PMID- 24867391
OWN - NLM
STAT- MEDLINE
DCOM- 20140922
LR  - 20220408
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 55
IP  - 7
DP  - 2014 Jul
TI  - Long-term safety of perampanel and seizure outcomes in refractory partial-onset 
      seizures and secondarily generalized seizures: results from phase III extension 
      study 307.
PG  - 1058-68
LID - 10.1111/epi.12643 [doi]
AB  - OBJECTIVE: To evaluate safety, tolerability, seizure frequency, and regional 
      variations in treatment responses with the AMPA antagonist, perampanel, in a 
      large extension study during up to 3 years of treatment. METHODS: Patients >/= 12 
      years old with partial-onset seizures despite treatment with 1-3 antiepileptic 
      drugs at baseline completed a perampanel phase III trial and entered extension 
      study 307 (NCT00735397). Patients were titrated to 12 mg/day (or their individual 
      maximum tolerated dose) during the blinded conversion period, followed by 
      open-label maintenance. Exposure, safety (adverse events [AEs], vital signs, 
      weight, electrocardiography [ECG], laboratory values) and seizure outcomes were 
      analyzed; key measures were assessed by geographic regions. RESULTS: Among 1,216 
      patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 
      patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs 
      reported in >/= 10% of patients were dizziness, somnolence, headache, fatigue, 
      irritability, and weight increase. Only dizziness and irritability caused 
      discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only 
      serious AEs reported in >1% of patients were epilepsy-related (convulsion, 3.0%; 
      status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or 
      laboratory parameters were seen. After titration/conversion, responder rate and 
      median percentage change from baseline in seizure frequency were stable: 46% for 
      both measures at 9 months (in 980 patients with >/= 9 months' exposure) and 58% and 
      60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). 
      Median percentage reduction in frequency of secondarily generalized (SG) seizures 
      ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 
      patients with maintenance data >/= 1 year, 5.3% were seizure-free for the entire 
      year. SIGNIFICANCE: No new safety signals emerged during up to 3 years of 
      perampanel exposure in 39 countries. Seizure responses remained stable, with 
      marked reductions, particularly in SG seizures.
CI  - (c) 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of 
      International League Against Epilepsy.
FAU - Krauss, Gregory L
AU  - Krauss GL
AD  - Johns Hopkins University, Baltimore, Maryland, U.S.A.
FAU - Perucca, Emilio
AU  - Perucca E
FAU - Ben-Menachem, Elinor
AU  - Ben-Menachem E
FAU - Kwan, Patrick
AU  - Kwan P
FAU - Shih, Jerry J
AU  - Shih JJ
FAU - Clement, Jean-Francois
AU  - Clement JF
FAU - Wang, Xuefeng
AU  - Wang X
FAU - Bagul, Makarand
AU  - Bagul M
FAU - Gee, Michelle
AU  - Gee M
FAU - Zhu, Jin
AU  - Zhu J
FAU - Squillacote, David
AU  - Squillacote D
LA  - eng
SI  - ClinicalTrials.gov/NCT00735397
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140527
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 0 (Nitriles)
RN  - 0 (Pyridones)
RN  - H821664NPK (perampanel)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anticonvulsants/adverse effects/*therapeutic use
MH  - Child
MH  - Double-Blind Method
MH  - Epilepsies, Partial/*diagnosis/*drug therapy/physiopathology
MH  - Epilepsy, Generalized/*diagnosis/*drug therapy/physiopathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Mental Disorders/chemically induced/diagnosis
MH  - Middle Aged
MH  - Nitriles
MH  - Pyridones/adverse effects/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4283992
OTO - NOTNLM
OT  - AMPA receptor
OT  - Antagonist
OT  - Antiepilepsy drugs
OT  - Epilepsy
OT  - Seizure freedom
EDAT- 2014/05/29 06:00
MHDA- 2014/09/23 06:00
CRDT- 2014/05/29 06:00
PHST- 2014/03/27 00:00 [accepted]
PHST- 2014/05/29 06:00 [entrez]
PHST- 2014/05/29 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
AID - 10.1111/epi.12643 [doi]
PST - ppublish
SO  - Epilepsia. 2014 Jul;55(7):1058-68. doi: 10.1111/epi.12643. Epub 2014 May 27.