Perampanel Well-Tolerated for Long-Term Epilepsy Treatment

Perampanel was safe and effective after long-term use in patients with partial-onset seizures, according to a recent study.

Researchers from Japan included 30 patients in a test of adjunctive perampanel ≤12 mg/day in order to evaluate the long-term tolerability, safety, and efficacy of the drug. Perampanel is a selective, non-competitive, orally active agent antagonist of the AMPA receptor which can interrupt epileptic activity. In Japan, it is approved for use in patients aged 12 years or older with partial onset seizures or with or without secondarily generalized seizures, plus primary generalized tonic-clonic seizures. It is also approved in the United States for monotherapy in partial onset seizure patients over 12.

The 10-week treatment period was part of a phase 2, multicenter, open-label trial with increasing doses. The first part of the study was called “Study 231” and the subsequent extension of the study was called “Study 233.” Study 231 was conducted in 2009 and Study 233 was conducted from 2009 to 2016, both at 9 different sites in Japan.

There were 21 patients who received perampanel ≥8 mg/day and 10 patients who received a maximum tolerated dose of 12 mg/day as part of Study 231, the researchers reported. The average drop in seizure frequency reached 35% over 28 days, they also said. There were 4 patients who achieved seizure freedom, the study authors determined.

Study 233 included 21 patients who had a mean duration of exposure of 195 weeks; however, 9 patients received perampanel for up to 208 weeks. For 3 of the Study 233 patients, their seizure control lasted 316 weeks. Two patients reached seizure freedom, the researchers observed.

Treatment-emergent adverse effects (TEAEs) were noted by the investigators at each patient visit and reported. It was also the responsibility of the investigator to judge the causal relationship for all TEAEs as unrelated to related to perampanel.

TEAEs were reported in 27 patients in Study 231 and every patient in Study 233 reported TEAEs. The majority of these were mild or moderate in their severity. The most common side effect was dizziness, as well as some somnolence.

Despite the small numbers in this study, the researchers wrote, the efficacy data about the maximum tolerated dose “suggested that the higher perampanel doses were associated with greater efficacy.” This has been shown in previous studies of perampanel in phase 3 trials, they said.

“Overall, Studies 231 and 233 demonstrate the long-term tolerability, safety, and efficacy of adjunctive perampanel when administered doses of up to 12 mg/day for ≤ 316 weeks (>6 years),” the study authors concluded. “These results support the use of perampanel for the adjunctive treatment of refractory partial onset seizures, with or without secondarily generalized seizures, in Japanese patients aged between 20 and 65 years.”

The paper, “Long-term tolerability, safety and efficacy of adjunctive perampanel in the open-label, dose-ascending Study 231 and extension Study 233 in Japanese patients with epilepsy” was published in Seizure.