Tolerability and safety of perampanel: two randomized dose-escalation studies

Area of Science:

• Neurology
• Pharmacology
• Clinical Trials

Background:

• Epilepsy affects millions globally, with many experiencing refractory partial-onset seizures.
• Novel therapeutic agents are crucial for managing difficult-to-treat epilepsy.
• Perampanel, a selective, non-competitive AMPA antagonist, offers a new mechanism of action.

Purpose of the Study:

• To assess the tolerability and safety of escalating oral perampanel doses.
• To evaluate perampanel as adjunctive therapy for refractory partial-onset seizures in adults.
• To establish optimal dosing for future large-scale clinical trials.

Main Methods:

• Two randomized, double-blind, dose-escalation studies (206 and 208) were conducted.
• Adults (18-70 years) with uncontrolled partial-onset seizures were enrolled.
• Patients received placebo or perampanel (up to 4 mg/day or 12 mg/day) for 12-16 weeks.

Main Results:

• Perampanel up to 4 mg/day was well tolerated in Study 206 (82.4% tolerability).
• In Study 208, most patients tolerated perampanel doses of ≥ 6 mg once-daily.
• Central nervous system (CNS) related adverse events were most common, generally mild/moderate.

Conclusions:

• Perampanel demonstrated good tolerability at doses ranging from 4-12 mg/day.
• Preliminary evidence of efficacy was observed in patients with refractory partial-onset seizures.
• The studies identified key doses for further investigation in larger clinical trials.