Last updated: 11/04/2018 13:40:24
Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in EpilepsyRESTORE2
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
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)
Number of participants classified as responders and non-responders during the Maintenance Phase
Timeframe: Week 5 through Week 16
Secondary outcomes:
Number of participants who were responders and non-responders during the DB Phase
Timeframe: Week 1 through Week 16
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
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
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
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
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
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
Number of participants who were seizure-free during the DB Phase (Titration and Maintenance Phases)
Timeframe: Week 1 through Week 16
Number of participants who were seizure-free during the Maintenance Phase
Timeframe: Week 5 through Week 16
Percentage of seizure-free days during the DB Phase (Titration and Maintenance Phases)
Timeframe: Week 1 through Week 16
Percentage of seizure-free days during the Maintenance Phase
Timeframe: Week 5 through Week 16
Clinical Global Impression-Improvement (CGI-I) score at the end of the Maintenance Phase
Timeframe: Week 16/end of treatment phase
Patient Global Impression (PGI) score at the end of the Maintenance Phase
Timeframe: Week 16/end of treatment phase
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
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
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
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
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
Interventions:
Drug: Retigabine
Drug: Placebo
Enrollment:
539
Observational study model:
Not applicable
Primary completion date:
2008-30-04
Time perspective:
Not applicable
Clinical publications:
Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, Nohria V, Mansbach H; On behalf of the RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology. 2010;75(20):1817-24. Epub 2010 Oct 13.
Debra J. Tompson and Christopher S. Crean. Clinical Pharmacokinetics of Retigabine/Ezogabine. Curr Clin Pharmacol. 2013;
Neil Brickel, Paul Gandhi, Kevan VanLandingham, Janet Hammond, Sarah DeRossett. The urinary safety profile and secondary renal effects of retigabine (ezogabine): A first-in-class antiepileptic drug that targets KCNQ (Kv7) potassium channels . Epilepsia. 2012;53(4):606-612.
Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, Nohria V, Mansbach H; On behalf of the RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology. 2010;75(20):1817-24.
Debra J. Tompson and Christopher S. Crean. Clinical Pharmacokinetics of Retigabine/Ezogabine. Curr Clin Pharmacol. 2013;8(4):319-331.
Debra J. Tompson and Christopher S. Crean. The Interaction Potential of Retigabine (Ezogabine) with other Antiepileptic Drugs . Curr Clin Pharmacol. 2014;9(2):148-56.
Debra J. Tompson, Christopher S. Crean, Russell Reeve, N. Seth Berry. Efficacy and Tolerability Exposure–Response Relationship of Retigabine (Ezogabine) Immediate-Release Tablets in Patients with Partial-Onset Seizures. Clin Ther. 2013;35(8):1174-1185.e4.
Martin J Brodie, Jacqueline A French, Susan McDonald, Wen-Jene Lee, Bryan Adams, Andrew Scott, Virinder Nohria, Sarah DeRossettu. Adjunctive Use of Retigabine with either Traditional Sodium Channel Blocker Antiepileptic Drugs (AEDs) or AEDs with other Mechanisms of Action: Evaluation of Safety, Tolerability and Efficacy. Epilepsy Res. 2014;
R. J. Porter, D. E. Burdette, A. Gil-Nagel, S. T. Hall, R. White, S. Shaikh, S. E. DeRossett . Retigabine as adjunctive therapy in adults with partial-onset epilepsy: Integrated analysis of three pivotal controlled trials. Epilepsy Res. 2012;101:103-112.
