Adjunctive perampanel in partial‐onset seizures: Asia‐Pacific, randomized phase III study. (17th December 2017) - Nishida, T.
Abstract : Objectives: To evaluate the efficacy, safety, and tolerability of perampanel, a selective, non‐competitive, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist, as an adjunctive treatment for patients with refractory partial‐onset seizures (POS) from Asia‐Pacific. Materials & methods: This multicenter, randomized, double‐blind, placebo‐controlled trial (ClinicalTrials.gov identifier: NCT01618695) involved patients aged ≥12 years with refractory POS (receiving 1‐3 antiepileptic drugs). Patients were randomized (1:1:1:1) to receive once‐daily placebo or perampanel 4, 8, or 12 mg over a 6‐week titration and 13‐week maintenance double‐blind period. Enzyme‐inducing antiepileptic drugs were equally stratified between groups. The primary efficacy endpoint was percent change in POS frequency per 28 days (double‐blind phase vs baseline). Other efficacy endpoints included ≥50% responder rate and seizure freedom. Treatment‐emergent adverse events (TEAEs) were also monitored. Results: Of 710 randomized patients, seizure frequency data were available for 704 patients. Median percent changes in POS frequency per 28 days indicated dose‐proportional reductions in seizure frequency: −10.8% with placebo and −17.3% ( P = .2330), −29.0% ( P = .0003), and −38.0% ( P < .0001) with perampanel 4, 8, and 12 mg, respectively. In total, 108 (15.3%) patients discontinued treatment; 44 (6.2%) due to TEAEs. TEAEs occurring in ≥5% of patients, and reported at least twice as frequently with perampanel vs placebo, included dizziness and irritability. Conclusions: Adjunctive perampanel (8 and 12 mg/d) significantly improved seizure control in patients with refractory POS. Safety and tolerability were acceptable at daily doses of perampanel 4‐12 mg.