Systematic Review: Retigabine for Adjunctive Therapy in Partial Epilepsy

Study Overview
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Brief Summary
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There are a number of anti-epileptic drugs available for the treatment of partial onset seizures in patients with epilepsy. This study is a systematic review of the published literature on anti-epileptic drugs and is designed to compare the relative effectiveness and tolerability of a selection of them with retigabine. The drugs chosen for this comparison were lacosamide, pregabalin, tiagabine, zonisamide and eslicarbazepine. They were chosen because they belong to the newer generation of drugs for epilepsy (as does retigabine) and they have a similar license as well as having published data from studies that were conducted in similar patient populations with similar methods. GSK commissioned YHEC (York Health Economic Consortium) to carry out this review and analysis. YHEC identified relevant studies from international databases. These studies had compared one of the chosen anti-epileptic drugs with placebo. The results were pooled and combined in order to summarize the data for individual drugs as well to compare the results for different drugs with each other and with retigabine. Since none of the individual clinical studies compared one active drug with another, this systematic review is an indirect comparison of these drugs, using an established and recognised methodology which has well understood limitations.

Official Title
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Systematic Review: Retigabine for Adjunctive Therapy in Partial Epilepsy

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: retigabine/ezogabine
* Drug: lacosamide
* Drug: zonisamide
* Drug: pregabalin
* Drug: eslicarbazepine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have participated to a study that meets the following criteria: Be a study of retigabine, eslicarbazepine, lacosamide, zonisamide, pregabalin or tiagabine as an adjuvant therapy, compared to placebo or another drug; Be a randomized, placebo-controlled, add-on trial, or a parallel trial or cross-over trial in which data from the first treatment period could be treated as a parallel study; Have recruited patients with drug-resistant partial epilepsy (i.e., simple partial, complex partial, and/or secondarily generalised tonic-clonic seizures not controlled by at least 1 or more other AEDs); Have a maintenance treatment period of 8 weeks or longer, with a prospective baseline of minimum 4 weeks. Exclusion Criteria: N/A
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Drug-resistant (or refractory) partial epilepsy of all types<br>Drug-resistant (or refractory) partial epilepsy of all types | Drug: retigabine/ezogabine<br>* oral - all doses<br>* Other names: Trobalt (R); Potiga (R);Drug: lacosamide<br>* oral - all doses<br>* Other names: Vimpat;Drug: zonisamide<br>* oral - all doses<br>* Other names: Zonegran;Drug: pregabalin<br>* oral - all doses<br>* Other names: Lyrica;Drug: eslicarbazepine<br>* oral - all doses<br>* Other names: Zebinix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate | Proportion of patients who respond to treatment (50% reduction in seizure frequency from baseline) | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| Median Seizure reduction | Median percent reduction in seizure frequency from baseline | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| Seizure severity | Seizure severity (any definitions acceptable) | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| Time to onset of treatment effect | Time to onset of treatment effect | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| Seizure free patients | Proportion of patients who are seizure free (and time period over which this was measured) | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| Changes in HRQoL | Changes in HRQoL | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| All drop outs | Proportion of patients who drop out of the studies for any reason | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| Drop outs due to AE | Proportion of patients who drop out of the studies (as a result of adverse events i.e. tolerability) | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| Adverse events | Percentage of patients reporting 5 key adverse events identified by the Cochrane Epilepsy Group as common and important adverse effects of antiepileptic drugs: ataxia, dizziness, fatigue, nausea or somnolence | Duration of studies included in the systematic review up to 28 weeks of double blind period | 
| Mortality | Mortality | Duration of studies included in the systematic review up to 28 weeks of double blind period |