Perampanel for adjunctive treatment of partial- onset seizures: A pooled dose- response analysis of phase III studies

ObjectiveTo better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. MethodsSeizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8mg, and who received an actual (last) dose of 12mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p=0.042), analyses excluded patients from the Latin America region (n=162/1,480; 10.9% of the treated cohort). ResultsOf 372 patients randomized to 8mg in the phase III studies, 273 completed the Maintenance Period at 8mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12mg during the extension blinded Conversion Period (n=217), median percent change in seizure frequency per 28days improved from -32.4% (8mg, phase III Maintenance Period) to -44.2% (12mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8mg and had an actual (last) dose of 12mg during weeks 1-13 of the extension Maintenance Period (n=181), median percent change in seizure frequency per 28days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12mg and continued on that dose during the extension. SignificanceIncreasing perampanel dose from 8 to 12mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.