Full-Length Original Research
Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: A pooled analysis of three phase III studies
Article first published online: 10 MAY 2013
Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
Volume 54, Issue 8, pages 1481–1489, August 2013
How to Cite
Steinhoff, B. J., Ben-Menachem, E., Ryvlin, P., Shorvon, S., Kramer, L., Satlin, A., Squillacote, D., Yang, H., Zhu, J. and Laurenza, A. (2013), Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: A pooled analysis of three phase III studies. Epilepsia, 54: 1481–1489. doi: 10.1111/epi.12212
- Issue published online: 30 JUL 2013
- Article first published online: 10 MAY 2013
- Manuscript Accepted: 2 APR 2013
- Eisai Inc
- Antiepileptic drugs;
- Pooled analysis
Three phase III studies (304 [ClinicalTrials.gov identifier: NCT00699972], 305 [NCT00699582], 306 [NCT00700310]) evaluated perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose.
Patients with partial seizures despite receiving 1–3 antiepileptic drugs were randomized to once-daily placebo, perampanel 8 or 12 mg (studies 304, 305), or placebo, perampanel 2, 4, or 8 mg (study 306). Studies included a 6-week baseline period and double-blind treatment phase (6-week titration; 13-week maintenance). Primary end points were median change in partial seizure frequency (baseline vs. double-blind phase) and percentage of patients achieving ≥50% reduction in seizure frequency (baseline vs. maintenance). Here, these end points, together with secondary, exploratory, and safety end points, were assessed using pooled study data.
The pooled intent-to-treat analysis set (randomized, treated patients with any seizure data) included 1,478 patients. Median changes in partial seizure frequency were greater with perampanel than placebo (perampanel 4 mg, −23.3%; 8 mg, −28.8%; 12 mg, −27.2%; placebo, −12.8%; p < 0.01, each dose vs. placebo), as were 50% responder rates (perampanel 4 mg, 28.5%; 8 mg, 35.3%; 12 mg, 35.0%; placebo, 19.3%; p < 0.05, each dose vs. placebo). In addition, median changes in complex partial plus secondary generalized seizure frequency were also greater with perampanel than placebo (perampanel 4 mg, −31.2%; 8 mg, −35.6%; 12 mg, −28.6%; placebo, −13.9%). Perampanel was generally well tolerated. The most frequent treatment-emergent adverse events (TEAEs) were dizziness, somnolence, and headache. Most TEAEs were mild/moderate; relatively few patients experienced severe TEAEs (placebo, 5.4%; perampanel, 8.9%) or serious TEAEs (placebo, 5.0%; perampanel, 5.5%). There were no deaths and no clinically important mean changes in laboratory values, electrocardiography (ECG) findings, or vital signs.
Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile.