***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: OBJECTIVE To characterize , in adolescents aged 12 - 17 , the pharmacokinetic ( PK ) profile of perampanel , the impact of intrinsic and extrinsic factors on PK , and the relationships between perampanel exposure and cognitive function , seizure frequency , and responder status . METHODS Population PK analysis used plasma concentration data from Phase II study 235 ( NCT01161524 ) , in which adolescents with inadequately controlled POS despite treatment with 1 - 3 antiepileptic drugs ( AEDs )  were r and omized to receive once daily oral placebo or perampanel ( 8 - 12mg/day ) for 19 weeks , pooled with data from adolescent patients in perampanel Phase III studies 304 , 305 , 306 . Exposure-cognition and exposure-efficacy relationships were modelled using data from study 235 . RESULTS Population PK results from 152 adolescent patients revealed a perampanel apparent clearance of 0.729L/h , consistent with previous analyses in adolescents and adults . Clearance was increased with coadministration of inducing AEDs ( carbamazepine , oxcarbazepine and phenytoin ) , and was slightly higher in females . The PK/pharmacodynamics ( PD ) analysis for cognition ( n=110 ) showed that increasing perampanel exposure had no significant effect on overall cognition , measured by the Cognitive Drug Research global cognition score . The PK/PD analysis for efficacy ( n=123 ) showed a significant decrease in seizure frequency and significant increased probability of being a responder , as perampanel concentration increased - both in the presence and absence of inducing AEDs . Carbamazepine , oxcarbazepine and phenytoin reduced perampanel exposure in adolescents , but reduced the magnitude of seizure frequency reduction and responder probability to a lesser extent . SIGNIFICANCE Pharmacokinetics of perampanel are similar in adolescents to adults . Increasing perampanel exposure reduces seizure frequency and increases probability of being a responder regardless of concomitant inducers . The lack of relationship between perampanel exposure and cognitive function suggests a benign cognitive profile for this AED in adolescents . We await results from long-term exposure To evaluate the efficacy , safety , and tolerability of perampanel , a selective , non‐competitive , α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid ( AMPA ) receptor antagonist , as an adjunctive treatment for patients with refractory partial‐onset seizures ( POS ) from Asia‐Pacific Explore perampanel pharmacokinetics ( PK ) in all subjects ( aged ≥12 years ) vs adolescents ( aged ≥12 to ≤17 years ) with partial‐onset seizures ( POS ) and identify factors explaining between‐subject variability in efficacy using a population PK/pharmacodynamic ( PD ) analysis OBJECTIVE The aim of this study was to evaluate long-term effects of adjunctive perampanel on cognition , efficacy , growth , safety , and tolerability in adolescents with inadequately controlled partial seizures . METHODS Study 235 , a multicenter , r and omized , double-blind , placebo-controlled , parallel-group , Phase II study with an open-label extension phase ( NCT01161524 ) , was primarily design ed to assess the effects of adjunctive perampanel on cognition . Patients ( aged ≥12 to < 18years ) had a diagnosis of epilepsy with inadequately controlled partial seizures , with or without secondary generalization , despite receiving 1 - 3 antiepileptic drugs . During the double-blind phase , adjunctive perampanel or placebo was administered over a 6-week titration period and a 13-week maintenance period up to 12mg/day . During the extension phase , all patients received perampanel . Data from the extension phase are presented here . Study endpoints included change from baseline in Cognitive Drug Research ( CDR ) measures of cognition , seizure frequency , growth , development , the occurrence of treatment-emergent adverse events ( TEAEs ) , and laboratory values . RESULTS A total of 114 patients entered the extension phase ( prior double-blind treatment : placebo , n=41 ; perampanel , n=73 ) . Perampanel had no effect on the CDR system global cognition score , continuity of attention , quality of episodic memory , quality of working memory , or speed of memory but was associated with a significant decline in power of attention at end of treatment compared with baseline ( p=0.03 ) . There were no effects on language skills or manual dexterity from baseline to end of treatment . At Weeks 40 - 52 , median reduction in seizure frequency was 74.1 % , and 50 % responder rate was 66.0 % . There were no clinical ly relevant effects of perampanel  on growth or development at end of treatment compared with baseline . Overall , 84.2 % of patients experienced at least one TEAE and 70.2 % experienced at least one treatment-related TEAE . The most common TEAEs were dizziness ( 29.8 % ) and somnolence ( 19.3 % ) . The TEAEs result ed in the discontinuation of treatment in 6.1 % of patients . CONCLUSIONS In keeping with the 19-week double-blind phase , long-term adjunctive treatment with perampanel did not have any significant overall effects on the CDR system global cognition score in adolescent patients with inadequately controlled partial seizures . Similar trends were observed across the individual CDR system domains . Adjunctive perampanel showed sustained long-term seizure control and had a safety and tolerability profile similar to that observed in prior clinical studies 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 ( Clinical Trials.gov