Efficacy Of Adjunctive Perampanel Research Articles

Efficacy and Safety of adjunctive Perampanel in a prospective, real-world, Phase IV study in Indian patients aged ≥12 years for Treatment of focal-onset Epilepsy: Study 508.

ESPRITE (Study 508; NCT03836924) evaluated the real-world safety, tolerability, and efficacy of adjunctive perampanel in patients aged ≥12 years with focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), in India. ESPRITE was a prospective, multicenter, single-arm, observational, Phase IV study with a 6-month Treatment Period. Patients were aged ≥12 years and had been prescribed perampanel for adjunctive treatment of FOS, with or without FBTCS. Assessments included incidence of treatment-emergent adverse events (TEAEs; primary endpoint), median percent reduction in seizure frequency per 28 days from baseline, 50% responder rates, and seizure-freedom rates. Overall, 200 patients were enrolled (199 patients in the Safety Analysis Set and 174 patients who completed all visits in the main efficacy analyses). TEAEs (all mild or moderate in severity) were reported in 18.1% (n = 36/199) of patients (the most common were dizziness [3.0%] and irritability [2.0%]). TEAEs leading to discontinuation of perampanel were reported in 2.0% of patients; no deaths or serious TEAEs occurred. At 6 months, median percent reduction in seizure frequency was 100.0%, 50% responder rate was 83.3%, and seizure-freedom rate was 49.4%. Adjunctive perampanel (at a mean daily dose of 4 mg/day) was shown to be well tolerated and effective in patients aged ≥12 years with FOS, with or without FBTCS, from India. Many patients do not receive adequate treatment for epilepsy and need effective seizure control medications. In this 6-month clinical study, 199 patients from India, aged 12 years or older, added perampanel to the anti-seizure medications they were already taking. At 6 months, 49% of patients experienced no seizures since starting perampanel and seizure frequency was reduced by half in 83% of patients. Side effects occurred in 18% of patients (most commonly dizziness and irritability) and caused 2% to stop perampanel; no deaths were reported. Perampanel was an effective and generally safe added medication for patients with epilepsy from India.

Efficacy and Safety of Perampanel in Children with Drug-Resistant Focal-Onset Seizures: A Retrospective Review

Background: Epilepsy is one of the most common neurological disorders. Existing antiseizure medications (ASMs) are still unable to control seizures in one-third of these patients, making the discovery of antiseizure therapies with novel mechanisms of action a necessity. Aim of the Study: This study aimed to determine the safety and efficacy of perampanel (PER) as an adjuvant treatment for children with drug-resistant focal-onset seizures with or without focal to bilateral tonic-clonic seizures. Patients and methods: This is a single-center retrospective study of 38 epileptic pediatric patients, aged 2 to 14, at King Faisal Specialist Hospital and Research Center whose seizures were pharmaco-resistant to more than two antiseizure medications and followed for at least three months after PER adjuvant therapy initiation. Efficacy was assessed by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and side effects were also reported. Results: Multiple seizure types were reported. Myoclonic seizures were the predominant type of epilepsy in 17 children (44.7%). At 3 months, 6 months, and 12 months of follow-up, approximately 23.4%, 23.4%, and 18.4% of the patients were seizure-free at these time points, respectively. Adverse events were documented in 14 patients (35.7%) and led to the discontinuation of PER in 26.3%, 31.6%, and 36.8% of the studied group at the 3-, 6-, and 12-month follow-ups, respectively. The most common adverse events included dizziness or drowsiness, irritability, gait disturbance, and confusion; however, all were transient, and no serious adverse effects occurred. Conclusion: Our findings confirm the therapeutic efficacy of adjunctive PER in the treatment of drug-resistant epilepsy in children. As an adjunctive treatment for epilepsy, perampanel demonstrated sufficient effectiveness and tolerability.

