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

26 octobre 2016 mis à jour par: 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).

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

306

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur placebo: Placebo
Médicament: Placebo
Comprimé oral.
Expérimental: Retigabine
Médicament: 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
Autres noms:
  • GKE-841
  • D-23129

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
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)
Délai: 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
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of Participants Who Were Responders and Non-responders in the DB Phase
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

GlaxoSmithKline

Collaborateurs

Bausch Health Americas, Inc.

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 septembre 2005

Achèvement primaire (Réel)

1 janvier 2008

Achèvement de l'étude (Réel)

1 janvier 2008

Dates d'inscription aux études

Première soumission

30 septembre 2005

Première soumission répondant aux critères de contrôle qualité

30 septembre 2005

Première publication (Estimation)

4 octobre 2005

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

8 décembre 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

26 octobre 2016

Dernière vérification

1 octobre 2016

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • VRX-RET-E22-301

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

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

Données/documents d'étude

  1. Rapport d'étude clinique
    Identifiant des informations: VRX-RET-E22-301
    Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
  2. Protocole d'étude
    Identifiant des informations: VRX-RET-E22-301
    Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
  3. Formulaire de rapport de cas annoté
    Identifiant des informations: VRX-RET-E22-301
    Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
  4. Spécification du jeu de données
    Identifiant des informations: VRX-RET-E22-301
    Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
  5. Ensemble de données de participant individuel
    Identifiant des informations: VRX-RET-E22-301
    Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
  6. Plan d'analyse statistique
    Identifiant des informations: VRX-RET-E22-301
    Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register
  7. Formulaire de consentement éclairé
    Identifiant des informations: VRX-RET-E22-301
    Commentaires d'informations: For additional information about this study please refer to the GSK Clinical Study Register

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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