Abstracts

Rationale: The efficacy and safety of pregabalin monotherapy for the treatment of partial onset seizures was demonstrated in a recent randomized, double-blind, conversion-to-monotherapy, historical-controlled trial. This open-label extension evaluated the long-term safety and efficacy of pregabalin monotherapy in patients completing the double-blind trial. Methods: Patients completing the 20-week double-blind phase of the preceding trial transitioned from pregabalin 150 or 600 mg/day to open-label pregabalin 300 mg/day over 7 days. Patients received open-label pregabalin monotherapy for 24 weeks, with dose adjustment over the range 150-600 mg/day (based on investigator judgment). Safety was evaluated by monitoring of adverse events (AEs), laboratory measures and vital signs. Seizure rates were also reported based on daily seizure diaries. Results: A total of 73 patients received ≥1 dose of open-label pregabalin; 58 (79.5%) completed 24 weeks of treatment. The most frequent reasons for discontinuation were insufficient clinical response (5 patients) and AEs (4). Median duration of treatment was 174 days (range 27-200) and the median average daily dose of pregabalin was 473.7 mg/day (range 275-600). Overall, 31 (42.5%) patients had ≥1 treatment-emergent AE (all causalities); the majority were mild or moderate in intensity. The most common treatment-emergent AEs were convulsion (increase in seizure frequency or intensity; 5 patients), headache (4), nausea (4), arthralgia (3) and increased weight (3). In the preceding double-blind trial, the most common AEs were somnolence and dizziness. No new AEs of somnolence were observed during open-label treatment, but 3 patients experienced ongoing somnolence that began during the double-blind trial. 2 patients had treatment-emergent AEs of dizziness and 2 had ongoing dizziness that began during the double-blind trial. 3 patients had a total of 4 serious AEs, 1 of which (convulsion) was considered treatment-related. 2 patients withdrew due to treatment-emergent AEs of convulsion (1 of which was considered treatment-related) and 2 due to AEs of increased weight that began during double-blind treatment (both treatment-related). 3 patients had a total of 4 treatment-emergent AEs leading to dose reduction (nausea, hypertension, dizziness, and headache), all of which were considered treatment-related. Changes in vital signs and laboratory measures were generally minor and not considered clinically significant. 63 (86.3%) patients experienced ≥1 seizure during open-label treatment; the most frequent seizure types were complex partial and simple partial seizures. 10 (13.7%) patients were seizure-free for the duration of open-label treatment, 9 of whom completed the study. Conclusions: In this 24-week, open-label study, pregabalin was generally safe and well tolerated, with a safety profile consistent with previous clinical trials. Almost 80% of patients completed 6 months of open-label pregabalin monotherapy, and 10 were seizure-free for the duration of the study.