Slow release versus immediate release oxcarbazepine in difficult-to-treat focal epilepsy. A multicenter, randomized, open, controlled, parallel group phase III study

The aim of the study was an assessment of the tolerability and efficacy of slow release oxcarbazepine (OXC-MR) versus immediate release OXC (OXC-IR) after forced titration in patients with focal epileptic seizures with and without secondary generalization who had previously not become seizure-free under OXC-IR with or without concomitant antiepileptic drugs. The primary study variable was to assess the maximum tolerated dosage with OXC-MR and OXC-IR. This was designed as a multicenter, randomized, open, controlled, parallel group phase III study. After randomization patients received OXC-MR or OXC-IR for a study period of 26 days. The initial dosage of 900 mg, 1,200 mg or 1,500 mg OXC was increased every 5 days by 300 mg up to a maximum daily dosage of 2,700 mg. In cases of intolerable adverse events dosage could be reduced by 150 mg 2 days after an increase. Adverse events and executive abilities were assessed with the questionnaire "Adverse Event Profile plus" and with the EpitrackA (R) test protocol. Serum concentrations of OXC and its active metabolite were measured in a part of the patient group. The 71 patients (54% male, age: 19-70 years) enrolled in the study were randomized. The maximum mean daily OXC dosage at the end of the study period was 1,950 mg with OXC-MR and thus statistically significantly higher than in OXC-IR group (1,650 mg, p = 0.022). The number of causally related adverse events was lower in the OXC-MR group (n = 104 versus n = 138 with OXC-IR) and CNS-related adverse events such as dizziness, tremor, somnolence and headache occurred significantly less often with OXC-MR (OXC-MR 65.7%, OXC-IR 88.9%, p = 0.01). Fluctuations of serum concentrations of the active metabolite were less pronounced under the OXC-MR regimen. Due to better tolerability OXC-MR allowed higher maintenance dosages to be reached than OXC-IR. In spite of a higher mean daily dosage adverse events and especially CNS-related adverse events occurred less often than with OXC-IR.