Medical condition
Seizures
Product
retigabine, ezogabine
Collaborators
Valeant
Study date(s)
December 2005 to April 2008
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18 - 75 years
Accepts healthy volunteers
No
- 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
- 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
Inclusion and exclusion 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
Trial location(s)
Location
Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology
Leuven, Belgium, 3000
Status
Study Complete
Location
Instytut Psychiatrii i Neurologii II Oddzial Neurologii
Warsaw, Poland, 02-957
Status
Study Complete
Location
Universitaetsklinik Mainz Neurologische Klinik
Mainz, Germany, RP 55101
Status
Study Complete
Location
Inkosi Albert Luthuli Central Hospital
Durban, KwaZulu-Natal, South Africa, 4091
Status
Study Complete
Location
Natl. Inst. of Psychiatry and Neurology
Budapest, Hungary, 1021
Status
Study Complete
Location
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Status
Study Complete
Location
St.Petersburg State Medical University n.a. I.P.Pavlov
St. Petersburg, Russia, 197022
Status
Study Complete
Location
Sunninghill & Kopano Clinical Trials
Sunninghill, Gauteng, South Africa, 2157
Status
Study Complete
Location
A. Z. Middelheim -- Department of Neurology
Antwerp, Belgium, 2020
Status
Study Complete
Location
Georg-August-Universitaet Goettingen
Goettingen, Germany, NI 37075
Status
Study Complete
Location
Oddzial Neurologii -- Klinika Neurologii ICZMP
U1. Parzeczewska 35, Zgierz, Poland, 95-100
Status
Terminated/Withdrawn
Location
Westfaelische-Wilhelms-Universitaet Muenster
Muenster, Germany, NI 37075
Status
Terminated/Withdrawn
Location
University of the Free State
Bloemfontein, Gauteng, South Africa, 9300
Status
Study Complete
Location
Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika
Gdansk, Poland, 80-803
Status
Study Complete
Location
Triple M Research
Port Elizabeth, East Cape, South Africa, 6001
Status
Study Complete
Location
The James Cook University Hospital
Middlesbrough, MERSYD, United Kingdom, T&W TS4 3BW
Status
Study Complete
Location
Specjalistyczna Przychodnia Lekarska Medikard
Padlewskiego 4, Plock, Poland, 09-402
Status
Study Complete
Location
Pecs University of Science, Clinic of Neurology
Pecs, Ret, Hungary, U2
Status
Terminated/Withdrawn
Location
Military Medical Academy n.a. S.M.Kirov
St. Petersburg, Russia, 194044
Status
Study Complete
Location
Epilepsy Center of Municipal Clinical Psychoneurological Hospital
Kiev, Ukraine, 04080
Status
Study Complete
Location
Groote Schuur Hospital
Cape Town, Western Cape, South Africa, 7925
Status
Study Complete
Location
Universitaet Giessen / Marburg Neurologie
Marburg, Germany, HE 35033
Status
Study Complete
Location
Psychosomatic Center of Dnepropetr. Regional Clinic
Dnepropetrovsk, Ukraine, 49616
Status
Study Complete
Location
NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"
Bialystok, Poland, 15-420
Status
Study Complete
Location
Wilgers MR & Medical Centre
Pretoria, Gauteng, South Africa, 0041
Status
Study Complete
Location
Katedra i Klinika Neurologii Slaskiej Akademii Medycznej
Katowice, Poland, 40-752
Status
Study Complete
Location
North Coast Neurology Centre
Maroochydore, Queensland, Australia, 4558
Status
Study Complete
Location
Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"
Warsaw, Poland, 03-464
Status
Study Complete
Location
University of Bonn -- Department for Epileptplogy
Bonn, Germany, D-53105
Status
Study Complete
Location
Orszagos Idegsebeszeti Tudomanyos Intezet
Budapest, Hungary, 1145
Status
Study Complete
Location
Austin & Repatriation Medical Centre
West Heidelberg, VIC, Australia, 3084
Status
Study Complete
Location
Hopital Neurologique Pierre Wertheimer
Lyon, Lyonnais, France, 69003
Status
Study Complete
Location
Walton Centre for Neurology & Neurosurgery
Liverpool, United Kingdom, L9 7LJ
Status
Study Complete
Location
Flinders Medical Centre
Bedford Park, SA, Australia, 5042
Status
Terminated/Withdrawn
Location
Mid-Atlantic Epilepsy and Sleep Center
Bethesda, MD, United States, 20817
Status
Study Complete
Location
District Antiepileptic Centre City Clinical Hospital # 71
Moscow, Russia, 121374
Status
Study Complete
Location
Institute of Neurology, Psychiatry and Narcology of AMS, Ukr
Kharkov, Ukraine, 61068
Status
Study Complete
Location
Clinic of Nervous Diseases of Sechenov's Moscow Med. Academy
Moscow, Russia, 119021
Status
Study Complete
Location
Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen
Erlangen, Germany, BY 91054
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2008-30-04
Actual study completion date
2008-30-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Click hereAccess to clinical trial data by researchers
Visit website