Abstracts

RATIONALE: To evaluate two regimens (BID vs TID) of tiagabine (TGB) given as add-on treatment to patients with partial seizures; to evaluate its long-term safety.
METHODS: This was a multicentre, multinational (Sp, UK), open label study comprised of a randomized, parallel-group (BID vs TID), 12-week fixed-schedule phase, followed by a flexible continuation phase for a further 12 weeks at least. TGB dosage was to be titrated up to 40mg/day. During continuation, dose level and frequency could be adjusted within 30-70mg/day.
RESULTS: A total of 247 patients aged 32.8 years with partial epilepsy were randomized of whom 243 were analysed (123 vs 120 in BID vs TID groups respectively, ITT population). Mean duration of epilepsy was 20.5 (+11.8) years, with 6.5 antiepileptic drugs taken on average since epilepsy onset. Doses of TGB were quite similar between groups with patients receiving a mean daily dose of 35.2mg during the flexible continuation. There was no significant difference in the proportion of patients in each group completing the 12-week fixed-schedule period (primary endpoint) though less BID patients completed the fixed period (61.8%) compared to TID(72.5%) (odds ratio, 0.562; 95% CI = 0.309, 1.008; p=0.0532). Over the all study duration, a proportion of 30.9% (vs 25.0%) patients discontinued because of AEs, and 12.2% (vs 10.8%) because of lack of efficacy in the BID group compared to TID. Non induced patients were less likely to complete the study in the BID than in the TID group which may reflect the lesser tolerability of high doses when given undivided (non induced patients were receiving at week 12 an average daily dose of 32.4mg, ie a relatively high dose, compared to 34.5mg in induced patients. Responders (i.e. patients who achieved a decrease in seizure rate of at least 50% from baseline during the last 8 weeks of the continuation period) rates were 27.6% in the BID group compared to 25.8% for TID. Eleven (8.9%) patients in the BID group were seizure free compared to 6 (5%) patients in the TID group during the last 8 weeks of continuation. Similar number of patients reported AEs in both groups with more AEs occurring during the fixed period (81% during the fixed period; 28% during the flexible continuation). Most AEs were mild and CNS related with dizziness being the most frequently reported (27% in the fixed period; 3% during continuation).
CONCLUSIONS: TGB was effective and well tolerated as add-on treatment of partial seizures whether given BID or TID. It is expected that tolerability could be further improved when allowing for a slower titration and /or lower doses in individual patients.
Support: Sanofi-Synthelabo.