WASHINGTON – The antiepileptic drug perampanel cut the frequency of primary generalized tonic-clonic seizures by 50% versus placebo in patients who were already taking a number of other anti-seizure medications in a phase III randomized trial.
Perampanel (Fycompa), a glutamate receptor blocker, was also associated with significantly higher rates of patients being seizure free or having at least a 50% response, compared with placebo, Dr. Jacqueline French reported at the annual meeting of the American Academy of Neurology.
The study randomized 164 patients to either placebo or up to 8 mg daily of perampanel. It was conducted at 78 sites in 16 countries. There was a run-in period of 4-8 weeks, followed by a month of titration, 13 weeks of maintenance therapy, and a 3-year extension phase. Of 164 patients randomized, 162 completed the entire study, said Dr. French, codirector of epilepsy research and epilepsy clinical trials at the NYU Comprehensive Epilepsy Center, New York. She is also chief scientific officer of the Epilepsy Foundation of America.
The patients were all at least 12 years old and taking up to three other antiepileptic drugs without complete seizure control. During the 8-week pre-randomization period, they had to experience at least three primary generalized tonic-clonic (PGTC) seizures.
At the end of follow-up, add-on perampanel significantly outperformed placebo in the primary measure of change in PGTC seizure frequency (median 76% vs. 38%). It also conferred a significant advantage in the percentage of patients with at least a 50% reduction in seizure frequency (64% vs. 39%). Significantly more patients in the perampanel group became seizure-free (31% vs. 12%).
The safety dataset comprised 163 patients. Most patients taking perampanel (83%) experienced some kind of drug-related adverse event. The most common were dizziness (32% vs. 6% placebo), fatigue (15% vs. 6%), and headache (12% vs. 10%). Six serious adverse events occurred in the active group and seven in the placebo group. There were two deaths, one in each group: an accidental drowning in the perampanel group and a case of sudden unexplained death in epilepsy (SUDEP) in the placebo group.
Perampanel is approved as an adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy aged 12 years and older.
Eisai Inc. sponsored the study. Dr. French has received personal compensation and research support from Eisai, as well as numerous other pharmaceutical companies.
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