Effectiveness and tolerability of adjunctive perampanel in the treatment of pediatric patients with uncontrolled epilepsy: A retrospective, single-center, real-world study

ObjectiveThe main aim of this study was to assess the efficacy, safety, and tolerability of adjunctive perampanel (PER) in the treatment of children and adolescents with epilepsy. MethodsPediatric patients who visited the pediatric epilepsy clinic of Henan Provincial People’s Hospital between May 2020 and December 2021 were recruited. All participants were treated with PER as adjunctive therapy and were seen routinely (minimum: a baseline and 12-week visit). The efficacy and tolerability of adjunctive PER for the treatment of epilepsy were investigated. ResultsOne hundred and fourteen patients were enrolled, among whom 7 (6.1%) were lost to follow-up. At 12 weeks, the responder rate and the seizure-free rate were 56.1% (60/107) and 32.7% (35/107), respectively. The responder rate increased with the duration of PER administration and was significantly higher when PER was used as an early add-on (after ≤2 prior antiseizure medications (ASMs)) than a late add-on (after >2 prior ASMs). However, there was no significant difference in the treatment efficacy of adjunctive PER in patients with different epilepsy etiologies or types. Adverse events, including irritability, dizziness, somnolence, ataxic gait, weight gain, and tinnitus, were reported in thirty-two patients (29.9%). ConclusionsIn a routine clinical setting of pediatric patients with epilepsy, good effectiveness and tolerability of adjunctive PER were demonstrated. Notably, patients initiating PER as an early add-on showed a better seizure outcome than those initiating PER as a late add-on.

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

Open‐label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic‐clonic seizures

ObjectiveStudy 311 (NCT02849626) was a global, multicenter, open‐label, single‐arm study that assessed safety, tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics of once‐daily adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with focal seizures (FS) (with/without focal to bilateral tonic‐clonic seizures [FBTCS]) or generalized tonic‐clonic seizures (GTCS).MethodsIn the 311 Core Study, a 4‐week Pre‐treatment Period (Screening/Baseline) preceded a 23‐week Treatment Period (11‐week Titration; 12‐week Maintenance) and 4‐week Follow‐up. Endpoints included safety/tolerability (primary endpoint), median percent change in seizure frequency per 28 days from Baseline (Treatment Period), and 50% responder and seizure‐freedom rates (Maintenance Period). Patients were stratified by age (4 to <7; 7 to <12 years) and concomitant enzyme‐inducing anti‐seizure drug (EIASD) use.ResultsOne hundred eighty patients were enrolled (FS, n = 149; FBTCS, n = 54; GTCS, n = 31). The Core Study was completed by 146 patients (81%); the most common primary reason for discontinuation was adverse event (AE) (n = 14 [8%]). Mean (standard deviation) daily perampanel dose was 7.0 (2.6) mg/day and median (interquartile range) duration of exposure was 22.9 (2.0) weeks. The overall incidence of treatment‐emergent AEs (TEAEs; 89%) was similar between patients with FS (with/without FBTCS) and GTCS. The most common TEAEs were somnolence (26%) and nasopharyngitis (19%). There were no clinically important changes observed for cognitive function, laboratory, or electrocardiogram (ECG) parameters or vital signs. Median percent reductions in seizure frequency per 28 days from Baseline were as follows: 40% (FS), 59% (FBTCS), and 69% (GTCS). Corresponding 50% responder and seizure‐freedom rates were as follows: FS, 47% and 12%; FBTCS, 65% and 19%; and GTCS, 64% and 55%, respectively. Improvements in response/seizure frequency from Baseline were seen regardless of age or concomitant EIASD use.SignificanceResults from the 311 Core Study suggest that daily oral doses of adjunctive perampanel are generally safe, well tolerated, and efficacious in children age 4 to <12 years with FS (with/without FBTCS) or GTCS.

Effect of Concomitant Enzyme-Inducing Antiepileptic Drugs (EIAEDs) on the Safety and Efficacy of Adjunctive Perampanel in Patients Aged 4 to &lt;12 years with Partial-Onset Seizures (POS): Final Results from the 311 Core Study (P3.5-007)

Effect of Concomitant Enzyme-Inducing Antiepileptic Drugs (EIAEDs) on the Safety and Efficacy of Adjunctive Perampanel in Patients Aged 4 to &lt;12 years with Partial-Onset Seizures (POS): Final Results from the 311 Core Study (P3.5-007)

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): Final Results from the 311 Core Study (P3.5-001)

