Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304.

Area of Science:

• Neurology
• Pharmacology

Background:

• Partial-onset seizures are common, and drug resistance necessitates exploring novel therapeutic agents.
• Perampanel is a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist.

Purpose of the Study:

• To evaluate the efficacy and safety of adjunctive perampanel (8 mg or 12 mg once-daily) in patients with drug-resistant partial-onset seizures.
• To assess the impact of perampanel on seizure frequency and responder rates.

Main Methods:

• A multicenter, double-blind, placebo-controlled trial involving patients aged 12 years and older with ongoing seizures despite 1-3 antiepileptic drugs (AEDs).
• Patients were randomized to receive once-daily perampanel (8 mg or 12 mg) or placebo, with a titration period followed by a 13-week maintenance phase.
• Primary efficacy endpoint was the percent change in seizure frequency; a 50% responder rate was also assessed.

Main Results:

• Perampanel 8 mg and 12 mg significantly reduced median seizure frequency compared to placebo (-26.3% and -34.5% vs -21.0%, respectively).
• While 50% responder rates were numerically higher with perampanel (37.6% and 36.1% vs 26.4%), these did not reach statistical significance.
• Most common adverse events included dizziness, somnolence, and irritability; 17.5% of patients discontinued treatment, with 10.3% due to adverse events.

Conclusions:

• Once-daily adjunctive perampanel at 8 mg and 12 mg doses demonstrates efficacy in improving seizure control for patients with uncontrolled partial-onset seizures.
• The studied doses of perampanel were found to be safe, with acceptable tolerability in this patient population.