A novel design for a dose finding, safety, and drug interaction study of an antiepileptic drug (retigabine) in early clinical development.

Objective: To obtain information on the acceptable doses of the antiepileptic drug (AED) retigabine (RTG), the maximum tolerated dose (MTD), drug interactions, safety and tolerability, and preliminary evidence of efficacy when administered as adjunctive therapy and as monotherapy.

Materials: Study 202 was an open-label, add-on study in patients with partial or generalized epilepsy treated with valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), or topiramate (TPM) as monotherapy. Following baseline assessments, patients entered a dose titration phase of 28 – 56 days.

Adjunctive use of ezogabine/retigabine with either traditional sodium channel blocking antiepileptic drugs (AEDs) or AEDs with other mechanisms of action: Evaluation of efficacy and tolerability.

Integrated data from three double-blind, randomized, placebo-controlled trials were analyzed to evaluate the efficacy and tolerability of ezogabine (EZG; US adopted name)/retigabine (RTG; international non-proprietary name) when used in combination with ≥1 sodium channel blocking antiepileptic drug (AED), ≥1 non-sodium channel blocking AED, or ≥1 AED from both the sodium channel and non-sodium channel mechanistic groups. Efficacy and tolerability appeared to be similar across all three groups of patients.

Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.

Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated potassium-channel KCNQ2-5 (Kv 7.2-7.5) opening.

Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy.

Objective: To evaluate the efficacy and safety of ezogabine (United States adopted name)/retigabine (international nonproprietary name) (EZG[RTG]) 1,200 mg/day as adjunctive treatment in adults with drug-resistant epilepsy with partial-onset seizures with or without secondary generalization.

Methods: RESTORE 1 was a multicenter, randomized, double-blind, parallel-group trial. Following a prospective 8-week baseline phase, patients entered an 18-week double-blind treatment period (6-week forced dose titration to EZG[RTG] 1,200 mg/day in 3 equally divided doses or placebo, followed by a 12-week maintenance phase).