Randomized phase III study 306

• DOI: 10.1212/wnl.0b013e318254473a
• Publication Date: 2012-04-20T00:31:33Z
• Authors: G.L. Krauss; J.M. Serratosa; V. Villanueva; M. Endziniene; Z. Hong; J. French; H. Yang; D. Squillacote; H.B. Edwards; J. Zhu; A. Laurenza; Samuel Berkovic; Wendyl D'Souza; Terence O'Brien; Udaya Seneviratne; Martin Robinson; Plamen Bozinov; Ivan Milanov; Ekaterina Titianova; Zahari Zahariev; Liwen Wu; Xuefeng Wang; Dong Zhou; Jindriska Buresova; Jan Hadac; Petr Marusic; Hana Oslejskova; Sulev Haldre; Ain Pajos; Valentin Sander; Inga Talvik; Stephan Arnold; Andreas Hufnagel; Frank Kerling; Holger Lerche; Soheyl Noachtar; Felix Rosenow; Joachim Springub; Bernhard J Steinhoff; Konrad J Werhahn; Raymond T Cheung; Patrick Kwan; Ping Wing Ng; John Chan; Attila Balogh; István Kondákor; Magdolna Neuwirth; Péter Rajna; György Rásonyi; Joy Desai; Sudhir Kothari; Sita Sattaluri; Bhawna Sharma; Nandan Yardi; Jagarlapudi Murthy; Manmohan Mehndiratta; Kolichana Venkate...; Silvana Francesch...; Guntis Karelis; Guntis Rozentals; Baiba Uskane; Ruta Mameniskiene; Irena Virketiene; Zariah Abdul Aziz; Kheng Seang Lim; Mei-Ling Sharon Tai; Maria Epifania Co...; Katerina Tanya Go...; Anna Czlonkowska; Wieslaw Drozdowski; Waldemar Fryze; Jacek Gawlowicz; Maria Mazurkiewic...; Ewa Motta; Carla Bentes; Luis Cunha; Georgine de Sousa; Jose Manuel Lopes...; Ioana Raluca Mind...; Dezso Nagy; Sanda Maria Nica; Elena Belousova; Vladimir Kalinin; Elena Levitina; Natalya Perunova; Natalya Pizova; Irina Poverennova; Pavel Vlasov; Dragoslav Sokic; Ksenija Bozic; Nebojsa Jovic; Zarko Martinovic; Mirjana Spasic; Seung-Bong Hong; Joong Koo Kang; Sang Ho Kim; Sung Eun Kim; Byung-In Lee; Sang Kun Lee; Yong Won Cho; Francisco Javier ...; Juan Luis Becerra; Antonio Escartín ...; Irene García Morales; Javier López-Trigo; Antonio Valls San...; Juan Carlos Sánch...; Tayard Desudchit; Surachai Likasitw...; Charcrin Nabangchang; Somsak Tiamkao; Nantaporn Tiyapun; Jing-Jane Tsai; Pei-Yuan F. Hsieh; Yu-Lung Tseng; Yu-Li Wu; Sergii Kharchuk; Tetyana Litovchenko; Igor Lutskyy; Iryna Makedonska; Volodymyr Martyniuk; Lidiya Mar'yenko; Volodymyr Smolanka; Petro Voloshyn; Stanislav Yevtush...
• Keywords: Adult; Male; Adolescent; Dose-Response Relationship, Drug; Pyridones; Electroencephalography; Drug Administration Schedule; Intention to Treat Analysis; 3. Good health; Young Adult; 03 medical and health sciences; Epilepsy, Complex Partial; 0302 clinical medicine; Nitriles; Humans; Anticonvulsants; Female; Epilepsies, Partial; Child

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.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.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.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.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.