Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study

Area of Science:

• Neurology
• Pharmacology
• Epilepsy Research

Background:

• Refractory partial-onset seizures (POS) pose a significant treatment challenge.
• Selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists represent a therapeutic target.
• Perampanel is an investigational AMPA receptor antagonist.

Purpose of the Study:

• To evaluate the efficacy, safety, and tolerability of perampanel as adjunctive therapy for refractory POS in the Asia-Pacific region.
• To determine the dose-response relationship of perampanel in this patient population.

Main Methods:

• A multicenter, randomized, double-blind, placebo-controlled trial (NCT01618695) was conducted.
• Patients aged ≥12 years with refractory POS received placebo or perampanel (4, 8, or 12 mg) once daily for a 19-week double-blind period.
• The primary efficacy endpoint was the percent change in POS frequency per 28 days.

Main Results:

• Perampanel demonstrated dose-proportional reductions in seizure frequency: -17.3% (4 mg), -29.0% (8 mg, P=.0003), and -38.0% (12 mg, P<.0001) compared to placebo (-10.8%).
• The ≥50% responder rate and seizure freedom were also improved with perampanel.
• Treatment-emergent adverse events (TEAEs) included dizziness and irritability, with 6.2% of patients discontinuing due to TEAEs.

Conclusions:

• Adjunctive perampanel at 8 and 12 mg/day significantly improved seizure control in patients with refractory POS.
• Perampanel was generally safe and well-tolerated at daily doses of 4-12 mg in this population.