Review of clinical studies of perampanel in adolescent patients

Kim, Heung Dong; Shiang, Ching; Desudchit, Tayard; Nikanorova, Marina; Visudtibhan, Anannit; Nabangchang, Charcrin; Chan, Derrick Wei Shih; Fong, Choong Yi; Chang, Kai Ping; Kwan, Shang Yeong; Reyes, Fe De Los; Huang, Chao; Likasitwattanakul, Surachai; Lee, Wang-Tso; Yung, Arthur; Dash, Amitabh

doi:10.1002/brb3.505

Cited by 14 publications

(7 citation statements)

References 17 publications

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“…Some of the reported increases in body weight could be a result of adolescents maturing. A previous study in adolescent patients with focal seizures showed that the mean change in weight percentile increased slightly from baseline (46.1%) to end of treatment (48.0%) following treatment with adjunctive perampanel (≤12 mg/day) but decreased slightly following treatment with placebo (49.9% to 49.1%); however, as the average weight change observed in adolescents receiving perampanel was consistent with that expected for the general adolescent population, this change can be attributed to normal adolescent growth …”

Section: Discussionsupporting

confidence: 53%

Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open‐label extension of phase III randomized trials: Study 307

et al. 2018

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SummaryObjective: To evaluate long-term safety/tolerability and seizure outcomes in patients with focal seizures treated with adjunctive perampanel in the open-label extension (OLEx) Study 307 (ClinicalTrials.gov identifier: NCT00735397). Methods: Patients could enter the OLEx after completing one of the doubleblind, phase III studies. Safety/tolerability and seizure outcomes (median percent reduction in seizure frequency per 28 days, and 50% responder and seizure freedom rates) were analyzed during the OLEx in cohorts with the same minimum perampanel exposure for all focal seizures and secondarily generalized seizures (SGS). An additional sensitivity analysis accounted for early dropouts from the OLEx. Results: Of 1480 patients randomized across the double-blind studies, 1218 enrolled in the OLEx. The majority of patients (65.4%-80.9%) received a last daily dose of perampanel 12 mg and completed long-term assessment on the same, or one fewer, concomitant antiepileptic drug compared with baseline. The long-term safety/tolerability profile was consistent with the double-blind studies.Treatment-emergent adverse events (TEAEs) leading to discontinuation in >1% of patients were dizziness, irritability, and fatigue; TEAEs of clinical interest were stable for 4 years. In all cohorts, seizure outcome improvements were sustained over time. Median percent seizure reductions per 28 days reached 62.0% and 70.6% for patients with ≥3 (n = 436) or ≥4 (n = 78) years of exposure, respectively; corresponding 50% responder rates were 59.6% and 67.9%. The largest median percent seizure reduction per 28 days occurred in SGS for patients with SGS at baseline: 88.0% and 100.0% for patients with ≥3 (n = 190) or ≥4 (n = 28) years of exposure, respectively; in these cohorts 40.0% and 53.6% of The copyright line for this article was changed on 30 March 2018 after original online publication.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: Discussionsupporting

confidence: 53%

Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open‐label extension of phase III randomized trials: Study 307

et al. 2018

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“…Efficacy: The pooled data from the three phase III studies showed improved seizure control in perampanel-treated adolescent, consistent with the overall findings in adults [29,30].…”

Section: Perampanelsupporting

confidence: 77%

Untitled

2017

Cent Asian J Med Sci

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Objectives: Up to one third of epilepsy patients have an unsatisfactory treatment with antiepileptic drugs (AEDs), but advance in neuroimaging, neurophysiologic investigation and treatment modalities have substantially improved the approaches and understanding of intractable childhood epilepsy. Methods: Journal papers, reports, books and government publications on epilepsy treatment were collected and reviewed in chronological order. Results:There are approximately more than 15 newer AEDs developed since 1990, highlighted by the novel mechanism of action with minimal adverse effect, thus they have been frequently used for those who are unresponsive to conventional AEDs. Non-pharmacologic therapies including diet therapy, epilepsy surgery, and neuromodulatory treatment are also effective and should be considered early in the disease course. Diet therapy began to reemerge in mid 1990s, and studies with large data collection allowed to overcome major concerns; its side effects, difficult compliance and doubts on efficacy. And more liberal forms of the diet therapy were introduced to benefit adults and patients in developing counties, where strict supervision is unavailable. The surgical treatment has become increasingly more valuable and it is now accepted for the management of drug resistant focal epilepsy due to major advances in presurgical investigation methods, and surgical techniques. Conclusions: The timely assessment of children with drugresistant epilepsy and active application of advanced treatment modalities were necessary to prevent the effect of uncontrolled seizures on cognitive and behavioral development.

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“…Due to its novel mechanism of action, perampanel could be considered a rational combination therapy in adolescent patients with focal seizures who have not achieved control with other AEDs . Although the tolerability profile in adolescents was generally favorable in the phase 3 trials, young patients receiving perampanel should be monitored for AEs related to irritability and aggression, particularly during dose titration and at higher doses.…”

Section: Perampanel In Clinical Practicementioning

confidence: 99%

Perampanel: Does it have broad‐spectrum potential?

Potschka

Trinka

2018

Epilepsia

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This article reviews the profile of perampanel, a novel noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist, and its role as a potential broad-spectrum antiepileptic drug in the treatment of epilepsy. For this narrative review, data were collected using specified search criteria. Articles reporting the evidence for perampanel's efficacy from preclinical models, phase 3 clinical studies, observational studies, and descriptive evidence were included. AMPA receptors play a key role in mediating the action of glutamate at the excitatory synapse. Preclinical research showed the AMPA receptor blockade to constitute a promising target for antiepileptic drug therapy. In animal models, perampanel proved to be protective against seizures and reduce seizure severity and duration. Four phase-3 randomized controlled trials (3 in patients with focal seizures and one in primary generalized tonic-clonic seizures in idiopathic generalized epilepsy) have been completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg) significantly reduced seizure frequency per 28 days (23.3%-28.8% vs 12.8%; P < .01) and responder rates (≥50% reduction in seizures) (28.5%-35.3% vs 19.3%; P < .05) compared with placebo. In primary generalized tonic-clonic seizures, perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (-76.5% vs -38.4%; P < .0001) and responder rate (64.2% vs 39.5%; P = .0019) than placebo. The efficacy, safety, and tolerability of perampanel have been reproduced in real-world clinical practice, and the agent has been shown to be effective in other epilepsy syndromes. Perampanel is a potentially broad-spectrum antiepileptic drug with a novel mechanism of action that may be a useful addition for patients with epilepsy with various seizure types. The availability of novel antiepileptic drugs for epilepsy treatment enables more individualized treatment for these patients.

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Review of clinical studies of perampanel in adolescent patients

Cited by 14 publications

References 17 publications

Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open‐label extension of phase III randomized trials: Study 307

Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open‐label extension of phase III randomized trials: Study 307

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Perampanel: Does it have broad‐spectrum potential?

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