Efficacy and safety of perampanel in generalized and focal to bilateral tonic-clonic seizures: A comparative study of Asian and non-Asian populations.

Abstract

Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures and generalized tonic-clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non-Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12 years old) with focal + FBTC seizures received perampanel 2, 4, 8, or 12 mg or placebo; patients with GTC seizures received perampanel 8 mg or placebo (titration: 4-6 weeks; maintenance: 13 weeks). Efficacy endpoints included median percentage change in FBTC or GTC seizure frequency per 28 days and 50% responder rate relative to baseline. Median percentage change in FBTC seizure frequency was significantly greater for perampanel 8 and 12 mg than placebo in the Asian population (median difference from placebo: -30.32%, P = 0.0017; -30.06%, P = 0.0008, respectively) and perampanel 4, 8, and 12 mg in the non-Asian population (-35.07%, P = 0.0001; -37.78%, P < 0.0001; -34.53%, P < 0.0001, respectively). In both populations, median percentage change in GTC seizure frequency was significantly greater for perampanel 8 mg than placebo (median difference from placebo: Asian, -37.37%, P = 0.0139; non-Asian, -27.04%, P = 0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12 mg for FBTC seizures (Asian: 58.0%, P = 0.0017 and 58.6%, P = 0.0013, respectively; non-Asian: 59.3%, P < 0.0001 and 54.3%, P = 0.0050, respectively) and perampanel 8 mg for GTC seizures (Asian: 57.6%, P = 0.0209; non-Asian: 68.8%, P = 0.0329). Pooled FBTC/GTC seizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment-related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option for FBTC/GTC seizures in Asian populations.

• Authors: Takuji Nishida, Sang Kun Lee, Tony Wu, Somsak Tiamkao, Amitabh Dash
• Journal: Epilepsia (Epilepsia) Vol. 60 Suppl 1 Pg. 47-59 (03 2019) ISSN: 1528-1167 [Electronic] United States
• PMID: 30869168 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.

Chemical References

• Anticonvulsants
• Nitriles
• Pyridones
• perampanel

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anticonvulsants (adverse effects, therapeutic use)
• Asian People
• Child
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Epilepsy, Generalized (drug therapy)
• Epilepsy, Partial, Motor (drug therapy)
• Epilepsy, Tonic-Clonic (drug therapy)
• Female
• Humans
• Male
• Middle Aged
• Nitriles
• Pyridones (adverse effects, therapeutic use)
• Seizures (drug therapy)
• Treatment Outcome
• Young Adult