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Retigabine (Adjunctive Therapy) Efficacy and Safety Study for Partial Onset Refractory Seizures in Epilepsy (RESTORE1)

26 ottobre 2016 aggiornato da: 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).

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Effettivo)

306

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Argentina
    • CBA
      • Capital Federal, CBA, Argentina, C1181ACH
        • Hospital Italiano de Buenos Aires
      • Capital Federal, CBA, Argentina, C1221ADC
        • Hospital General de Agudos "Dr. J.M. Ramos Mejia"
      • Capital Federal, CBA, Argentina, C1406FWY
        • Hospital General de Agudos "Dr. Teodoro Alvarez"
    • CRD
      • Cordoba, CRD, Argentina, 5000
        • Fundacion Lennox
      • Cordoba, CRD, Argentina, 5000
        • Sanatorio del Salvador II
      • Cordoba, CRD, Argentina, X5016KEH
        • Hospital Privado Centro Medico de Cordoba
  • Brasile
    • BA
      • Salvador, BA, Brasile, 40110-060
        • Hospital Universitario Prof Edgard Santos -- UFBA
    • SP
      • Ribeirao Preto, SP, Brasile, 14048-900
        • Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia
      • Sao Paulo, SP, Brasile, 04024 002
        • Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP
      • Sao Paulo, SP, Brasile, 05403-900
        • Hospital das Clinicas da Fac de Medicina de Sao Paulo
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Foothills Medical Center
      • Edmonton, Alberta, Canada, T5G 0B7
        • Glenrose Rehabilitation Center
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Health Sciences Centre
    • Quebec
      • Montréal, Quebec, Canada, H2L 4M1
        • CHUM -- Hôpital Notre-Dame
  • Messico
      • Mexico, DF, Messico
        • Instituto Nacional de Neurologia y Neurocirugia
    • DF
      • La Fama, DF, Messico, 42690
        • Instituto Nacional de Neurologia y Neurocirugia
      • Mexico, DF, Messico, 03229
        • Centro Medico
      • Mexico, DF, Messico, 14050
        • Hospital de Psiquiatria San Fernando, IMSS
      • Tlalpan, DF, Messico, 14050
        • CIF BIOTEC, Medica Sur
    • Jalisco
      • Guadalajara, Jalisco, Messico, 44280
        • Antiguo Hospital Civil de Guadalajara
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Messico, 64000
        • Hospital y Clinica OCA S.A. de C.V.
    • SLP
      • San Luis Potosi, SLP, Messico, 78250
        • Hospital Central Dr. Ignacio Morones Prieto
  • Stati Uniti
    • Alabama
      • Birmingham, Alabama, Stati Uniti, 35294
        • University of Alabama -- Department of Neurology/Epilepsy Center
      • Huntsville, Alabama, Stati Uniti, 35801
        • North Alabama Neuroscience Research Associates
      • Northport, Alabama, Stati Uniti, 35476
        • Neurology Clinic
    • Arizona
      • Phoenix, Arizona, Stati Uniti, 85013
        • Barrow Neurological Institute
    • Arkansas
      • Little rock, Arkansas, Stati Uniti, 72205
        • Clinical Trials Inc.
    • California
      • La Jolla, California, Stati Uniti, 92037
        • UCSD Thornton Hospital
      • Los Angeles, California, Stati Uniti, 90033
        • University of Southern California
      • Los Angeles, California, Stati Uniti, 90073
        • West Los Angeles VA Healthcare Center
    • Colorado
      • Colorado Springs, Colorado, Stati Uniti, 80918
        • Delta Waves
      • Denver, Colorado, Stati Uniti, 80010
        • University of Colorado Health Science Center
    • Florida
      • Jacksonville, Florida, Stati Uniti, 32209
        • University of Florida -- Shands Jacksonville
      • Miami, Florida, Stati Uniti, 33136
        • University of Miami
      • Sarasota, Florida, Stati Uniti, 34233
        • Lovelace Scientific Resources
    • Iowa
      • Ames, Iowa, Stati Uniti, 50010
        • McFarland Clinic
    • Kentucky
      • Lexington, Kentucky, Stati Uniti, 40536
        • University of Kentucky
    • Maryland
      • Bethesda, Maryland, Stati Uniti, 20817
        • Mid-Atlantic Epilepsy and Sleep Center
    • Michigan
      • Detroit, Michigan, Stati Uniti, 48202
        • Henry Ford Hospital
    • Minnesota
      • St. Paul, Minnesota, Stati Uniti, 55102
        • Minnesota Epilepsy Group, P.A.
    • Missouri
      • Chesterfield, Missouri, Stati Uniti, 63017
        • The Comprehensive Epilepsy Care Center for Children and Adults
    • New York
      • New York, New York, Stati Uniti, 10003
        • Beth Israel Medical Center
    • North Carolina
      • Asheville, North Carolina, Stati Uniti, 28801
        • Asheville Neurology Specialists
    • Ohio
      • Toledo, Ohio, Stati Uniti, 43614
        • Medical University of Ohio at Toledo
    • Oregon
      • Tualatin, Oregon, Stati Uniti, 97062
        • Oregon Neurology PC
    • Pennsylvania
      • Hershey, Pennsylvania, Stati Uniti, 17033
        • Milton S. Hershey Medical Center
      • Philadelphia, Pennsylvania, Stati Uniti, 19104
        • Hospital of the University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37212
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, Stati Uniti, 37208
        • Meharry Medical College
    • Texas
      • Dallas, Texas, Stati Uniti, 75230
        • Medical City Dallas Hospital
      • Dallas, Texas, Stati Uniti, 75230
        • Neurological Clinic of Texas
      • Houston, Texas, Stati Uniti, 77030
        • Memorial Hermann Hospital
    • Virginia
      • Charlottesville, Virginia, Stati Uniti, 22903
        • University of Virginia Comprehensive Epilepsy Program
      • Richmond, Virginia, Stati Uniti, 23298
        • Virginia Commonwealth University Medical Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore placebo: Placebo
Droga: Placebo
Compressa orale.
Sperimentale: Retigabine
Droga: Retigabine
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
Altri nomi:
  • GKE-841
  • D-23129

