Portal de Periódicos da CAPES

Adjunctive perampanel for refractory partial-onset seizures

2012; Lippincott Williams & Wilkins; Volume: 79; Issue: 6 Linguagem: Inglês

10.1212/wnl.0b013e3182635735

1526-632X

Jacqueline A. French, Gregory L. Krauss, Victor Biton, David Squillacote, Haichen Yang, Antonio Laurenza, Dinesh Kumar, Michael A. Rogawski, Verónica Campanille, Jorge Floridia, Rita Ilari, D. Consalvo, Alfredo Thomson, Ignacio Sfaello, Juan Pociecha, Flavia Nieto, Alfredo José Firstenfeld, Daniel Raúl Zuin, Jacobo C. Mesri, Walter Silva, Pedro Nofal, Diana Cristalli, Jean‐François Clément, Paul M. Hwang, Richard S. McLachlan, Neelan Pillay, J. Lasso, B Peralta, Marcelo Leiva Hernandez, E Tenhamm, Noe Barroso, Albino Contreras Milian, Sarug Reyes Morales, Ildefonso Rodríguez‐Leyva, Sanjay Jain, Angus A. Wilfong, Arun Kalra, Ben Renfroe, David Moore, J. Robert Flamini, Jack A. Klapper, Jerzy P. Szaflarski, Jean Teasley, Jonathan J. Halford, José Alexandre Ferreira, Hewitt C. Goodpasture, Michael R. Sperling, Pavel Klein, Ricardo Ayala, Richard Brower, Robert Leroy, Ronald L. Davis, Roy D. Elterman, Thomas Enlow, Verónica Sosa, Vinay Puri, J. Philip Miller, Bassel F. Shneker, Ramon Edmundo D. Bautista, Steve Chung, David Lesch, David F. Steiner, Randall Webb, Robert Armstrong, Victor Biton, Gregory L. Krauss, Wendy G. Mitchell, R. Edward Hogan, Robert C. Knowlton, James W. Wheless, R. Aung-Din, Imran Ali, Lawrence W. Brown, Michael Gruenthal, Pongkiat Kankirawatana, Michael Charlet, Joan A. Conry, Meriem Bensalem Owen, Mark S. Yerby, Craig Herrman, Albert Fessler, Pradeep N. Modur, Fernando Pellon de Miranda, David King‐Stephens,

Ion channel regulation and function

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.