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): Final Results from the 311 Core Study (P3.5-001)

Safety and Efficacy of Adjunctive Perampanel in Younger (aged 4 to &lt;7 years) and Older (7 to &lt;12 years) Pediatric Patients with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS): Final Results from the 311 Core Study (P1.5-021)

Safety and Efficacy of Adjunctive Perampanel in Younger (aged 4 to &lt;7 years) and Older (7 to &lt;12 years) Pediatric Patients with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS): Final Results from the 311 Core Study (P1.5-021)

Long-term tolerability, safety and efficacy of adjunctive perampanel in the open-label, dose-ascending Study 231 and extension Study 233 in Japanese patients with epilepsy

PurposeTo evaluate long-term tolerability, safety and efficacy of adjunctive perampanel in a Phase II, multicentre, open-label, dose-ascending Study 231 (NCT00849212) and its extension (Study 233; NCT00903786) in Japanese patients with refractory partial-onset seizures (POS), with/without secondarily generalised seizures. MethodsIn Study 231, patients received adjunctive perampanel ≤12 mg/day during a 10-week treatment period. Patients completing Study 231 could enter Study 233 (≤316-week treatment period). Assessments included monitoring of treatment-related treatment-emergent adverse events (TEAEs), median percent change in seizure frequency per 28 days, 50% responder and seizure-freedom rates. During Study 231, a pharmacokinetic analysis assessed the effects of enzyme-inducing antiepileptic drugs. ResultsOverall, 23/30 (76.7%) patients completed Study 231; 21/30 (70.0%) received perampanel ≥8 mg/day and 10/30 (33.3%) achieved a maximum tolerated dose of 12 mg/day. Median percent change in seizure frequency per 28 days was –35.0%. 50% responder rate was 37.0%; 4 (13.3%) patients achieved seizure freedom. Twenty-one patients entered Study 233. Mean duration of exposure was 195 weeks; 9 (42.9%) patients received perampanel for ≤208 weeks. Seizure control was sustained for 316 weeks in 3/21 (14.3%) patients; 2 achieved seizure freedom. Treatment-related TEAEs were tolerable; the most common was dizziness (Study 231, 53.3%; Study 233, 14.3%). Mean perampanel plasma concentrations were lower with concomitant carbamazepine vs non-inducers (152.7 ng/mL vs 389.4 ng/mL across perampanel groups); small patient numbers for non-inducers (n = 2) should be considered when interpreting these data. ConclusionAdjunctive perampanel demonstrated a favourable safety profile and long-term tolerability in Japanese patients with refractory POS for ≤316 weeks.

Efficacy of Adjunctive Perampanel in Idiopathic Generalized Epilepsy Patients with Drug-Resistant Primary Generalized Tonic-Clonic Seizures by Age, Sex, and Race: Double-Blind Placebo-Controlled Phase III Study (P2.021)

Efficacy of Adjunctive Perampanel in Idiopathic Generalized Epilepsy Patients with Drug-Resistant Primary Generalized Tonic-Clonic Seizures by Age, Sex, and Race: Double-Blind Placebo-Controlled Phase III Study (P2.021)

Perampanel Study 207: long-term open-label evaluation in patients with epilepsy

Evaluate interim long-term tolerability, safety and efficacy of adjunctive perampanel, a novel α-amino-3-hydroxy-5-methyl-5-isoxazolepropionic acid (AMPA)-receptor antagonist, in patients with refractory partial-onset seizures. Study 207, an open-label extension (OLE) study (ClinicalTrials.gov identifier: NCT00368472), enrolled patients (18-70years) who completed one of two randomized, placebo-controlled, dose-escalation Phase II studies. The OLE Treatment Phase comprised a 12-week Titration Period (2mg increments of perampanel every 2weeks to 12mg/day, maximum) and a Maintenance Period, during which patients continued treatment up to a planned maximum of 424weeks (~8years). Interim analysis data cut-off date was 1 December, 2010. Of 180 patients completing the Phase II studies, 138 enrolled in study 207. At the time of interim analyses (approximately 4years after study start), over a third (n=53, 38.4%) remained on perampanel; 41.3% (n=57) of patients had >3years of exposure; and 13.0% (n=18) had at least 4years' exposure. Mean±standard deviation (SD) duration of exposure was 116±75weeks and mean±SD dose during the OLE Maintenance Period was 7.3±3.3mg. No new safety signals emerged with long-term treatment. Consistent with previous studies, the most common treatment-emergent adverse events were as follows: dizziness, headache and somnolence. Overall median (range) per cent change from baseline in seizure frequency per 28days during open-label treatment was -31.5% (-99.2 to 512.2). Long-term - up to 4years - adjunctive perampanel had a favourable tolerability profile in patients with refractory partial-onset seizures. Improvements in seizure control were maintained with long-term treatment.

