Retigabine (Adjunctive Therapy) Efficacy and Safety Study for Partial Onset Refractory Seizures in Epilepsy (RESTORE1)
26 de octubre de 2016 actualizado por: GlaxoSmithKline
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
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).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
This Phase 3 study is being conducted in North America, Argentina, and Brazil 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).
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 total partial seizure frequency for four weeks from baseline to the double-blind period) will also be evaluated.
Tipo de estudio
Intervencionista
Inscripción (Actual)
306
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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CBA
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Capital Federal, CBA, Argentina, C1181ACH
- Hospital Italiano de Buenos Aires
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Capital Federal, CBA, Argentina, C1221ADC
- Hospital General de Agudos "Dr. J.M. Ramos Mejia"
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Capital Federal, CBA, Argentina, C1406FWY
- Hospital General de Agudos "Dr. Teodoro Alvarez"
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CRD
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Cordoba, CRD, Argentina, 5000
- Fundacion Lennox
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Cordoba, CRD, Argentina, 5000
- Sanatorio del Salvador II
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Cordoba, CRD, Argentina, X5016KEH
- Hospital Privado Centro Medico de Cordoba
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BA
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Salvador, BA, Brasil, 40110-060
- Hospital Universitario Prof Edgard Santos -- UFBA
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SP
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Ribeirao Preto, SP, Brasil, 14048-900
- Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia
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Sao Paulo, SP, Brasil, 04024 002
- Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP
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Sao Paulo, SP, Brasil, 05403-900
- Hospital das Clinicas da Fac de Medicina de Sao Paulo
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Alberta
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Calgary, Alberta, Canadá, T2N 2T9
- Foothills Medical Center
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Edmonton, Alberta, Canadá, T5G 0B7
- Glenrose Rehabilitation Center
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Newfoundland and Labrador
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St. John's, Newfoundland and Labrador, Canadá, A1B 3V6
- Health Sciences Centre
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Quebec
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Montréal, Quebec, Canadá, H2L 4M1
- CHUM -- Hôpital Notre-Dame
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294
- University of Alabama -- Department of Neurology/Epilepsy Center
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Huntsville, Alabama, Estados Unidos, 35801
- North Alabama Neuroscience Research Associates
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Northport, Alabama, Estados Unidos, 35476
- Neurology Clinic
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Arizona
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Phoenix, Arizona, Estados Unidos, 85013
- Barrow Neurological Institute
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Arkansas
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Little rock, Arkansas, Estados Unidos, 72205
- Clinical Trials Inc.
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California
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La Jolla, California, Estados Unidos, 92037
- UCSD Thornton Hospital
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Los Angeles, California, Estados Unidos, 90033
- University of Southern California
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Los Angeles, California, Estados Unidos, 90073
- West Los Angeles VA Healthcare Center
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Colorado
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Colorado Springs, Colorado, Estados Unidos, 80918
- Delta Waves
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Denver, Colorado, Estados Unidos, 80010
- University of Colorado Health Science Center
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Florida
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Jacksonville, Florida, Estados Unidos, 32209
- University of Florida -- Shands Jacksonville
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Miami, Florida, Estados Unidos, 33136
- University of Miami
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Sarasota, Florida, Estados Unidos, 34233
- Lovelace Scientific Resources
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Iowa
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Ames, Iowa, Estados Unidos, 50010
- McFarland Clinic
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Kentucky
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Lexington, Kentucky, Estados Unidos, 40536
- University of Kentucky
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Maryland
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Bethesda, Maryland, Estados Unidos, 20817
- Mid-Atlantic Epilepsy and Sleep Center
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Michigan
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Detroit, Michigan, Estados Unidos, 48202
- Henry Ford Hospital
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Minnesota
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St. Paul, Minnesota, Estados Unidos, 55102
- Minnesota Epilepsy Group, P.A.
