Systematic Review: Retigabine for Adjunctive Therapy in Partial Epilepsy

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: retigabine/ezogabine; Drug: lacosamide; Drug: zonisamide; Drug: pregabalin; Drug: eslicarbazepine

• Study Type: Observational
• Enrollment (Actual): 6498

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We included published papers on studies that had recruited drug-resistant (or refractory) partial epilepsy of all types

Description

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 Plan

How is the study designed?

Design Details

• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Drug-resistant (or refractory) partial epilepsy of all types	Drug: retigabine/ezogabine; oral - all doses; Other Names: Trobalt (R); Potiga (R); Drug: lacosamide; oral - all doses; Other Names: Vimpat; Drug: zonisamide; oral - all doses; Other Names: Zonegran; Drug: pregabalin; oral - all doses; Other Names: Lyrica; Drug: eslicarbazepine; oral - all doses; Other Names: Zebinix

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Martyn-St James M, Glanville J, McCool R, Duffy S, Cooper J, Hugel P, Lane PW. The efficacy and safety of retigabine and other adjunctive treatments for refractory partial epilepsy: a systematic review and indirect comparison. Seizure. 2012 Nov;21(9):665-78. doi: 10.1016/j.seizure.2012.07.011. Epub 2012 Aug 14.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: April 26, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 30, 2012

Study Record Updates

• Last Update Posted (Estimate): September 16, 2013
• Last Update Submitted That Met QC Criteria: September 12, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin; Lacosamide; Eslicarbazepine acetate; Zonisamide; Ezogabine
• Other Study ID Numbers: 115049

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No