study 410 Initial Results: Phase IV Study of Perampanel as Monotherapy or First Adjunctive Therapy in Patients Aged ≥4 Years with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) (1392)

Health-related quality of life in pediatric patients with partial onset seizures or primary generalized tonic-clonic seizures receiving adjunctive perampanel

RationaleStudy 311 (E2007-G000-311; NCT02849626) was a Phase 3, multicenter, open-label single-arm study of adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with partial-onset seizures (POS) (with/without secondarily generalized tonic-clonic seizures [SGTCS]) or primary generalized tonic-clonic seizures (PGTCS). Health-related quality of life (HRQoL) was an exploratory endpoint initially analyzed through simple descriptive summaries. The aim of this post hoc analysis was to provide a more thorough assessment of HRQoL. MethodsThis analysis focused on EQ-5D-Y data collected at Baseline, Week 23, and Week 52. Individual dimensions, visual analog scale (VAS) and summed misery index (MI) were evaluated at all visits and compared by seizure type (POS versus SGTCS versus PGTCS), age (4 to <7 versus 7 to <12), and use of concomitant enzyme-inducing antiepileptic drugs (EIAEDs) (yes versus no). Paretian Classification of Health Change (PCHC) analysis summarized the proportion of patients who showed improvement or deterioration in HRQoL. Waterfall plots assessed changes in EQ-5D-Y scores by treatment-emergent adverse events (TEAEs) and by reduction in seizure frequency. Health state utility values associated with differing seizure frequency states were estimated using a linear mixed model. ResultsOne hundred and fifteen patients completed EQ-5D-Y at relevant study visits (Seizure type: POS n = 84 [of which 21 had SGTCS], PGTCS n = 31; Age: 4 to <7 years n = 30, 7 to <12 years n = 85; Concomitant EIAEDs: Yes n = 35, No n = 80). Completion rates out of those expected to complete EQ-5D-Y were high at both timepoints (84.4% at Week 23 and 97.2% at Week 52). Overall, VAS/MI remained stable over time (did not exceed minimal important difference); this was similar according to seizure type, age, and EIAED usage. In patients with ‘no problems’ on any EQ-5D-Y dimension at Baseline, nearly all retained their full health at Week 23 (94.7%), and all retained it at Week 52 (100.0%). PCHC analysis showed fewer patients with POS experienced deterioration in EQ-5D-Y than patients with PGTCS at Week 23 (24.1% versus 42.1%). Not experiencing a TEAE, or remaining seizure-free, was associated with improvements in VAS score at Week 23 compared to those experiencing TEAEs or seizures, respectively. Health state utility values (HSUVs) were estimated as follows: seizure free (LS Mean 0.914 [95% CIs 0.587, 1.240]), ≥1 seizure per year (0.620 [0.506, 0.734]), ≥1 seizure per month (0.596 [0.338, 0.855]), ≥1 seizure per week (0.284 [−0.014, 0.582]). ConclusionsAn in-depth analysis of EQ-5D-Y data allowed for a more nuanced exploration of HRQoL than previous descriptive summaries. Our findings provide evidence that perampanel as adjunctive therapy did not result in deterioration of patient HRQoL. The association between TEAEs or remaining seizure-free and HRQoL warrants further exploration. Increasing seizure frequency was associated with decreasing HSUVs; these can inform cost-effectiveness modeling of perampanel and other therapies aiming to reduce seizure frequency in pediatric patients.

Ligational and biological studies of Fe(III), Co(II), Ni(II), Cu(II), and Zr(IV) complexes with carbamazepine as antiepileptic drug

Carbamazepine (CBZ) is considered to be the preferred drug for fractional seizures and may also use in the prevention of primary generalized tonic–clonic seizures. The chelates of CBZ with Fe(III), Co(II), Ni(II), Cu(II), and Zr(IV) were designed and characterized on the basis of elemental analysis, FT‐IR, 1H NMR, UV‐visible, mass spectra, thermal analysis (TG, DTG, and DTA), molar conductivity, and magnetic moment. IR spectra emphasize that CBZ acts as a neutral bidentate ligand with metal ions through amide oxygen and amino nitrogen. UV‐visible spectra and magnetic moment demonstrate that all chelates have geometric octahedral structures. Complexes thermal behavior is systematically analyzed employing TG and DTA technicality. TG findings signalize that water molecules (hydrated and coordinated) are extracted the first and second phases, while CBZ ligand is splitted in the second and subsequent steps. From the DTA curves, the obtained data reflect that the degradation processes are endothermic or exothermic peaks. Assorted thermodynamic factors are calculated, and the results are explicated. Antimicrobial activity was examined against two Gram‐positive bacteria (Staphylococcus aureusand Bacillus subtilis) and two Gram‐negative bacteria (Escherichia coliandPseudomonas aeuroginosa). Anti‐fungal efficacy of the compounds has been tested. The Co(II) complex was highly significant against the antifungalCandida albicansand significantly againstEscherichia coli,Staphylococcus aureus, andBacillus subtilis.

Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomised, placebo-controlled trial

ObjectiveTo evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic...

Real-world hospitalization risk in patients with epilepsy treated with perampanel

AimThe aim of this study was to evaluate the risk of hospitalization and emergency department admission following initiation of perampanel treatment in patients with epilepsy. MethodsThis study is a retrospective longitudinal cohort study (Optum® Clinformatics® Datamart). Patients 4 to 11 years of age with a diagnosis of partial onset seizures or ≥12 years of age with primary generalized tonic–clonic seizures who had ≥1 perampanel prescription between 1/1/2014 and 3/31/2018 were eligible for the study. Additionally, patients were required to have 12-months of continuous enrollment before (pre-) and after (post-) the date of the first perampanel prescription (index-date). One-year relative-risks of all-cause and epilepsy-related hospitalizations and emergency department (ED) visits were estimated following initiation of perampanel treatment. Outcomes were also evaluated among a subsets of patients who were adherent to perampanel treatment, defined as a Medication Possession Ratio (MPR) ≥80%. ResultsA total of 320 patients were included in the study, mean age 38.2 ± 19 years, 56.6% female. In the overall population, the relative risks of hospitalizations or ED visits after perampanel initiation were not significantly different. Among the 145 patients who had an MPR ≥80%, initiation of perampanel treatment resulted in a significantly lower risk of epilepsy-related hospitalization (relative risk [RR] = 0.68, confidence interval [CI] [0.47, 0.98]), all-cause ED visits (RR = 0.80, CI [0.66, 0.98]), and epilepsy-related ED visits (RR = 0.74, CI [0.57, 0.95]) in the follow-up period. ConclusionsAdherence to perampanel treatment was associated with significant reductions in one-year hospitalizations and ED visit risk in real world settings.

Long-term Safety and Efficacy of Adjunctive Perampanel in Pediatric Patients (Aged 4 to &lt;12 years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) in Study 311 (413)

Long-term Safety and Efficacy of Adjunctive Perampanel in Pediatric Patients (Aged 4 to &lt;12 years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) in Study 311 (413)

Efficacy and Safety of Adjunctive Perampanel in South Korean Patients with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS): Post Hoc Analysis of Phase II and III Double-Blind and Open-Label Extension (OLEx) Studies (1325)

Efficacy and Safety of Adjunctive Perampanel in South Korean Patients with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS): Post Hoc Analysis of Phase II and III Double-Blind and Open-Label Extension (OLEx) Studies (1325)

Efficacy and Safety of Adjunctive Perampanel 4 mg/day in Pediatric Patients (Aged 4 to &lt;12 Years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) in Study 311 (4134)

Efficacy and Safety of Adjunctive Perampanel 4 mg/day in Pediatric Patients (Aged 4 to &lt;12 Years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) in Study 311 (4134)

Post Hoc Univariate and Multivariate Analyses to Identify Clinical Factors Associated with a 50% or 75% Response in a Phase III Trial of Adjunctive Perampanel in Patients with Primary Generalized Tonic-Clonic Seizures (PGTCS) (1834)

Post Hoc Univariate and Multivariate Analyses to Identify Clinical Factors Associated with a 50% or 75% Response in a Phase III Trial of Adjunctive Perampanel in Patients with Primary Generalized Tonic-Clonic Seizures (PGTCS) (1834)

Meta-analysis of drug efficacy in adult vs pediatric trials of patients with PGTC seizures.

ObjectiveA meta-analysis of published studies was performed to determine whether the efficacy of antiseizure drugs in adults with primary generalized tonic-clonic seizures (PGTCS) is comparable with that in the pediatric population (2–12 years of age).MethodsElectronic searches were conducted in EMBASE, Medline, and the Cochrane Central Register of Controlled Trials for clinical trials of PGTCS in adults and children 2–12 years of age. Neurologists used standardized search and study evaluations to select eligible trials. Median percent reduction in seizure frequency from baseline and ≥50% responder rates were used to compare drug efficacy in adults and children.ResultsAmong 7 adjunctive-therapy PGTCS trials in adults and children (2–12 years of age) that met evaluation criteria, effect sizes were consistent between adults and children for lamotrigine and topiramate. The baseline-subtracted median percent seizure reduction in seizure frequency ranged from 50.0% to 79.7% in children and 57.0% to 64.0% in adults. The ≥50% responder rate was similar between children and adults in a topiramate study (50% in children compared with 58% in adults).ConclusionsThis meta-analysis supports the use of drug response from antiseizure drug clinical trials for PGTCS in adults to predict comparable treatment response in children 2–12 years of age with PGTCS.