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Missouri
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Chesterfield, Missouri, Estados Unidos, 63017
- The Comprehensive Epilepsy Care Center for Children and Adults
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New York
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New York, New York, Estados Unidos, 10003
- Beth Israel Medical Center
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North Carolina
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Asheville, North Carolina, Estados Unidos, 28801
- Asheville Neurology Specialists
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Ohio
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Toledo, Ohio, Estados Unidos, 43614
- Medical University of Ohio at Toledo
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Oregon
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Tualatin, Oregon, Estados Unidos, 97062
- Oregon Neurology PC
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Pennsylvania
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Hershey, Pennsylvania, Estados Unidos, 17033
- Milton S. Hershey Medical Center
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Hospital of the University of Pennsylvania
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37212
- Vanderbilt University Medical Center
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Nashville, Tennessee, Estados Unidos, 37208
- Meharry Medical College
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Texas
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Dallas, Texas, Estados Unidos, 75230
- Medical City Dallas Hospital
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Dallas, Texas, Estados Unidos, 75230
- Neurological Clinic of Texas
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Houston, Texas, Estados Unidos, 77030
- Memorial Hermann Hospital
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Virginia
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Charlottesville, Virginia, Estados Unidos, 22903
- University of Virginia Comprehensive Epilepsy Program
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Richmond, Virginia, Estados Unidos, 23298
- Virginia Commonwealth University Medical Center
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Mexico, DF, México
- Instituto Nacional de Neurologia y Neurocirugia
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DF
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La Fama, DF, México, 42690
- Instituto Nacional de Neurologia y Neurocirugia
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Mexico, DF, México, 03229
- Centro Medico
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Mexico, DF, México, 14050
- Hospital de Psiquiatria San Fernando, IMSS
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Tlalpan, DF, México, 14050
- CIF BIOTEC, Medica Sur
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Jalisco
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Guadalajara, Jalisco, México, 44280
- Antiguo Hospital Civil de Guadalajara
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Nuevo Leon
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Monterrey, Nuevo Leon, México, 64000
- Hospital y Clinica OCA S.A. de C.V.
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SLP
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San Luis Potosi, SLP, México, 78250
- Hospital Central Dr. Ignacio Morones Prieto
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 75 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador de placebos: Placebo
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Tableta oral.
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Experimental: Retigabine
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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 7, patients will enter a 12 week maintenance phase
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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)
Periodo de tiempo: Baseline (Week -7 through Week 0), Week 1 through Week 18
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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 values indicate a reduction in seizure frequency.
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Baseline (Week -7 through Week 0), Week 1 through Week 18
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Number of Participants Who Were Responders and Non-responders in the Maintenance Phase
Periodo de tiempo: Week 7 through Week 18
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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.
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Week 7 through Week 18
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of Participants Who Were Responders and Non-responders in the DB Phase
Periodo de tiempo: Week 1 through Week 18
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Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the DB Phase as compared to the Baseline period.
Participants without any post-baseline data were considered non-responders.
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Week 1 through Week 18
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Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
Periodo de tiempo: Baseline (Week -7 through Week 0), Week 7 through Week 18
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28-day total partial seizure frequency in the BL period = (No. of total partial seizures reported in the BL period divided by the No. of days of available total partial seizure data in the BL period) x 28 days.
28-day total partial seizure frequency in the Maintenance Phase = (No. of total partial seizures reported in the Maintenance Phase divided by the No. of days of available total partial seizure data in the same phase) x 28 days.
Percent change = (value in the Maintenance Phase minus value at BL divided by the BL value) x 100%.
Negative values indicate a reduction in seizure frequency.
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Baseline (Week -7 through Week 0), Week 7 through Week 18
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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
Periodo de tiempo: Baseline (Week -7 through Week 0), Week 1 through Week 18
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Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a reduction of 75-100%, 50-<75%, 25-<50%, or <25%, in addition to having no reduction.
This quartile cutting was specified in the study protocol.
Participants without any post-baseline data were included in the "No reduction" category.
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Baseline (Week -7 through Week 0), Week 1 through Week 18
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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
Periodo de tiempo: Baseline (Week -7 through Week 0), Week 1 through Week 18
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Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized in decile cutting, i.e., reduction categories of 90-100%, 80-<90%, 70-<80%, 60-<70%, 50-<60%, 40-<50%, 30-<40%, 20-<30%, 10-<20%, >0-<10%, and increase categories of 0-10%, >10-20%, >20-30%, >30% (FDA endpoint).
Participants without any post-baseline data were included in the 0-10% increase category.
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Baseline (Week -7 through Week 0), Week 1 through Week 18
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Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
Periodo de tiempo: Baseline (Week -7 through Week 0), Week 7 through Week 18
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Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a >75%, a 50-75%, or a <50% reduction, in addition to having no reduction (EMEA endpoint).
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Baseline (Week -7 through Week 0), Week 7 through Week 18
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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
Periodo de tiempo: Baseline (Week -7 through Week 0), Week 7 through Week 18
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Participants who experienced an exacerbation from Baseline in the 28-day total partial seizure frequency were categorized as having a 0-25% or a >25% increase (EMEA endpoint).
The number of participants experiencing a >0% reduction from Baseline in the 28-day total partial seizure frequency are also presented.
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Baseline (Week -7 through Week 0), Week 7 through Week 18
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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
Periodo de tiempo: Baseline (Week -7 through Week 0), Week 1 through Week 18
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New seizure types included those seizures which were not reported by any participant at Baseline.
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Baseline (Week -7 through Week 0), Week 1 through Week 18
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Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
Periodo de tiempo: Week 1 through Week 18
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Participants were considered to be seizure-free if they had not reported any seizures during the DB treatment period (Weeks 1-18).
For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6.
A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6.
Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18.
