Abstracts

To evaluate the efficacy and tolerability of levetiracetam (LEV) add-on therapy in patients with refractory idiopathic generalised epilepsy (IGE) experiencing myoclonic seizures (MCS) or primary generalised tonic-clonic seizures (PGTCS)., 2 multicentre, placebo (PBO)-controlled, double-blind studies were conducted in IGE patients with MCS (Study N166) or PGTCS (Study N01057). N166 recruited patients, age 12-65 years, experiencing [ge]8 days with [ge]1 MCS during 8 weeks baseline, and receiving 1 standard antiepileptic drug (AED). N01057 recruited patients, age 4-65 years, experiencing [ge]3 PGTCS during 8 weeks baseline, and receiving 1-2 AEDs. LEV was uptitrated over 4 weeks to a target dose of 3000 mg/day (60 mg/kg/day for paediatric patients), and evaluated over 12 (N166) or 20 (N01057) weeks. Efficacy was assessed over the entire treatment period [titration+evaluation]), as responder rate ([ge]50% reduction in seizure days/week [MCS] or seizures/week [PGTCS]), and as seizure freedom rate defined as percentage of seizure-free study completers in the intention-to-treat population over the evaluation period. Tolerability was assessed by evaluating adverse events (AEs)., N166 randomised 122 patients (Juvenile Myoclonic Epilepsy [JME] n=113, Juvenile Absence Epilepsy [JAE] n=9); 60 LEV and 60 PBO patients provided evaluable data. N01057 randomised 164 patients (JME n=54, Epilepsy with Grand Mal Seizures on Awakening n=49, JAE n=19, Childhood Absence Epilepsy n=7, other IGE n=28, unknown syndromes n=7; 79 LEV and 84 PBO patients provided evaluable data.
In N166, responder rates (LEV [italic]vs[/italic] PBO) were 58.3% [italic]vs[/italic] 23.3% (p[lt]0.001) for MCS and 56.7% [italic]vs[/italic] 21.7% (p[lt]0.001) for all seizures; seizure freedom rates were 16.7% [italic]vs[/italic] 3.3% (p=0.029) for MCS and 13.3% [italic]vs[/italic] 0% (p=0.006) for all seizures.
In N01057, responder rates (LEV [italic]vs[/italic] PBO) were 72.2% [italic]vs[/italic] 45.2% (p[lt]=0.001) for PGTCS, and 59.5% [italic]vs[/italic] 29.8% for all seizure types (p[lt]0.001); seizure freedom rates were 24.1% [italic]vs[/italic] 7.1% (p=0.004) for PGTCS and 15.2% [italic]vs[/italic] 6.0% (p=0.072) for all seizures.
In N166, 75.0% LEV [italic]vs[/italic] 66.7% PBO patients reported [ge]1 AE during treatment period; 2 LEV and 1 PBO patient withdrew due to AEs. In N01057, 72.2% LEV [italic]vs[/italic] 67.9% PBO patients reported [ge]1 AE during treatment period; 1 LEV and 4 PBO patients withdrew due to AEs., These studies provide further evidence that LEV is effective and well tolerated in patients with refractory IGE, significantly reducing the frequency of both MCS and PGTCS and substantially increasing the seizure freedom rates in patients with each of these seizure types., (Supported by Funds from UCB.)