Efficacy of Adjunctive Perampanel in Phase III Clinical Trials: Subanalysis of Change in Seizure Frequency and Responder Rates by Concomitant Antiepileptic Drug Use (S56.006)

Objective: Assess effect of concomitant antiepileptic drugs (AEDs) on seizure frequency and responder rate in a pooled analysis of perampanel phase III studies. Background In phase III trials, adjunctive perampanel was efficacious in reducing uncontrolled partial-onset seizures (4-12 mg/day). Design/Methods: Following Baseline, patients (≥12 years, receiving 1-3 AEDs) were randomized to once-daily double-blind treatment with placebo or perampanel 2, 4, 8, or 12 mg. Efficacy endpoints were analyzed with respect to concomitant use of the most frequently taken AEDs (in any combination) to test if addition of these AEDs with other mechanisms of action affected the efficacy of perampanel. Endpoints analyzed were: percent change in seizure frequency/28 days (Double-blind Phase vs Baseline) and 50% responder rate (Maintenance vs Baseline). Results: Across the phase III studies, 1478 patients were randomized and treated (placebo, n=441; perampanel 2 mg, n=180; 4 mg, n=172; 8 mg, n=431; 12 mg, n=254), and were taking an average of 2.2 concomitant AEDs. The most common AEDs (≥45 patients/treatment group), used in combinations of 1-3 concomitant AEDs, were: carbamazepine (n=491), valproate (n=478), lamotrigine (n=457), and levetiracetam (n=435). Median differences (Hodges-Lehmann) in median percent change in seizure frequency/28 days in patients receiving concomitant AED combinations including carbamazepine, valproate, lamotrigine, or levetiracetam compared with placebo ranged from: 7.7% to -7.8% with perampanel 2 mg; -3.0% to -12.7% with 4 mg; -8.9% to -20.8% with 8 mg; and -12.4% to -16.7% with 12 mg. Responder rate ranges for these patients were: 13.6-23.1% with placebo; 13.8-21.4% with perampanel 2 mg; 19.6-34.7% with 4 mg; 29.7-38.3% with 8 mg; and 30.6-43.0% with 12 mg. Conclusions: Perampanel (4-12 mg/day) decreased seizure frequency and increased responder rates in patients concomitantly taking at least one of the four most common AEDs. The presence of another AED mechanism did not appear to reduce the efficacy of perampanel. Supported by: Eisai Inc. Disclosure: Dr. French has nothing to disclose. Dr. Ben-Menachem has received personal compensation for activities with Eisai Inc, UCB Pharma, Cyberonics, Inc., GlaxoSmithKline, Inc. and Lundbeck Research USA as an advisory board participant and/or speaker. Dr. Ben-Menachem has received personal compensation in an editorial capacity for Acta Neurologica Scandinovica. Dr. Ben-Menachem has received research support from Eisai Inc, UCB Pharma and Bial. Dr. Brodie has received personal compensation for activities with Pfizer Inc, UCB Pharma, Eisai Inc., GlaxoSmithKline, Inc., Sanofi-Aventis Pharmaceuticals, Inc., and Lundbeck Research USA, Inc. Dr. Brodie has received research support from Eisai Inc. Dr. Squillacote has received personal compensation for activities with Eisai as an employee. Dr. Yang has received personal compensation for activities with Eisai, Inc. as an employee. Dr. Kumar has received personal compensation for activities with Eisai Inc. as an employee. Dr. Laurenza has received personal compensation for activities with Eisai as an employee.