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Week 1 through Week 18
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Number of Participants Who Were Seizure-free During the Maintenance Phase
Periodo de tiempo: Week 7 through Week 18
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Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase.
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Week 7 through Week 18
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Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
Periodo de tiempo: Week 1 through Week 18
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A seizure-free day was a day without any seizures.
For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6.
A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6.
Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18.
The percentage of seizure-free days was calculated as the total number of days without seizures in the DB period divided by the number of days in DB period x 100%.
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Week 1 through Week 18
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Percentage of Seizure-free Days During the Maintenance Phase
Periodo de tiempo: Week 7 through Week 18
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A seizure-free day was a day without any seizures.
The percentage of seizure-free days was calculated as the total number of days without seizures in the DB period divided by the number of days in the DB period x 100%.
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Week 7 through Week 18
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Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
Periodo de tiempo: Week 18/end of treatment phase
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Clinical Global Impression of Improvement (CGI-I) is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the treatment.
Scores on the scale are rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
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Week 18/end of treatment phase
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Patient Global Impression (PGI) Score at the End of the Maintenance Phase
Periodo de tiempo: Week 18/end of treatment phase
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PGI is a participant-rated scale of improvement that was administered at the end of the Maintenance Phase in order to assess the participant's impression of his or her own improvement.
PGI assessments were scored using a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
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Week 18/end of treatment phase
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Quality of Life (QOL) Assessed by QOL in Epilepsy-Problems Questionnaire (QOLIE-31-P) at Baseline (Week 0) and Weeks 6, 10, and 18
Periodo de tiempo: End of Baseline (Week 0), Weeks 6, 10, and 18
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The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry, emotional well being, energy/fatigue, cognitive functioning, medication effects, social functioning, overall QOL.
Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state.
Precoded values are first converted to 0-100 point scores; higher converted scores always reflect better QOL.
The overall score is derived by weighting and then summing the 7 domain scores.
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End of Baseline (Week 0), Weeks 6, 10, and 18
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Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Periodo de tiempo: Week 1 through Week 24
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Clinically important changes in laboratory values were to be reported as an adverse event if they met one of the following criteria: (1) intervention required; (2) change in dose of study drug required; (3) other treatment/therapy required; (4) association with other diagnoses.
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Week 1 through Week 24
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Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Periodo de tiempo: Week 1 through Week 24
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A summary of the adverse events classified as renal or urinary disorders and in which at least 2% (rounded to an integer) of participants in any treatment arm reported during the study is presented.
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Week 1 through Week 24
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Change From Baseline in Post-void Residual Urine Volume at Weeks 10 and 18 of the DB Treatment Phase
Periodo de tiempo: Baseline (Week -7 through Week 0), Weeks 10 and 18
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Post-void residual (PVR) urine refers to the amount of urine remaining in the bladder after normal urination.
To investigate the possible effects of retigabine on bladder function, all participants underwent post-void residual bladder ultrasound at Baseline and during the Maintenance Phase.
The PVR bladder ultrasound was performed by a urologist, a qualified ultrasound technician, or a qualified study nurse who was certified to do PVR bladder ultrasound.
Change from Baseline in PVR residual volume was calculated as the values at Week 10 and Week 18 minus the value at Baseline.
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Baseline (Week -7 through Week 0), Weeks 10 and 18
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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
Periodo de tiempo: Weeks 2, 4, 6 of Titration Phase and Weeks 7, 8, 10, 14, and 18 of Maintenance Phase
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The number of participants with recorded weight gain of >=7% over their baseline weight was measured.
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Weeks 2, 4, 6 of Titration Phase and Weeks 7, 8, 10, 14, and 18 of Maintenance Phase
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de septiembre de 2005
Finalización primaria (Actual)
1 de enero de 2008
Finalización del estudio (Actual)
1 de enero de 2008
Fechas de registro del estudio
Enviado por primera vez
30 de septiembre de 2005
Primero enviado que cumplió con los criterios de control de calidad
30 de septiembre de 2005
Publicado por primera vez (Estimar)
4 de octubre de 2005
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
8 de diciembre de 2016
Última actualización enviada que cumplió con los criterios de control de calidad
26 de octubre de 2016
Última verificación
1 de octubre de 2016
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- VRX-RET-E22-301
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Datos del estudio/Documentos
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Informe de estudio clínico
Identificador de información: VRX-RET-E22-301Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Protocolo de estudio
Identificador de información: VRX-RET-E22-301Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Formulario de informe de caso anotado
Identificador de información: VRX-RET-E22-301Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Especificación del conjunto de datos
Identificador de información: VRX-RET-E22-301Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Conjunto de datos de participantes individuales
Identificador de información: VRX-RET-E22-301Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Plan de Análisis Estadístico
Identificador de información: VRX-RET-E22-301Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Formulario de consentimiento informado
Identificador de información: VRX-RET-E22-301Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .