An Open-Label, Flexible-Dose Study of Retigabine Immediate Release (IR) as Adjunctive Therapy to Specified Monotherapy Antiepileptic Treatments in Adults with Partial-Onset Seizures (RGB113905)

Epilepsy affects approximately 50 million people worldwide. Currently available
antiepileptic drugs (AEDs) provide satisfactory seizure control in
approximately 70% of patients; however, the remaining 30% of epilepsy patients
are refractory to treatment. The partial-onset seizure is the most common type
of seizure that is uncontrolled in adult patients.
The introduction of new AEDs during the last decade has increased therapeutic
possibilities. However, none of the newer AEDs provides adequate seizure
control in all patients. The treatment of patients who do not respond
adequately to current AEDs remains a problem and motivates the continued search
for compounds with good efficacy and an acceptable safety and tolerability
profile.
Retigabine is a novel antiepileptic compound with well-documented
anticonvulsant properties. Retigabine has a primary pharmacological action that
is unlike currently available antiepileptic drugs (AEDs).
Retigabine has been shown to be superior to placebo as adjunctive therapy in
subjects with partial-onset epilepsy.
The RCTs involved strict selection criteria and also mandated titration to one
of three fixed doses. In these studies, in about 70% of cases, retigabine was
an add-on to two or more AEDs.
This Phase IIIb study is a hypothesis generating investigation to gain insight
into efficacy, safety and tolerability, and health outcomes of retigabine as
adjunctive therapy to specified monotherapy AED treatments using a flexible
dosing regimen in adult subjects with partial-onset seizures.

Primary: To evaluate the efficacy of retigabine as adjunctive therapy to each
of the following specified monotherapy AED treatments: carbamazepine/
oxcarbazepine, lamotrigine, levetiracetam or valproic acid in subjects with
partial-onset seizures (POS) using a flexible dosing regimen.
Secondary: Efficacy in the pooled set of specified AED treatments. Safety and
tolerability with each and in the pooled set of monotherapy AED treatments.
Effect with each and in the pooled set of the specified monotherapy AED
treatments on functional status and productivity.

Open-label, non-comparative phase III study:
* Screening and 8 week baseline evaluation with continuation of existing
monotherapy AED.
* Start with retigabine 150 mg/day, gradual dose increase in the 1st 4 weeks to
600 mg/day. Continuation of existing AED, dose not to be changed.
* 16 week period with flexible dosing of retigabine (in principle 300-1200
mg/day) and of existing AED.
* Possibility to participate in follow-up study or gradual discontinuation of
retigabine in 3 weeks.
Approx. 235 patients.

Treatment with retigabine.

Risks: Adverse effects of study medication.
Burden: 7-8 visits in 33 weeks. 2-3x vital signs, 2x physical and neurological
examination, 6-7x blood tests (50 ml total), 6-7x pregnancy test (if relevant),
4-5x ECG, 6-7x 1-2 questionnaires (incl. questions about mental condition and
suicide thoughts), 2x bladder ultrasound.
Diaries during entire period (medication intake and seizure calendar).