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

NCT00235755 | Completed Phase 3 Results

• 1 other identifier: VRX-RET-E22-302
• Study Type: interventional
• Target: 539
• Locations: 13 countries
• Sites: 70

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).

Conditions

Seizures

Keywords

Partial Seizures; Complex Partial Seizures; Epilepsy; Potassium Channels; Anticonvulsant

Outcome Measures

Primary Outcomes (2)

• Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases)

  28-day total PS (PSs \[also called focal seizures\] are seizures limited to a specific area of the brain) frequency in the BL period = (Number \[No.\] of total PSs reported in the BL period divided by the No. of days of available total PS data in the BL period) x 28 days. 28-day total PS frequency in the DB period = (No. of total PSs reported in the DB period divided by the No. of days of available total PS data in the DB period) x 28 days. Percent change = (\[value in the DB period minus value at BL\] divided by the BL value) x 100%. Negative valu es indicate a reduction in seizure frequency.

  Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)

• Number of Participants Classified as Responders and Non-responders During the Maintenance Phase

  Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the Maintenance Phase as compared to the Baseline period.

  Week 5 through Week 16

Secondary Outcomes (18)

• Number of Participants Who Were Responders and Non-responders During the DB Phase

  Week 1 through Week 16

• Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase

  Baseline (Week -7 through Week 0), Week 5 through Week 16

• Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories

  Baseline (Week -7 through Week 0), Week 1 through Week 16

• Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories

  Baseline (Week -7 through Week 0), Week 1 through Week 16

• Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase

  Baseline (Week -7 through Week 0), Week 5 through Week 16

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Retigabine 600 mg

EXPERIMENTAL

Drug: Retigabine

Retigabine 900 mg

EXPERIMENTAL

Drug: Retigabine

Interventions

Retigabine 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.

Also known as: GKE-841, D-23129

Retigabine 600 mg

Placebo DRUG

Oral tablet.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of refractory epilepsy with simple or complex partial onset seizures with or without secondary generalization
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (70)

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Neurological Clinic-Texas

Dallas, Texas, 75230, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

North Coast Neurology Centre

Maroochydore, Queensland, 4558, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Austin & Repatriation Medical Centre

West Heidelberg, Victoria, 3084, Australia

Location

A. Z. Middelheim -- Department of Neurology

Antwerp, 2020, Belgium

Location

AZ Sint-Jan

Bruges, 8000, Belgium

Location

Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology

Leuven, 3000, Belgium

Location

Centre Neurologique William Lennox

Ottignies, 1340, Belgium

Location

Hopital Neurologique Pierre Wertheimer

Lyon, Lyonnais, 69003, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

Hopital Civil de Strasbourg

Strasbourg, 67 67091, France

Location

Centre Medical de La Teppe

Tain-l'Hermitage, 26 26600, France

Location

University of Bonn -- Department for Epileptplogy

Bonn, D-53105, Germany

Location

Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen

Erlangen, BY 91054, Germany

Location

Georg-August-Universitaet Goettingen

Göttingen, NI 37075, Germany

Location

Universitaetsklinik Mainz Neurologische Klinik

Mainz, RP 55101, Germany

Location

Universitaet Giessen / Marburg Neurologie

Marburg, HE 35033, Germany

Location

Theatinerstrasse 44

Munich, BY 80333, Germany

Location

Universitaetsklinikum Ulm

Ulm, BW 89081, Germany

Location

Natl. Inst. of Psychiatry and Neurology

Budapest, 1021, Hungary

Location

Orszagos Idegsebeszeti Tudomanyos Intezet

Budapest, 1145, Hungary

Location

Barzilai Medical Center

Ashkelon, 78306, Israel

Location

Assaf Harofeh Medical Center

Beer Yaakov, 70300, Israel

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Wolfson Medical Center

Holon, 58100, Israel

Location

Western Galilee Hospital

Nahariya, 22100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Specjalistyczna Przychodnia Lekarska Medikard

