TY - JOUR
T1 - Randomized phase III study 306 Adjunctive perampanel for refractory partial-onset seizures
AU - Krauss, G. L.
AU - Serratosa, J. M.
AU - Villanueva, V.
AU - Endziniene, M.
AU - Hong, Z.
AU - French, J.
AU - Yang, H.
AU - Squillacote, D.
AU - Edwards, H. B.
AU - Zhu, J.
AU - Laurenza, A.
N1 - Funding Information:
Study funding: This study was funded by Eisai Inc.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - Objective: To evaluate the efficacy and safety of perampanel 2, 4, and 8 mg/day added to 1-3 concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods: During this double-blind, placebo-controlled trial, patients with persisting seizures on 1-3 AEDs were randomized to perampanel 2, 4, and 8 mg/day or placebo following a 6-week baseline phase. Perampanel was titrated weekly by 2 mg/day and maintained at the dose achieved for 13 weeks. Primary endpoints were median percent change in seizure frequency and 50% responder rate. Analysis of covariance was performed on all treated patients with any seizure data (recorded in daily diaries) in the double-blind phase. Results: A total of 706 patients were randomized and received trial medication; 623 completed the trial. Median percent change in seizure frequency-the primary efficacy endpoint-was -10.7%, -13.6%, -23.3%, and -30.8% for placebo, perampanel 2, 4, and 8 mg/day, respectively. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0026) and 8 mg/day (p < 0.0001). The corresponding 50% responder rates were 17.9%, 20.6%, 28.5%, and 34.9%. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0132) and 8 mg/day (p = 0.0003). An apparent dose response was suggested for dizziness, which was the most frequent treatment-emergent adverse event. Conclusions: This trial demonstrated that adjunctive perampanel effectively reduced seizure frequency and possessed a favorable tolerability profile in patients -12 years with partial-onset seizures (with or without secondary generalization), with a minimum effective dose of 4 mg/day. Classification of Evidence: This study provides Class I evidence that 4 and 8 mg/day doses of adjunctive perampanel are effective and tolerated in reducing partial-onset seizures.
AB - Objective: To evaluate the efficacy and safety of perampanel 2, 4, and 8 mg/day added to 1-3 concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods: During this double-blind, placebo-controlled trial, patients with persisting seizures on 1-3 AEDs were randomized to perampanel 2, 4, and 8 mg/day or placebo following a 6-week baseline phase. Perampanel was titrated weekly by 2 mg/day and maintained at the dose achieved for 13 weeks. Primary endpoints were median percent change in seizure frequency and 50% responder rate. Analysis of covariance was performed on all treated patients with any seizure data (recorded in daily diaries) in the double-blind phase. Results: A total of 706 patients were randomized and received trial medication; 623 completed the trial. Median percent change in seizure frequency-the primary efficacy endpoint-was -10.7%, -13.6%, -23.3%, and -30.8% for placebo, perampanel 2, 4, and 8 mg/day, respectively. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0026) and 8 mg/day (p < 0.0001). The corresponding 50% responder rates were 17.9%, 20.6%, 28.5%, and 34.9%. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0132) and 8 mg/day (p = 0.0003). An apparent dose response was suggested for dizziness, which was the most frequent treatment-emergent adverse event. Conclusions: This trial demonstrated that adjunctive perampanel effectively reduced seizure frequency and possessed a favorable tolerability profile in patients -12 years with partial-onset seizures (with or without secondary generalization), with a minimum effective dose of 4 mg/day. Classification of Evidence: This study provides Class I evidence that 4 and 8 mg/day doses of adjunctive perampanel are effective and tolerated in reducing partial-onset seizures.
UR - http://www.scopus.com/inward/record.url?scp=84860755687&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860755687&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e318254473a
DO - 10.1212/WNL.0b013e318254473a
M3 - Article
C2 - 22517103
AN - SCOPUS:84860755687
SN - 0028-3878
VL - 78
SP - 1408
EP - 1415
JO - Neurology
JF - Neurology
IS - 18
ER -