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Adjunctive perampanel for refractory partial-onset seizures : randomized phase III study 304 . OBJECTIVE To assess efficacy and safety of once-daily 8 or 12 mg perampanel , a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid ( AMPA ) receptor antagonist , when added to concomitant antiepileptic drugs ( AEDs ) in the treatment of drug-resistant partial-onset seizures . METHODS This was a multicenter , double-blind , placebo-controlled trial ( ClinicalTrials.gov identifier : NCT00699972 ) . Patients ( ≥12 years , with ongoing seizures despite 1-3 AEDs ) were randomized ( 1:1:1 ) to once-daily perampanel 8 mg , 12 mg , or placebo . Following baseline ( 6 weeks ) , patients entered a 19-week double-blind phase : 6-week titration ( 2 mg/week increments to target dose ) followed by a 13-week maintenance period . Percent change in seizure frequency was the primary endpoint ; 50 % responder rate was the primary endpoint for EU registration . RESULTS Of 388 patients randomized and treated , 387 provided seizure frequency data . Using this intent-to-treat population over the double-blind phase , the median percent change in seizure frequency was -21.0 % , -26.3 % , and -34.5 % for placebo and perampanel 8 and 12 mg , respectively ( p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo , respectively ) . Fifty percent responder rates during the maintenance period were 26.4 % , 37.6 % , and 36.1 % , respectively , for placebo , perampanel 8 mg , and perampanel 12 mg ; these differences were not statistically significant for 8 mg ( p = 0.0760 ) or 12 mg ( p = 0.0914 ) . Sixty-eight ( 17.5 % ) patients discontinued , including 40 ( 10.3 % ) for adverse events . Most frequent treatment-emergent adverse events were dizziness , somnolence , irritability , headache , fall , and ataxia . CONCLUSIONS This trial demonstrated that once-daily , adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures . Doses of perampanel 8 and 12 mg were safe , and tolerability was acceptable . CLASSIFICATION OF EVIDENCE This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures .
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Intervention_Pharmacological
perampanel
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Intervention_Pharmacological
perampanel
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Outcome_Physical
the median percent change in seizure frequency
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Outcome_Adverse-effects
were dizziness , somnolence , irritability , headache , fall , and ataxia
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Outcome_Physical
improved seizure control