Padlewskiego 4, Plock, 09-402, Poland

Location

NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"

Bialystok, 15-420, Poland

Location

Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika

Gdansk, 80-803, Poland

Location

Katedra i Klinika Neurologii Slaskiej Akademii Medycznej

Katowice, 40-752, Poland

Location

WSS im.Kardynala S. Wyszynskiego

Lublin, 20-718, Poland

Location

Instytut Psychiatrii i Neurologii II Oddzial Neurologii

Warsaw, 02-957, Poland

Location

Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"

Warsaw, 03-464, Poland

Location

Interregional Clinical Diagnostic Centre

Kazan', 420048, Russia

Location

City Hospital # 1

Moscow, 117049, Russia

Location

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

Moscow, 119021, Russia

Location

District Antiepileptic Centre City Clinical Hospital # 71

Moscow, 121374, Russia

Location

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

Saint Petersburg, 194044, Russia

Location

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

Saint Petersburg, 197022, Russia

Location

Triple M Research

Port Elizabeth, East Cape, 6001, South Africa

Location

University of the Free State

Bloemfontein, Gauteng, 9300, South Africa

Location

Wilgers MR & Medical Centre

Pretoria, Gauteng, 0041, South Africa

Location

Sunninghill & Kopano Clinical Trials

Sunninghill, Gauteng, 2157, South Africa

Location

Johannesburg Hospital

Johannesburg, Gauten, 2193, South Africa

Location

Inkosi Albert Luthuli Central Hospital

Durban, KwaZulu-Natal, 4091, South Africa

Location

Carl Bremer Hospital

Belville, West Cape, 7531, South Africa

Location

Groote Schuur Hospital

Cape Town, Western Cape, 7925, South Africa

Location

Panorama Medi-Clinic

Cape Town, 7550, South Africa

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital de Cruces

Bilbao, 48903, Spain

Location

Hosp de Donostia

Donostia / San Sebastian, 20014, Spain

Location

Hosp. Virgen de las Nieves

Granada, 18013, Spain

Location

Hospital Ruber Internacional de Madrid

Madrid, 28034, Spain

Location

Hosp. Clinico Univ. Lozano Blesa

Zaragoza, 50009, Spain

Location

Psychosomatic Center of Dnepropetr. Regional Clinic

Dnipro, 49616, Ukraine

Location

Kharkiv State Medical University

Kharkiv, 61022, Ukraine

Location

Institute of Neurology, Psychiatry and Narcology of AMS, Ukr

Kharkiv, 61068, Ukraine

Location

Epilepsy Center of Municipal Clinical Psychoneurological Hospital

Kiev, 04080, Ukraine

Location

Odessa Regional Clinical Hospital

Odesa, 65025, Ukraine

Location

The James Cook University Hospital

Middlesbrough, Mersyd, T&W TS4 3BW, United Kingdom

Location

Fylde Coast Hospital

Blackpool, LANARK FY3 8BP, United Kingdom

Location

Western Infirmary (Epilepsy)

Glasgow, G11 6NT, United Kingdom

Location

Walton Centre for Neurology & Neurosurgery

Liverpool, L9 7LJ, United Kingdom

Location

Royal London Hospital

London, GT LON E1 1BB, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 20944074 BACKGROUND

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

  PMID: 23342983 BACKGROUND

• 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.

  PMID: 22428574 BACKGROUND

• 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.

  PMID: 22512894 DERIVED

Related Links

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

MeSH Terms

Conditions

Seizures; Epilepsy

Interventions

ezogabine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2005
• First Posted: October 10, 2005
• Study Start: December 1, 2005
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: April 21, 2017
• Results First Posted: November 7, 2011

Record last verified: 2017-03

Locations

PL (7); FR (4); ZA (9); IL (8); GB (5); HU (2); UA (5); AU (5); RU (6); BE (4); ES (6); DE (7); US (2)