Three multicentre, randomized, double-blind, placebo-controlled studies in a total of 1239 adult patients have been conducted to assess the efficacy of retigabine as adjunctive therapy of partial onset seizures, with or without secondary generalisation. All patients enrolled were to have had seizures that were not adequately controlled with 1 to 3 concomitant antiepileptic drugs, and more than 75% of all patients were taking 2 concurrent antiepileptic drugs. Across all studies, patients had a mean duration of epilepsy of 22 years and a median baseline seizure frequency ranging from 8 to 12 per 28 days. Patients were randomized to placebo or retigabine at 600, 900 or 1,200 mg/day (see Table 1). During an 8-week baseline period, patients had to experience 4 partial onset seizures per 28 days. Patients could not be seizure-free for 21 days. The duration of the maintenance phase was 8 or 12 weeks.

The primary efficacy endpoints were:

- percentage change in the 28-day total partial seizure frequency from baseline to the double-blind phase (titration and maintenance phases combined) in all three studies

- responder rate (defined as the percentage of patients with a 50% reduction in 28-day total partial seizure frequency) from baseline to the maintenance phase (Studies 301 and 302 only).

Retigabine was effective in adjunctive treatment of adults with partial onset seizures in three clinical studies (Table 1). Retigabine was statistically significantly superior to placebo at 600 mg/day (one study), 900 mg/day (two studies) and 1,200 mg/day (two studies).

The studies were not designed to eva luate specific combinations of antiepileptic drugs. Consequently, the efficacy and safety of retigabine when taken concomitantly with antiepileptic drugs that were less commonly used as background treatment in the clinical studies, including levetiracetam, has not been definitely shown.

Table 1. Summary of percentage changes in 28-day total partial seizure frequency and responder rates

Study

(n=population in double-blind phase; n=population in maintenance phase)
 Placebo
 Retigabine
 
600

mg/day
 900

mg/day
 1,200

mg/day
 
Study 205 (n=396; n=303)
 
Total partial seizure frequency (median) % change
 -13%
 -23%
 -29%*
 -35%*
 
Responder rate (secondary endpoint)
 26%
 28%
 41%
 41%*
 
Study 301 (n=305; n=256)
 
Total partial seizure frequency (median) % change
 -18%
 ~
 ~
 -44%*
 
Responder rate
 23%
 ~
 ~
 56%*
 
Study 302 (n=538; n=471)
 
Total partial seizure frequency (median) % change
 -16%
 -28%*
 -40%*
 ~
Responder rate
 19%
 39%*
 47%*
 ~
* Statistically significant, p0.05

~ Dose not studied

In open-label extensions of the three placebo-controlled studies, persistence of efficacy was maintained over an eva luation period of at least 12 months (365 patients).

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with retigabine in paediatric patients aged 0 to below 2 years with Lennox Gastaut Syndrome.

The European Medicines Agency has defer