• Determine the maximum tolerated dose by assessing incidence of dose reduction and discontinuation due to adverse event among RWJ-333369-treated patients compared with placebo-treated patients.
  

• Percent reduction in seizure frequency during the maintenance treatment phase, compared with the pretreatment retrospective baseline period.
  

RWJ-333369 is a new chemical compound with anticonvulsant activity. To date, there has been limited experience with the novel compound RWJ-333369 in the clinically relevant patient population, that is, patients with epilepsy. The maximum dose tolerated by patients must be estimated based upon actual experience in the relevant clinical population. The data from this study will be used in guiding the selection of dose ranges in future studies in patients with intractable partial onset seizures.This is a double-blind, placebo-controlled study of the safety, tolerability, and effectiveness of RWJ-333369 as add-on therapy in patients with partial onset seizures (with or without secondary generalization) or primarily generalized tonic-clonic seizures currently treated with at least 1 of the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, or oxcarbazepine. The study is divided into the following phases: a screening and prerandomization phase, double-blind treatment including titration and maintenance phases, and taper and discontinuation or transition to open-label and long-term extension phases. During the double-blind phase, doses of RWJ-333369 will be increased in steps to determine the maximum tolerated dose. The tolerability of the dose in each ascending step will be defined as the proportion of patients who attain that dose without the occurrence of adverse events causing dose reduction or discontinuation from the study. A poorly tolerated dosage that causes adverse events will result in dose reduction or discontinuation of RWJ-33369. Effectiveness will be evaluated based on counts of all partial onset seizures and generalized tonic-clonic seizures occurring during the retrospective 56-day baseline period and the 28-day maintenance treatment period. The study hypothesis is that a dose of RWJ-333369, used in addition to existing epilepsy treatment, in patients with partial onset seizures, will be identified that is tolerated as well as placebo. A dose of RWJ-33369 will be considered well tolerated if the incidence of dose reduction and discontinuation is not substantially greater among RWJ 333369-treated patients than among placebo-treated patients at that same dosage step.

Initial dose RWJ-333369 is 1 capsule (250 milligram (mg)) taken twice daily. Dosage may be changed at weekly intervals. The maximum permitted dose will be 4 capsules (1000 mg), twice daily. Double blind-treatment duration is up to 71 days with the option to continue treatment in an open-label study.