identifier : NCT00699972 ) . Patients ( ≥12 years , with ongoing seizures despite 1–3 AEDs ) were r and omized ( 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 r and omized 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 Summary Objective Perampanel , a selective , noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid ( AMPA ) glutamate receptor antagonist , is indicated for adjunctive treatment of partial seizures in patients ≥12 years based on three phase III clinical studies . The perampanel U.S. Prescribing Information includes a boxed warning for serious psychiatric and behavioral adverse reactions . To provide context for this warning , detail on psychiatric and behavioral safety data from perampanel clinical studies is presented . Methods An analysis of pooled safety data from three phase III studies in patients with partial seizures is presented . Data from phase I and phase II studies in patients with and without epilepsy were also analyzed . Psychiatric and behavioral treatment‐emergent adverse events ( TEAEs ) were evaluated according to Medical Dictionary for Regulatory Activities ( MedDRA ) terms , using “ narrow ” and “ narrow‐ and ‐broad ” st and ardized MedDRA queries ( SMQs ) for TEAEs suggestive of hostility/aggression . Results From the three phase III partial‐seizure studies , the overall rate of psychiatric TEAEs was higher in the 8 mg ( 17.2 % ) and 12 mg ( 22.4 % ) perampanel groups versus placebo ( 12.4 % ) . In the “ narrow ” SMQ , hostility/aggression TEAEs were observed in 2.8 % for 8 mg and 6.3 % for 12 mg perampanel groups , versus 0.7 % of placebo patients . “ Narrow‐ and ‐broad ” SMQs for hostility/aggression TEAE rates were 12.3 % for 8 mg and 20.4 % for 12 mg perampanel groups , versus 5.7 % for placebo ; rates for events result ing in discontinuation were perampanel = 1.6 % versus placebo = 0.7 % . For events reported as serious AEs ( SAEs ) , rates were perampanel = 0.7 % versus placebo = 0.2 % . In nonepilepsy patients , psychiatric TEAEs were similar between patients receiving perampanel and placebo . In phase I subjects/volunteers , all psychiatric TEAEs were mild or moderate . These analyses suggest that psychiatric adverse effects are associated with use of perampanel . Significance Patients and caregivers should be counseled regarding the potential risk of psychiatric and behavioral events with perampanel in patients with partial seizures ; patients should be monitored for these events during treatment , especially during titration and at higher doses Assess  cognitive effects of adjunctive perampanel in adolescents PURPOSE Perampanel is one of the latest antiepileptic drugs ( AEDs ) approved for the treatment of focal and generalised epilepsy in individuals with epilepsy aged 12 years and older . There is sparse data on the use of Perampanel in children under 12 . We conducted a study amongst paediatric neurologists in the United Kingdom to investigate its effectiveness and tolerability as an adjunctive therapy in children of all ages with refractory epilepsy . METHODS Data was collected via an online question naire sent to paediatric neurologists in the UK . Data gathered , prospect i ve in 62 ( 64.5 % ) and retrospective in 34 ( 35.5 % ) patients , included changes in seizure frequency from baseline and unwanted effects at 3 , 6 and 12 months follow-up . Only patients with a minimum follow-up of six months were included . RESULTS Ninety six patients ( 48 females ) with refractory epilepsy from 11 of 29 tertiary centres were included . Median [ IQR ] ( range ) age was 14 years 11 months [ 12 years , 16 years 6 months ] ( 11 months-24 years 5 months ) . Seventy three ( 76 % ) had focal epilepsy , sixteen ( 17 % ) generalised , and seven ( 7 % ) patients both generalised and focal epilepsy . The responder rate , ≥50 % seizure reduction from baseline , was 19 % for all seizure types at both 6 and 12 months , 19 % and 24 % for focal seizures , and 25 % and 7 % for generalised seizures at these time points respectively . The retention rate was 42 % at 12 months . Treatment was discontinued due to unwanted effects in 29 ( 36.7 % ) of the 79 patients with follow-up data available up to 12 months : 30 % due to challenging behaviour , 14 % dizziness , and 7.6 % somnolence . CONCLUSION Perampanel was fairly effective in a heterogeneous group of 96 children and adolescents with very refractory epilepsy . The rate of adverse events leading to discontinuation was considerable in this group The noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid ( AMPA ) receptor antagonist perampanel was shown in phase III trials to be an effective and well‐tolerated adjunctive treatment for partial‐onset seizures . In adolescents , it is necessary to characterize cognitive , neuro 
    Output:
    
Perampanel , as an adjunctive treatment for uncontrolled focal-onset seizures , results in an improvement of seizure control with a generally good safety profile .
Higher amounts of perampanel might be required in patients taking enzyme-inducing antiepileptic drugs .
The most common adverse events are somnolence , dizziness and behavioral adverse events .
The latter seems more frequent in adolescents than in adults and in adolescents with preexisting behavioral comorbidities .
Current studies did not identify any short-term impact of perampanel on cognitive functions .
Its long half-life allows once-daily administration .
Real-life studies further established that a decrease of the dose frequently resolves adverse events , as demonstrated in pivotal studies .