DEZINAMIDE FOR PARTIAL SEIZURES - RESULTS OF AN N-OF-1 DESIGN TRIAL

Background. Dezinamide (DZM, ADD 94057) is a potential antiepileptic d rug that binds to the voltage-sensitive sodium channel and showed prel iminary evidence of efficacy and safety in an open-label study. Method s. Our double-blind, placebo-controlled trial at two sites used an n-o f-1 (single-patient) design. All 15 patients had medically intractable partial-onset seizures and were comedicated with phenytoin (PHT) only . Treatment was for six and week periods (three active paired with thr ee placebo in random sequence). Assuming nonlinear kinetics, we used a n initial pharmacokinetic profile to estimate dosages for reaching tar get plasma concentrations of DZM. Results. Statistically significant s eizure reduction was found by both a randomization test (p = 0.0025) a nd a signed rank test (p = 0.048). Median seizure frequency decreased 37.9%, and 40% of patients had >50% seizure reduction, both compared w ith placebo. Pharmacokinetic predictions were not accurate; mean plasm a concentrations fell well below target values. Plasma PHT concentrati ons increased (mean = 17.1%) during DZM treatment. The most common adv erse experiences were fatigue, light-headedness, and abnormal gait; fi ve patients required DZM dosage reductions. Conclusions. DZM showed mi nimal clinical toxicity and significant efficacy despite lower plasma concentrations than predicted by pharmacokinetics. This trial establis hes the suitability of the n-of-1 design to investigational antiepilep tie drug trials.