Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial
Steve Chung, Michael R Sperling, Victor Biton, Gregory Krauss, David Hebert, G David Rudd, Pamela Doty, SP754 Study Group, B Abou-Khalil, M Agostini, I Ali, R Armstrong, R Ayala, J Balmakund, G Barkley, S Benbadis, V Biton, A Blum, M Brown, W Carlini, S Chung, J Cohen, G Connor, J DeCerce, M Evans, T Fakhoury, R Faught, A Fessler, N Foldvary-Schaefer, N Fountain, L Frank, J French, S Gazda, J Gibbs, J Halford, W Hamilton, C Harden, S Helmers, A Husain, S Karner, Y Kaydanova, D King-Stephens, S Kirzinger, J Klapper Jr, P Klein, D Ko, G Krauss, K Krishnamurthy, P Lee-Kwen, R Leroy, D Leszczyszyn, K Liow, J Liporace, P Mazzeo, P McAllister, P McCabe, W McElveen, J Miller, G Montouris, J Moore, G Morris 3rd, W Noland, A Palade, P Parcells, E Passaro, P Penovich, B Phillips, M Privitera, N Rodgers-Neame, J Rogin, W Rosenfeld, R Sachdeo, V Salanova, M Sam, E Sandok, M Sazgar, J Shih, J Sirven, M Sperling, E Spokoyny, W Tatum 4th, T Ting, J Tomasovic, B Vazquez, M Werz, Steve Chung, Michael R Sperling, Victor Biton, Gregory Krauss, David Hebert, G David Rudd, Pamela Doty, SP754 Study Group, B Abou-Khalil, M Agostini, I Ali, R Armstrong, R Ayala, J Balmakund, G Barkley, S Benbadis, V Biton, A Blum, M Brown, W Carlini, S Chung, J Cohen, G Connor, J DeCerce, M Evans, T Fakhoury, R Faught, A Fessler, N Foldvary-Schaefer, N Fountain, L Frank, J French, S Gazda, J Gibbs, J Halford, W Hamilton, C Harden, S Helmers, A Husain, S Karner, Y Kaydanova, D King-Stephens, S Kirzinger, J Klapper Jr, P Klein, D Ko, G Krauss, K Krishnamurthy, P Lee-Kwen, R Leroy, D Leszczyszyn, K Liow, J Liporace, P Mazzeo, P McAllister, P McCabe, W McElveen, J Miller, G Montouris, J Moore, G Morris 3rd, W Noland, A Palade, P Parcells, E Passaro, P Penovich, B Phillips, M Privitera, N Rodgers-Neame, J Rogin, W Rosenfeld, R Sachdeo, V Salanova, M Sam, E Sandok, M Sazgar, J Shih, J Sirven, M Sperling, E Spokoyny, W Tatum 4th, T Ting, J Tomasovic, B Vazquez, M Werz
Abstract
Purpose: To evaluate the efficacy and safety of lacosamide (400 and 600 mg/day) as adjunctive treatment in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs).
Methods: This multicenter, double-blind, placebo-controlled trial randomized patients 1:2:1 to placebo, lacosamide 400 mg, or lacosamide 600 mg/day. After an 8-week baseline period, patients began treatment with placebo or lacosamide 100 mg/day, were force-titrated weekly (100 mg/day increments) to the target dose, and entered a 12-week maintenance period.
Results: A total of 405 patients were randomized and received trial medication. Most (82.1%) were taking two to three concomitant AEDs. Median percent reductions in seizure frequency per 28 days from baseline to maintenance (intention-to-treat, ITT) were 37.3% for lacosamide 400 mg/day (p = 0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for placebo, with responder rates of 38.3% and 41.2%, respectively, compared to placebo (18.3%, p < 0.001; ITT). Patients randomized to lacosamide showed large reductions in secondarily generalized tonic-clonic seizures, with median percent reductions in seizure frequency of 59.4% for lacosamide 400 mg/day and 93.0% for lacosamide 600 mg/day compared to 14.3% for placebo, and responder rates of 56.0% and 70.2% compared to placebo (33.3%). Dose-related adverse events included dizziness, nausea, and vomiting.
Discussion: Adjunctive treatment with lacosamide 400 and 600 mg/day reduced seizure frequency for patients with uncontrolled partial-onset seizures. Lacosamide 400 mg/day provided a good balance of efficacy and tolerability; lacosamide 600 mg/day may provide additional benefit for some patients as suggested by secondary efficacy analyses, including response in patients with secondarily generalized tonic-clonic seizures.
Source: PubMed