A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Vigabatrin Protocol 024 Investigative Cohort.

This study compared the efficacy and tolerability of vigabatrin 3/day as add-on therapy with that of placebo in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day during a 4-week titration segment and maintained it at 3 g/day during the 12-week maintenance segment. By analyses we found a statistically significant lower frequency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo. The median monthly frequency was reduced by three seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared with 17 of those treated with placebo (19%) (p < 0.001). Vigabatrin significantly increased the mean number of seizure-free days per 28 days (2.2 days) compared with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration during therapy was 8.6 +/- 7.7 micrograms/ml. The oral clearance of vigabatrin was determined to be 7.8 L/hr, and the elimination half-life was 8.4 hours. No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vigabatrin treatment. The results of this study indicate that 3 g/day vigabatrin is more effective than placebo as add-on therapy. Vigabatrin was well tolerated, compliance was high with twice-daily administration, and therapy did not result in clinically relevant drug interactions.