According to a study published in Epilepsia, perampanel was both effective and well tolerated as a therapeutic option for reducing the frequency of tonic-clonic seizures in both Asian and non-Asian patient populations.
The investigators conducting this post hoc analysis sought to compare the efficacy and safety of perampanel vs placebo for improved seizure control in patients with tonic-clonic seizures in both Asian and non-Asian patient populations.
Of the 2346 patients in the intent to treat population, 969 patients aged 12 years or older had uncontrolled focal seizures with or without focal to bilateral tonic-clonic seizures or generalized tonic-clonic seizures; 384 patients were Asian, and 585 were non-Asian. Participants from four phase 3 studies (ClinicalTrials.gov identifiers NCT00699972, NCT00699582, NCT 00700310, and NCT 01618695) with focal and focal to bilateral tonic-clonic seizures were randomly assigned to receive perampanel 2 mg, 4 mg, 8 mg, or 12 mg once daily or placebo. These studies included a 6-week baseline period, a 6-week double-blind titration period, and a 13-week maintenance period.
In one phase 3 study (ClincialTrials.gov identifier NCT01393743), participants with generalized tonic-clonic seizures were randomly assigned to receive perampanel 8 mg or placebo; this study included a 4-week titration period and 13-week maintenance period. In all studies, efficacy outcomes were reported as median percentage change in focal to bilateral tonic-clonic or generalized tonic-clonic seizure frequency per 28 days during the double-blind treatment phase, and a 50% reduction in focal seizures in the maintenance period vs baseline.
In the Asian population, the median percentage change in focal to bilateral tonic-clonic seizure frequency was significantly greater for perampanel 8 mg vs placebo (-30.32% difference; 95% CI, -48.673 to -9.144; P =.0017) and 12 mg vs placebo (-30.06%; 95% CI, -46.238 to -11.071; P =.0008). In the non-Asian population, the median percentage change in focal to bilateral tonic-clonic seizure frequency vs placebo was significantly greater for perampanel 4 mg (-35.07%; 95% CI, -55.460 to -17.172; P =.0001), 8 mg (-37.78%; 95% CI, -52.737 to -23.554; P <.0001), and 12 mg (-34.53%; 95% CI, -52.273 to -19.395; P <.0001).
In both populations, median percentage change in generalized tonic-clonic seizure frequency was significantly greater for perampanel 8 mg vs placebo (Asian, -37.37%; 95% CI, -62.745 to 0.000; P =.0139; non-Asian, -27.04%; 95% CI, -44.844 to -11.527; P =.0006). When tonic-clonic seizure data was pooled, the researchers identified similar patterns of response to perampanel in both populations.
The 50% responder rate for perampanel 4 mg was significantly greater vs placebo only in the non-Asian population (53.7%; P =.0361); however, the 50% responder rate for perampanel 8 mg and 12 mg was significantly greater vs placebo among both Asian and non-Asian populations (P <.0001-.0050). For generalized tonic-clonic seizures, the 50% responder rates were significantly greater than placebo for perampanel 8 mg in both populations (Asian, P =.0209; non-Asian, P =.0329). Overall, the most common treatment-related adverse events were fatigue, irritability, dizziness, somnolence, and headache; serious treatment-emergent adverse events only occurred in 5.1% of patients taking placebo and 4.4% of patients taking any dose of perampanel.
Limitations to the study included differences in specific seizure subtypes, in which efficacy findings were dominated by data for focal to bilateral tonic-clonic seizures. Furthermore, an equal distribution of patients from Asian and non-Asian populations was not achieved.
The investigators concluded that perampanel was effective and well tolerated to improve seizure control in Asian and non-Asian patients experiencing tonic-clonic seizures. Overall, patients receiving perampanel 8 mg and 12 mg were more likely to achieve a 50% reduction in the frequency of seizures, and roughly a third of both populations achieved seizure freedom.
Disclosures: Several researchers declare affiliations with pharmaceutical companies. For a full list of disclosures, please see the reference.
Nishida T, Lee SK, Wu T, Tiamkao S, Dash A. Efficacy and safety of perampanel in generalized and focal to bilateral tonic-clonic seizures: a comparative study of Asian and non-Asian populations [published online March 14, 2019]. Epilepsia. doi: 10.1111/epi.14644