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
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)
Lasso di tempo: Baseline (Week -7 through Week 0), Week 1 through Week 18
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.
Baseline (Week -7 through Week 0), Week 1 through Week 18
Number of Participants Who Were Responders and Non-responders in the Maintenance Phase
Lasso di tempo: Week 7 through Week 18
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.
Week 7 through Week 18

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants Who Were Responders and Non-responders in the DB Phase
Lasso di tempo: Week 1 through Week 18
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.
Week 1 through Week 18
Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
Lasso di tempo: Baseline (Week -7 through Week 0), Week 7 through Week 18
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.
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
Lasso di tempo: Baseline (Week -7 through Week 0), Week 1 through Week 18
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.
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
Lasso di tempo: Baseline (Week -7 through Week 0), Week 1 through Week 18
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.
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
Lasso di tempo: Baseline (Week -7 through Week 0), Week 7 through Week 18
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).
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
Lasso di tempo: Baseline (Week -7 through Week 0), Week 7 through Week 18
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.
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
Lasso di tempo: Baseline (Week -7 through Week 0), Week 1 through Week 18
New seizure types included those seizures which were not reported by any participant at Baseline.
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)
Lasso di tempo: Week 1 through Week 18
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.
Week 1 through Week 18
Number of Participants Who Were Seizure-free During the Maintenance Phase
Lasso di tempo: Week 7 through Week 18
Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase.
Week 7 through Week 18
Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
Lasso di tempo: Week 1 through Week 18
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%.
Week 1 through Week 18
Percentage of Seizure-free Days During the Maintenance Phase
Lasso di tempo: Week 7 through Week 18
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%.
Week 7 through Week 18
Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
Lasso di tempo: Week 18/end of treatment phase
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.
Week 18/end of treatment phase
Patient Global Impression (PGI) Score at the End of the Maintenance Phase
Lasso di tempo: Week 18/end of treatment phase
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.
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
Lasso di tempo: End of Baseline (Week 0), Weeks 6, 10, and 18
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.
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)
Lasso di tempo: Week 1 through Week 24
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.
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)
Lasso di tempo: Week 1 through Week 24
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.
Week 1 through Week 24
Change From Baseline in Post-void Residual Urine Volume at Weeks 10 and 18 of the DB Treatment Phase
Lasso di tempo: Baseline (Week -7 through Week 0), Weeks 10 and 18
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.
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
Lasso di tempo: Weeks 2, 4, 6 of Titration Phase and Weeks 7, 8, 10, 14, and 18 of Maintenance Phase
The number of participants with recorded weight gain of >=7% over their baseline weight was measured.
Weeks 2, 4, 6 of Titration Phase and Weeks 7, 8, 10, 14, and 18 of Maintenance Phase

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

GlaxoSmithKline

Collaboratori

Bausch Health Americas, Inc.

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 settembre 2005

Completamento primario (Effettivo)

1 gennaio 2008

Completamento dello studio (Effettivo)

1 gennaio 2008

Date di iscrizione allo studio

Primo inviato

30 settembre 2005

Primo inviato che soddisfa i criteri di controllo qualità

30 settembre 2005

Primo Inserito (Stima)

4 ottobre 2005

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

8 dicembre 2016

Ultimo aggiornamento inviato che soddisfa i criteri QC

26 ottobre 2016

Ultimo verificato

1 ottobre 2016

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • VRX-RET-E22-301

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Dati/documenti di studio

  1. Rapporto di studio clinico
    Identificatore informazioni: VRX-RET-E22-301
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  2. Protocollo di studio
    Identificatore informazioni: VRX-RET-E22-301
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  3. Modulo di segnalazione del caso annotato
    Identificatore informazioni: VRX-RET-E22-301
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  4. Specifica del set di dati
    Identificatore informazioni: VRX-RET-E22-301
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  5. Set di dati del singolo partecipante
    Identificatore informazioni: VRX-RET-E22-301
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  6. Piano di analisi statistica
    Identificatore informazioni: VRX-RET-E22-301
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  7. Modulo di consenso informato
    Identificatore informazioni: VRX-RET-E22-301
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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