Abstract
ObjectiveOur study assessed perampanel monotherapy in patients (aged ≥12 years) with focal‐onset seizures (FOS) with or without focal to bilateral tonic‐clonic seizures (FBTCS) in Japan and South Korea.MethodsStudy 342 (NCT03201900; FREEDOM) is a single‐arm, open‐label, Phase III study. Patients initially received perampanel in a 32‐week 4‐mg/d Treatment Phase (6‐week Titration; 26‐week Maintenance Periods). If they experienced a seizure during the 4‐mg/d Maintenance Period, they could be up‐titrated to 8 mg/d across an additional 30‐week Treatment Phase (4‐week Titration; 26‐week Maintenance Periods). Primary endpoint was the seizure‐freedom rate during the Maintenance Period (4 mg/d and last evaluated dose [4 or 8 mg/d]). Secondary endpoints included time to first seizure onset and to withdrawal during Maintenance. Treatment‐emergent adverse events (TEAEs) were monitored.ResultsAt data cutoff (February 28, 2019), 89 patients with FOS (84 [94.4%] with newly diagnosed epilepsy and 5 [5.6%] with recurrence of epilepsy after a period of remission) had received ≥1 perampanel dose; 16 patients discontinued during the 4‐mg/d Titration Period, meaning 73 patients entered the 4‐mg/d Maintenance Period and were included in the primary analysis set for efficacy. Seizure‐freedom rate in the 26‐week Maintenance Period was 46/73 (63.0%; 95% confidence interval [CI]: 50.9‐74.0) at 4 mg/d and 54/73 (74.0%; 95% CI: 62.4‐83.5) at 4 or 8 mg/d. Cumulative probability of seizure‐onset and withdrawal rates during Maintenance was 30.8% (95% CI: 21.5‐43.0) and 23.7% (95% CI: 15.4‐35.3) at 4 mg/d, and 18.2% (95% CI: 11.0‐29.3) and 23.3% (95% CI: 15.2‐34.8) at 4 or 8 mg/d. Perampanel was generally well tolerated, and the most common TEAE was dizziness.SignificancePerampanel monotherapy (4 to 8 mg/d) was efficacious and consistent with the known safety profile up to 26 weeks in patients (≥12 years) with primarily newly diagnosed FOS with or without FBTCS.
Highlights
It has been shown that some patients with newly diagnosed epilepsy can achieve seizure freedom following treatment with antiepileptic drug (AED) monotherapy while other patients are not able to achieve seizure freedom to the same extent.[1,2,3,4,5,6] The likelihood of achieving seizure freedom reduces with the number of AEDs, with patients who have received2 successive AEDs having a significantly lower seizure-freedom rate than patients treated with 1 AED.[6]
Perampanel 4-mg/d monotherapy, the lowest dosage administered in this study, was associated with efficacy for up to 26 weeks in primarily newly diagnosed patients with focal-onset seizures (FOS) from Japan and South Korea
For the primary endpoint and based on other studies of AEDs as monotherapy,[15,16,17,18,19] prespecified efficacy criteria were fulfilled as the lower 95% confidence interval (CI) of the seizure-freedom rate during the 26-week Maintenance Period was above the threshold of 40%
Summary
It has been shown that some patients with newly diagnosed epilepsy can achieve seizure freedom following treatment with antiepileptic drug (AED) monotherapy while other patients are not able to achieve seizure freedom to the same extent.[1,2,3,4,5,6] The likelihood of achieving seizure freedom reduces with the number of AEDs, with patients who have received. 2 successive AEDs having a significantly lower seizure-freedom rate than patients treated with 1 AED.[6] Guidelines provided by the International League Against Epilepsy (ILAE). Perampanel is an orally active, noncompetitive, selective α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist.[8] In the United States, perampanel is approved as adjunctive therapy and monotherapy for the treatment of focal-onset seizures (FOS; previously known as partial-onset seizures) with or without focal to bilateral tonic-clonic seizures (FBTCS; previously known as secondarily generalized seizures) in patients 4 years of age and above, and as adjunctive treatment of generalized-onset tonic-clonic seizures (previously known as primary generalized tonic-clonic seizures) in patients 12 years of age and above.[9] For FOS, the recommended maintenance dose range of perampanel is 8 mg to 12 mg once daily. Some may respond to a dose of 4 mg/d; the efficacy of this dose has not been fully clarified
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