A post hoc analysis of the long‐term safety and efficacy of perampanel in Asian patients with epilepsy

This post hoc analysis assessed the long‐term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic‐clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long‐term extension phase of 3 phase‐3 perampanel trials (study 307) or the 10‐week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double‐blind phase‐3 trials and 669 had previously received perampanel 2‐12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment‐emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre‐perampanel baseline for all focal seizures was ?28.1%, and ?51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre‐perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long‐term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase‐3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.     

CYP2A6 genotypes and coumarin-oxidation phenotypes in a Thai population and their relationship to tobacco smoking

Objective  To investigate the association between polymorphisms in the human CYP2A6 gene, CYP2A6 enzyme activity and the influence of cigarette smoking in a Thai population. Methods  Coumarin (5 mg capsule) was administered to 194 healthy Thai subjects. Genetic variation of the CYP2A6 gene was identified using PCR methods. The excreted dose of 7-hydroxycoumarin (as a percentage of the urine concentration) 2 h after administration was calculated as an index of coumarin metabolism. Results  The frequencies of CYP2A6 alleles *1A, *1B, *4C, *7, *8, *9 and *10 were 34.0, 35.3, 9.3, 6.4, 0.5, 12.1 and 2.4%, respectively. Of the 194 subjects tested, the number (percentages) of Thai participants classified as ultra-rapid, extensive, intermediate and poor metabolizers were 8 (4.1%), 159 (82.0%) 22 (11.3%) and five (2.6%), respectively. Conclusion  A relationship between the interindividual differences in coumarin metabolism and genetic polymorphisms of the CYP2A6 gene was observed.