Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in Epilepsy

NCT ID: NCT00235755

Last Updated: 2017-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 539 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2008-04-30

Brief Summary

This Phase 3 study is being conducted to evaluate the efficacy and safety of retigabine dosed at 900 mg/day and 600 mg/day, in three equally divided doses, compared with placebo in patients with epilepsy who are receiving up to three established antiepileptic drugs (AEDs).

Detailed Description

This Phase 3 study is being conducted in Europe, Israel, Australia, and South Africa to evaluate the efficacy and safety of retigabine dosed at 900 mg/day and 600 mg/day, in three equally divided doses, compared with placebo in patients with epilepsy who are receiving up to three established antiepileptic drugs (AEDs). The primary objective is to demonstrate a superior change in total partial seizure frequency for four weeks from baseline to the double-blind period. The proportion of responders (greater than or equal to 50% reduction in seizure frequency for four weeks from baseline to the double-blind period) will also be evaluated.

Conditions

Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral tablet.

Retigabine 600 mg

Group Type: EXPERIMENTAL

Retigabine

Intervention Type: DRUG

Oral tablet. The starting daily dose will be 300 mg/day administered orally in three equally divided doses. This dosage will be increased by 150 mg/day (50 mg/dose) at 1-week intervals (titration phase). At the beginning of Week 3, patients will enter a 12 week maintenance phase.

Retigabine 900 mg

Group Type: EXPERIMENTAL

Retigabine

Intervention Type: DRUG

Oral tablet. The starting daily dose will be 300 mg/day administered orally in three equally divided doses. This dosage will be increased by 150 mg/day (50 mg/dose) at 1-week intervals (titration phase). At the beginning of Week 5, patients will enter a 12 week maintenance phase.

Interventions

Retigabine

Oral tablet. The starting daily dose will be 300 mg/day administered orally in three equally divided doses. This dosage will be increased by 150 mg/day (50 mg/dose) at 1-week intervals (titration phase). At the beginning of Week 3, patients will enter a 12 week maintenance phase.

Intervention Type: DRUG

Retigabine

Oral tablet. The starting daily dose will be 300 mg/day administered orally in three equally divided doses. This dosage will be increased by 150 mg/day (50 mg/dose) at 1-week intervals (titration phase). At the beginning of Week 5, patients will enter a 12 week maintenance phase.

Intervention Type: DRUG

Placebo

Oral tablet.

Intervention Type: DRUG

Other Intervention Names

GKE-841; D-23129; GKE-841; D-23129

Eligibility Criteria

Inclusion Criteria

• Diagnosis of refractory epilepsy with simple or complex partial onset seizures with or without secondary generalization
• 28-day partial seizure frequency rate of four or more partial seizures over the 8-week baseline phase
• Currently treated with up to three established AEDs
• Vagal Nerve Stimulator may be included

Exclusion Criteria

• Existing medical or psychiatric condition which could affect patient's health or compromise ability to participate in the study
• Clinically significant abnormalities on physical exam, vital signs, ECG, or liver function tests
• Impaired renal function (creatinine clearance less than 50 mL/minute)
• Evidence of progressive central nervous disease, lesion, or encephalopathy
• History of primary generalized seizures
• History of clustering or flurries or status epilepticus within 12 months of study entry

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bausch Health Americas, Inc.

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Neurological Clinic-Texas

Dallas, Texas, United States

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

North Coast Neurology Centre

Maroochydore, Queensland, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Austin & Repatriation Medical Centre

West Heidelberg, Victoria, Australia

A. Z. Middelheim -- Department of Neurology

Antwerp, , Belgium

AZ Sint-Jan

Bruges, , Belgium

Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology

Leuven, , Belgium

Centre Neurologique William Lennox

Ottignies, , Belgium

Hopital Neurologique Pierre Wertheimer

Lyon, Lyonnais, France

CHU Pontchaillou

Rennes, , France

Hopital Civil de Strasbourg

Strasbourg, , France

Centre Medical de La Teppe

Tain-l'Hermitage, , France

University of Bonn -- Department for Epileptplogy

Bonn, , Germany

Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen

Erlangen, , Germany

Georg-August-Universitaet Goettingen

Göttingen, , Germany

Universitaetsklinik Mainz Neurologische Klinik

Mainz, , Germany

Universitaet Giessen / Marburg Neurologie

Marburg, , Germany

Theatinerstrasse 44

Munich, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

Natl. Inst. of Psychiatry and Neurology

Budapest, , Hungary

Orszagos Idegsebeszeti Tudomanyos Intezet

Budapest, , Hungary

Barzilai Medical Center

Ashkelon, , Israel

Assaf Harofeh Medical Center

Beer Yaakov, , Israel

Rambam Medical Center

Haifa, , Israel

Wolfson Medical Center

Holon, , Israel

Western Galilee Hospital

Nahariya, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Kaplan Medical Center

Rehovot, , Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Specjalistyczna Przychodnia Lekarska Medikard

Padlewskiego 4, Plock, Poland

NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"

Bialystok, , Poland

Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika

Gdansk, , Poland

Katedra i Klinika Neurologii Slaskiej Akademii Medycznej

Katowice, , Poland

WSS im.Kardynala S. Wyszynskiego

Lublin, , Poland

Instytut Psychiatrii i Neurologii II Oddzial Neurologii

Warsaw, , Poland

Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"

Warsaw, , Poland

Interregional Clinical Diagnostic Centre

Kazan', , Russia

City Hospital # 1

Moscow, , Russia

Clinic of Nervous Diseases of Sechenov's Moscow Med. Academy

Moscow, , Russia

District Antiepileptic Centre City Clinical Hospital # 71

Moscow, , Russia

Military Medical Academy n.a. S.M.Kirov

Saint Petersburg, , Russia

St.Petersburg State Medical University n.a. I.P.Pavlov

Saint Petersburg, , Russia

Triple M Research

Port Elizabeth, East Cape, South Africa

University of the Free State

Bloemfontein, Gauteng, South Africa

Wilgers MR & Medical Centre

Pretoria, Gauteng, South Africa

Sunninghill & Kopano Clinical Trials

Sunninghill, Gauteng, South Africa

Johannesburg Hospital

Johannesburg, Gauten, South Africa

Inkosi Albert Luthuli Central Hospital

Durban, KwaZulu-Natal, South Africa

Carl Bremer Hospital

Belville, West Cape, South Africa

Groote Schuur Hospital

Cape Town, Western Cape, South Africa

Panorama Medi-Clinic

Cape Town, , South Africa

Hospital de La Santa Creu i Sant Pau

Barcelona, , Spain

Hospital de Cruces

Bilbao, , Spain

Hosp de Donostia

Donostia / San Sebastian, , Spain

Hosp. Virgen de las Nieves

Granada, , Spain

Hospital Ruber Internacional de Madrid

Madrid, , Spain

Hosp. Clinico Univ. Lozano Blesa

Zaragoza, , Spain

Psychosomatic Center of Dnepropetr. Regional Clinic

Dnipro, , Ukraine

Kharkiv State Medical University

Kharkiv, , Ukraine

Institute of Neurology, Psychiatry and Narcology of AMS, Ukr

Kharkiv, , Ukraine

Epilepsy Center of Municipal Clinical Psychoneurological Hospital

Kiev, , Ukraine

Odessa Regional Clinical Hospital

Odesa, , Ukraine

The James Cook University Hospital

Middlesbrough, Mersyd, United Kingdom

Fylde Coast Hospital

Blackpool, , United Kingdom

Western Infirmary (Epilepsy)

Glasgow, , United Kingdom

Walton Centre for Neurology & Neurosurgery

Liverpool, , United Kingdom

Royal London Hospital

London, , United Kingdom

Countries

United States; Australia; Belgium; France; Germany; Hungary; Israel; Poland; Russia; South Africa; Spain; Ukraine; United Kingdom

References

Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, Nohria V, Mansbach H; RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology. 2010 Nov 16;75(20):1817-24. doi: 10.1212/WNL.0b013e3181fd6170. Epub 2010 Oct 13.

Reference Type: BACKGROUND

PMID: 20944074 (View on PubMed)

Tompson DJ, Crean CS. Clinical pharmacokinetics of retigabine/ezogabine. Curr Clin Pharmacol. 2013 Nov;8(4):319-31. doi: 10.2174/15748847113089990053.

Reference Type: BACKGROUND

PMID: 23342983 (View on PubMed)

Brickel N, Gandhi P, VanLandingham K, Hammond J, DeRossett S. The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels. Epilepsia. 2012 Apr;53(4):606-12. doi: 10.1111/j.1528-1167.2012.03441.x. Epub 2012 Mar 16.

Reference Type: BACKGROUND

PMID: 22428574 (View on PubMed)

Porter RJ, Burdette DE, Gil-Nagel A, Hall ST, White R, Shaikh S, DeRossett SE. Retigabine as adjunctive therapy in adults with partial-onset seizures: integrated analysis of three pivotal controlled trials. Epilepsy Res. 2012 Aug;101(1-2):103-12. doi: 10.1016/j.eplepsyres.2012.03.010. Epub 2012 Apr 16.

Reference Type: DERIVED

PMID: 22512894 (View on PubMed)

Study Documents

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

VRX-RET-E22-302

Identifier Type: -

Identifier Source: org_study_id