HONOLULU – Daily adjunctive therapy with the investigational oral drug perampanel significantly reduced the frequency of seizures by 5%-14%, compared with placebo in a multinational phase III clinical trial in 388 patients with hard-to-control epilepsy. Even better results were seen in the approximately half of patients who were in North America in a post hoc analysis.

The frequency of seizures declined by 5% over a 28-day period in patients who were randomized to 8 mg/day of perampanel and by 14% in patients who got 12 mg of perampanel, compared with patients on placebo in an intent-to-treat analysis of all treated patients, Dr. Jacqueline A. French and her associates reported at the annual meeting of the American Academy of Neurology.

Dr. Jacqueline A. French

Patients in the study had uncontrolled epilepsy despite being on one to three other antiseizure drugs, and they continued their usual medications during the trial.

The placebo group saw a 21% decline in the seizure rate, compared with a 26% decline in the 8-mg perampanel group and a 35% decline in the 12-mg group, said Dr. French, professor of neurology at New York University and director of the clinical trials consortium at the university’s comprehensive epilepsy center.

Speaking at a press conference, she also gave results for a separate measure of success preferred by European regulators: the percentage of patients with at least a 50% decline in seizures on the drug. The 50%-responder rate was relatively high in the placebo group at 26% and was 38% in the 8-mg group and 36% in the 12-mg group. These differences were not statistically different among groups.

There was a significant difference in the 50%-responder rates, however, looking at only patients with complex partial seizures and secondarily generalized seizures and ignoring patients with simple partial seizures or seizures that tend to be less disabling, she added. Among these more-severe patients, seizure rates were at least halved in 18% on placebo and by 33% in each of the perampanel arms.

Treatment-related adverse effects were the typical ones expected from antiepileptic drugs, mainly dizziness, drowsiness, irritability, headache, falls, and ataxia. There was a clear dose-response relationship to side effects. "This stuff doesn’t scare us as clinicians," Dr. French said. "In epilepsy, we know how to handle that."

In the 8-mg group, 7% stopped the drug because of side effects, compared with 6% on placebo, which was not significantly different. In the 12-mg group, 17% stopped the drug because of adverse events.

A surprising finding in the double-blind study came from post hoc analyses showing that the results varied significantly depending on the location of the patients, Dr. French said.

About half of patients enrolled in the trial were from the United States and Canada. Seizure frequency rates in those patients declined by only 10% in the placebo group and by 27% with 8-mg perampanel and 39% in the 12-mg group. The differences between the drug groups and placebo were highly significant.

04/13/11  

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FROM THE ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY

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Vitals

Major Finding: Daily adjunctive therapy with the investigational oral drug perampanel reduced the frequency of seizures by 5% using an 8-mg dose and by 14% using a 12-mg dose, compared with placebo, in patients with uncontrolled epilepsy already taking one to three antiepileptic drugs.

Data Source: A multinational, randomized, double-blind, placebo-controlled trial in 388 patients.

Disclosures: Eisai Inc., which is developing perampanel, funded the studies. Dr. French has received research support from Eisai and many other companies manufacturing antiepileptic drugs. Some of her associates in the study also disclosed relationships with Eisai and other companies making antiepileptic drugs.

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