Adjunctive Treatment Improves Control of Partial Seizures

Concomitant AED and perampanel treatment was well tolerated by patients with secondarily generalized seizures.

VANCOUVER, British Columbia—Perampanel is a noncompetitive AMPA receptor antagonist that is used as an adjunct for the treatment of partial seizures.  In phase 3 trials involving patients with partial seizures with and without secondarily generalized seizures (SGSs), perampanel was found to be well tolerated and to have a positive effect on the frequency of seizures when used concomitantly with up to 3 antiepileptic drugs (AEDs) for up to 2 years.

Emilio Perucca, MD, president of the International League Against Epilepsy (ILAE) and director of the Clinical Trial Centre at the C. Mondino National Neurological Institute in Pavia, Italy, and an international team of investigators conducted a study to further evaluate seizure outcomes in patients treated with perapanel for 3 to 4 years.

The study results were presented at the 68th annual meeting of the American Academy of Neurology.

A total of 1218 patients from the aforementioned double-blind, phase 3 studies were randomly assigned to receive either placebo or perampanel 2, 4, 8, or 12 mg daily.  Participants were then eligible to enroll in the open-label extension period, which consisted of a 16-week, blinded conversion period and a long-term, open-label maintenance phase.  Patients were continued on their established dosage of perampanel; however, those on placebo or receiving perampanel <12 mg/d were uptitrated to perampanel 12 mg/d or to the maximum tolerated dose.

A total of 73.5% of participants in the Safety Analysis Set (n=894) received perampanel for at least 1 year, 56% (n=681) received perampanel for at least 2 years, 35.9% (n=436) received treatment for at least 3 years, and 6.4% (n=78) received treatment for at least 4 years. Most of the participants were taking 2 to 3 concomitant AEDs at baseline.

Analysis revealed improved long-term seizure outcomes in the overall population, with seizure improvement sustained for 4 years. For those participants who had SGS at baseline, median percentage reductions in seizures during the last year of perampanel treatment  for participants who took the medication for at least 1, 2, 3, or 4 years were 46.7%, 57.1%, 61.8%, and 68.9% percent, respectively.  Corresponding response rates were 47.4%, 54.4%, 59.5%, and 64.3%, respectively.

It should be noted that participants who did not have SGS at baseline but who experienced SGS while undergoing treatment with perampanel were excluded from the analysis.

There was at least 1 treatment-related adverse event reported by 92.9% of participants during the entire treatment period; most were considered mild or moderate.  At least 10% of participants reported dizziness, somnolence, headache, fatigue, weight gain, irritability, and nasopharyngitis.  Serious adverse events were experienced by 23.7% of participants, with the most common related to epilepsy (eg, convulsion, status epilepticus, epilepsy, grand mal convulsion, etc).  A total of 19% of participants discontinued treatment during the 4-year period due to adverse events.

The researchers concluded that “long-term adjunctive treatment with perampanel … was well tolerated and associated with sustained markedly improved seizure control, particularly in subjects with SGS at baseline.”  These data contribute to the established findings on the use of perampanel as adjunctive treatment for partial seizures with and without SGS.

Click here for more coverage from the 68th Annual Meeting of the American Academy of Neurology, April 15-21, 2016, in Vancouver, British Columbia, Canada.


Perucca EM, Krauss GL, Kwan P, et al. Marked reduction in secondarily generalized seizures (SGS) in patients treated with perampanel for 3 and 4 years.   Presented at: The 68th Annual Meeting of the American Academy of Neurology; April 15-21, 2016; Vancouver, British Columbia. Poster P5.405.