Last updated: 11/07/2018 19:58:04
Retigabine (adjunctive therapy) Efficacy and Safety Study for Partial Onset Refractory Seizures in EpilepsyRESTORE1
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase 3 Study to Determine the Efficacy and Safety of Retigabine (1200 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 1200 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), Week 1 through Week 18
Number of participants who were responders and non-responders in the Maintenance Phase
Timeframe: Week 7 through Week 18
Secondary outcomes:
Number of participants who were responders and non-responders in the DB Phase
Timeframe: Week 1 through Week 18
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 7 through Week 18
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 18
Number of participants with a reduction in the 28-day total partial seizure frequency from Baseline to the end of 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 18
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 7 through Week 18
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 7 through Week 18
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 18
Number of participants who were seizure-free during the DB Phase (Titration and Maintenance Phases)
Timeframe: Week 1 through Week 18
Number of participants who were seizure-free during the Maintenance Phase
Timeframe: Week 7 through Week 18
Percentage of seizure-free days during the DB Phase (Titration and Maintenance Phases)
Timeframe: Week 1 through Week 18
Percentage of seizure-free days during the Maintenance Phase
Timeframe: Week 7 through Week 18
Clinical Global Impression-Improvement (CGI-I) score at the end of the Maintenance Phase
Timeframe: Week 18/end of treatment phase
Patient Global Impression (PGI) score at the end of the Maintenance Phase
Timeframe: Week 18/end of treatment phase
Quality of life (QOL) assessed by QOL in Epilepsy-Problems Questionnaire (QOLIE-31-P) at Baseline (Week 0) and Weeks 6, 10, and 18
Timeframe: End of Baseline (Week 0), Weeks 6, 10, and 18
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 24
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 24
Change from Baseline in post-void residual urine volume at Weeks 10 and 18 of the DB treatment phase
Timeframe: Baseline (Week -7 through Week 0), Weeks 10 and 18
Number of participants with a >=7% increase in body weight during Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Timeframe: Weeks 2, 4, 6 of Titration Phase and Weeks 7, 8, 10, 14, and 18 of Maintenance Phase
Interventions:
Drug: Retigabine
Drug: Placebo
Enrollment:
306
Observational study model:
Not applicable
Primary completion date:
2008-31-01
Time perspective:
Not applicable
Clinical publications:
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.
JA French, MD; BW Abou-Khalil MD; RF Leroy, MD; EMT Yacubian, MD; P Shin MS,5 S Hall PhD, H Mansbach MD, and V Nohria MD7 on behalf of the RESTORE 1/Study 301 Investigators. Retigabine Efficacy and Safety Trial for Partial Onset Epilepsy (RESTORE 1): Double-blind, randomized, placebo-controlled trial of retigabine 1200 mg/day as adjunctive therapy in adults with partial-onset seizures. Neurology.
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;
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.
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)
September 2005 to January 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
Medical University of Ohio at Toledo
Toledo, Ohio, United States, 43614
Status
Recruiting
Location
Antiguo Hospital Civil de Guadalajara
Guadalajara, Jalisco, Mexico, 44280
Status
Recruiting
Location
Meharry Medical College
Nashville, TN, United States, 37208
Status
Recruitment Complete
Location
Virginia Commonwealth University Medical Center
Richmond, Virginia, United States, 23298
Status
Recruiting
Location
Minnesota Epilepsy Group, P.A.
St. Paul, Minnesota, United States, 55102
Status
Recruiting
Location
The Comprehensive Epilepsy Care Center for Children and Adults
Chesterfield, Missouri, United States, 63017
Status
Recruitment Complete
Location
University of Southern California
Los Angeles, California, United States, 90033
Status
Recruitment Complete
Location
Hospital de Psiquiatria San Fernando, IMSS
Mexico, DF, Mexico, 14050
Status
Recruiting
Location
Beth Israel Medical Center
New York, New York, United States, 10003
Status
Recruiting
Location
Hospital Central Dr. Ignacio Morones Prieto
San Luis Potosi, SLP, Mexico, 78250
Status
Will Be Recruiting
Location
Hospital of the University of Pennsylvania
Philadelphia, PA, United States, 19104
Status
Recruitment Complete
Location
Instituto Nacional de Neurologia y Neurocirugia
La Fama, DF, Mexico, 42690
Status
Recruiting
Location
North Alabama Neuroscience Research Associates
Huntsville, Alabama, United States, 35801
Status
Recruiting
Location
Asheville Neurology Specialists
Asheville, North Carolina, United States, 28801
Status
Recruitment Complete
Location
Hospital Universitario Prof Edgard Santos -- UFBA
Salvador, BA, Brazil, 40110-060
Status
Recruiting
Location
Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland, United States, 20817
Status
Recruiting
Location
Hospital Privado Centro Medico de Cordoba
Cordoba, CRD, Argentina, X5016KEH
Status
Recruiting
Location
University of Virginia Comprehensive Epilepsy Program
Charlottesville, Virginia, United States, 22903
Status
Recruiting
Location
Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Status
Recruitment Complete
Location
Hospital y Clinica OCA S.A. de C.V.
Monterrey, Nuevo Leon, Mexico, 64000
Status
Recruiting
Location
West Los Angeles VA Healthcare Center
Los Angeles, California, United States, 90073
Status
Recruitment Complete
Location
Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP
Sao Paulo, SP, Brazil, 04024 002
Status
Recruiting
Location
Hospital General de Agudos "Dr. Teodoro Alvarez"
Capital Federal, CBA, Argentina, C1406FWY
Status
Recruiting
Location
Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia
Ribeirao Preto, SP, Brazil, 14048-900
Status
Recruiting
Location
Lovelace Scientific Resources
Sarasota, Florida, United States, 34233
Status
Recruiting
Location
Barrow Neurological Institute
Phoenix, Arizona, United States, 85013
Status
Recruitment Complete
Location
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
Status
Recruitment Complete
Location
Hospital das Clinicas da Fac de Medicina de Sao Paulo
Sao Paulo, SP, Brazil, 05403-900
Status
Recruiting
Location
University of Florida -- Shands Jacksonville
Jacksonville, Florida, United States, 32209
Status
Recruiting
Location
instituto Nacional de Neurologia y Neurocirugia
Mexico, DF, Mexico
Status
Recruitment Complete
Location
Clinical Trials Inc.
Little rock, Arkansas, United States, 72205
Status
Recruitment Complete
Location
University of Colorado Health Science Center
Denver, CO, United States, 80010
Status
Recruitment Complete
Location
Hospital General de Agudos "Dr. J.M. Ramos Mejia"
Capital Federal, CBA, Argentina, C1221ADC
Status
Recruiting
Location
University of Alabama -- Department of Neurology/Epilepsy Center
Birmingham, Alabama, United States, 35294
Status
Recruiting
Location
Medical City Dallas Hospital
Dallas, TX, United States, 75230
Status
Recruitment Complete
Location
Hospital Italiano de Buenos Aires
Capital Federal, CBA, Argentina, C1181ACH
Status
Recruiting
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
2008-31-01
Actual study completion date
2008-31-01
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