Systematic Review: Retigabine for Adjunctive Therapy in Partial Epilepsy

Completed

• Conditions: Epilepsy
• Interventions: Drug: retigabine/ezogabine; Drug: lacosamide; Drug: zonisamide; Drug: pregabalin; Drug: eslicarbazepine

• Registration Number: NCT01587339
• Lead Sponsor: GlaxoSmithKline

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09
• Primary Completion: 2011-03
• Study Completion: 2011-07
• Study First Submitted: 2012-04-26
• Study First Submitted QC: 2012-04-26
• Study First Posted: 2012-04-30
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-12
• Last Update Posted: 2013-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6498

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Drug-resistant (or refractory) partial epilepsy of all types	retigabine/ezogabine	Drug-resistant (or refractory) partial epilepsy of all types
Drug-resistant (or refractory) partial epilepsy of all types	lacosamide	Drug-resistant (or refractory) partial epilepsy of all types
Drug-resistant (or refractory) partial epilepsy of all types	zonisamide	Drug-resistant (or refractory) partial epilepsy of all types
Drug-resistant (or refractory) partial epilepsy of all types	pregabalin	Drug-resistant (or refractory) partial epilepsy of all types
Drug-resistant (or refractory) partial epilepsy of all types	eslicarbazepine	Drug-resistant (or refractory) partial epilepsy of all types

Primary Outcome Measures

Name	Time	Method
Responder Rate	Duration of studies included in the systematic review up to 28 weeks of double blind period	Proportion of patients who respond to treatment (50% reduction in seizure frequency from baseline)
Median Seizure reduction	Duration of studies included in the systematic review up to 28 weeks of double blind period	Median percent reduction in seizure frequency from baseline
Seizure severity	Duration of studies included in the systematic review up to 28 weeks of double blind period	Seizure severity (any definitions acceptable)
Time to onset of treatment effect	Duration of studies included in the systematic review up to 28 weeks of double blind period	Time to onset of treatment effect
Seizure free patients	Duration of studies included in the systematic review up to 28 weeks of double blind period	Proportion of patients who are seizure free (and time period over which this was measured)
Changes in HRQoL	Duration of studies included in the systematic review up to 28 weeks of double blind period	Changes in HRQoL
Drop outs due to AE	Duration of studies included in the systematic review up to 28 weeks of double blind period	Proportion of patients who drop out of the studies (as a result of adverse events i.e. tolerability)
All drop outs	Duration of studies included in the systematic review up to 28 weeks of double blind period	Proportion of patients who drop out of the studies for any reason
Adverse events	Duration of studies included in the systematic review up to 28 weeks of double blind period	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
Mortality	Duration of studies included in the systematic review up to 28 weeks of double blind period	Mortality