Clinical trial NCT00235755: Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in Epilepsy
Official title: Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase 3 Study - Determine Efficacy and Safety of Two Doses of Retigabine (900 Mg/Day and 600 Mg/Day) Used as Adjunctive Therapy in Refractory Epilepsy Patients With Partial-Onset Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Seizures
Keywords: Partial Seizures
Complex Partial Seizures
Epilepsy
Potassium Channels
Anticonvulsant
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Bausch Health Americas, Inc.
First posted: 2005-10-10
Enrollment: 539
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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)
timeFrame: Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)
measure: Number of Participants Classified as Responders and Non-responders During the Maintenance Phase
timeFrame: Week 5 through Week 16
Secondary outcomes:
measure: Number of Participants Who Were Responders and Non-responders During the DB Phase
timeFrame: Week 1 through Week 16
measure: Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
timeFrame: Baseline (Week -7 through Week 0), Week 5 through Week 16
measure: 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
timeFrame: Baseline (Week -7 through Week 0), Week 1 through Week 16
measure: 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
timeFrame: Baseline (Week -7 through Week 0), Week 1 through Week 16
measure: Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
timeFrame: Baseline (Week -7 through Week 0), Week 5 through Week 16
measure: Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase
timeFrame: Baseline (Week -7 through Week 0), Week 5 through Week 16
measure: Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline
timeFrame: Baseline (Week -7 through Week 0), Week 1 through Week 16
measure: Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
timeFrame: Week 1 through Week 16
measure: Number of Participants Who Were Seizure-free During the Maintenance Phase
timeFrame: Week 5 through Week 16
measure: Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
timeFrame: Week 1 through Week 16
measure: Percentage of Seizure-free Days During the Maintenance Phase
timeFrame: Week 5 through Week 16
measure: Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
timeFrame: Week 16/end of treatment phase
measure: Patient Global Impression (PGI) Score at the End of the Maintenance Phase
timeFrame: Week 16/end of treatment phase
measure: Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16
timeFrame: End of Baseline (Week 0), Weeks 4, 8, and 16
measure: Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
timeFrame: Week 1 through Week 16
measure: Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
timeFrame: Week 1 through Week 16
measure: Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase
timeFrame: Baseline (Week -7 through 0), Weeks 8 and 16
measure: Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase
timeFrame: Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 of Maintenance Phase
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Dallas
country: United States
facility: Neurological Clinic-Texas
state: Texas
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Maroochydore
country: Australia
facility: North Coast Neurology Centre
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: West Heidelberg
country: Australia
facility: Austin & Repatriation Medical Centre
state: Victoria
city: Antwerp
country: Belgium
facility: A. Z. Middelheim -- Department of Neurology
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology
city: Ottignies
country: Belgium
facility: Centre Neurologique William Lennox
city: Lyon
country: France
facility: Hopital Neurologique Pierre Wertheimer
state: Lyonnais
city: Rennes Cedex
country: France
facility: CHU Pontchaillou
city: Strasbourg
country: France
facility: Hopital Civil de Strasbourg
city: Tain L'Hermitage
country: France
facility: Centre Medical de La Teppe
city: Bonn
country: Germany
facility: University of Bonn -- Department for Epileptplogy
city: Erlangen
country: Germany
facility: Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen
city: Goettingen
country: Germany
facility: Georg-August-Universitaet Goettingen
city: Mainz
country: Germany
facility: Universitaetsklinik Mainz Neurologische Klinik
city: Marburg
country: Germany
facility: Universitaet Giessen / Marburg Neurologie
city: Munich
country: Germany
facility: Theatinerstrasse 44
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Budapest
country: Hungary
facility: Natl. Inst. of Psychiatry and Neurology
city: Budapest
country: Hungary
facility: Orszagos Idegsebeszeti Tudomanyos Intezet
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Beer Yaakov
country: Israel
facility: Assaf Harofeh Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Nahariya
country: Israel
facility: Western Galilee Hospital
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Rechovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Padlewskiego 4
country: Poland
facility: Specjalistyczna Przychodnia Lekarska Medikard
state: Plock
city: Bialystok
country: Poland
facility: NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"
city: Gdansk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika
city: Katowice
country: Poland
facility: Katedra i Klinika Neurologii Slaskiej Akademii Medycznej
city: Lublin
country: Poland
facility: WSS im.Kardynala S. Wyszynskiego
city: Warsaw
country: Poland
facility: Instytut Psychiatrii i Neurologii II Oddzial Neurologii
city: Warsaw
country: Poland
facility: Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"
city: Kazan
country: Russian Federation
facility: Interregional Clinical Diagnostic Centre
city: Moscow
country: Russian Federation
facility: City Hospital # 1
city: Moscow
country: Russian Federation
facility: Clinic of Nervous Diseases of Sechenov's Moscow Med. Academy
city: Moscow
country: Russian Federation
facility: District Antiepileptic Centre City Clinical Hospital # 71
city: St. Petersburg
country: Russian Federation
facility: Military Medical Academy n.a. S.M.Kirov
city: St. Petersburg
country: Russian Federation
facility: St.Petersburg State Medical University n.a. I.P.Pavlov
city: Port Elizabeth
country: South Africa
facility: Triple M Research
state: East Cape
city: Bloemfontein
country: South Africa
facility: University of the Free State
state: Gauteng
city: Pretoria
country: South Africa
facility: Wilgers MR & Medical Centre
state: Gauteng
city: Sunninghill
country: South Africa
facility: Sunninghill & Kopano Clinical Trials
state: Gauteng
city: Johannesburg
country: South Africa
facility: Johannesburg Hospital
state: Gauten
city: Durban
country: South Africa
facility: Inkosi Albert Luthuli Central Hospital
state: KwaZulu-Natal
city: Belville
country: South Africa
facility: Carl Bremer Hospital
state: West Cape
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
state: Western Cape
city: Cape Town
country: South Africa
facility: Panorama Medi-Clinic
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Bilbao
country: Spain
facility: Hospital de Cruces
city: Granada
country: Spain
facility: Hosp. Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital Ruber Internacional de Madrid
city: San Sebastian
country: Spain
facility: Hosp de Donostia
city: Zaragoza
country: Spain
facility: Hosp. Clinico Univ. Lozano Blesa
city: Dnepropetrovsk
country: Ukraine
facility: Psychosomatic Center of Dnepropetr. Regional Clinic
city: Kharkiv
country: Ukraine
facility: Kharkiv State Medical University
city: Kharkov
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of AMS, Ukr
city: Kiev
country: Ukraine
facility: Epilepsy Center of Municipal Clinical Psychoneurological Hospital
city: Odessa
country: Ukraine
facility: Odessa Regional Clinical Hospital
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
state: Mersyd
city: Blackpool
country: United Kingdom
facility: Fylde Coast Hospital
city: Glasgow
country: United Kingdom
facility: Western Infirmary (Epilepsy)
city: Liverpool
country: United Kingdom
facility: Walton Centre for Neurology & Neurosurgery
city: London
country: United Kingdom
facility: Royal London Hospital
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Tompson DJ, Crean CS. Clinical pharmacokinetics of retigabine/ezogabine. Curr Clin Pharmacol. 2013 Nov;8(4):319-31. doi: 10.2174/15748847113089990053.
citation: 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.
citation: 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.