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
Study complete
Study complete
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:
Enrollment:
306
Primary completion date:
2008-31-01
Observational study model:
Not applicable
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
Showing 1 - 6 of 54 Results
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
Study complete
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
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