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


METHODS
Study 207, an open-label extension (OLE) study (ClinicalTrials.gov identifier: NCT00368472), enrolled patients (18-70 years) who completed one of two randomized, placebo-controlled, dose-escalation Phase II studies. The OLE Treatment Phase comprised a 12-week Titration Period (2 mg increments of perampanel every 2 weeks to 12 mg/day, maximum) and a Maintenance Period, during which patients continued treatment up to a planned maximum of 424 weeks (~8 years). Interim analysis data cut-off date was 1 December, 2010.


RESULTS
Of 180 patients completing the Phase II studies, 138 enrolled in study 207. At the time of interim analyses (approximately 4 years after study start), over a third (n = 53, 38.4%) remained on perampanel; 41.3% (n = 57) of patients had >3 years of exposure; and 13.0% (n = 18) had at least 4 years' exposure. Mean ± standard deviation (SD) duration of exposure was 116 ± 75 weeks and mean ± SD dose during the OLE Maintenance Period was 7.3 ± 3.3 mg. 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 28 days during open-label treatment was -31.5% (-99.2 to 512.2).


CONCLUSIONS
Long-term - up to 4 years - adjunctive perampanel had a favourable tolerability profile in patients with refractory partial-onset seizures. Improvements in seizure control were maintained with long-term treatment.
Brno Epilepsy Centre, First Department of Neurology, St Anne's University Hospital, Masaryk University, Brno, Czech Republic. irektor@med.muni.cz
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Rektor
G L
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Krauss
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Bar
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Biton
J A
JA
Klapper
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Vaiciene-Magistris
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Kuba
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Squillacote
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Gee
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Kumar
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011728:Pyridones / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel