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

26. oktober 2016 oppdatert av: 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).

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

306

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 75 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Placebo komparator: Placebo
Legemiddel: Placebo
Oral tablett.
Eksperimentell: Retigabine
Legemiddel: 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
Andre navn:
  • GKE-841
  • D-23129

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
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)
Tidsramme: 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
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Participants Who Were Responders and Non-responders in the DB Phase
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

GlaxoSmithKline

Samarbeidspartnere

Bausch Health Americas, Inc.

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. september 2005

Primær fullføring (Faktiske)

1. januar 2008

Studiet fullført (Faktiske)

1. januar 2008

Datoer for studieregistrering

Først innsendt

30. september 2005

Først innsendt som oppfylte QC-kriteriene

30. september 2005

Først lagt ut (Anslag)

4. oktober 2005

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

8. desember 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

26. oktober 2016

Sist bekreftet

1. oktober 2016

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • VRX-RET-E22-301

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

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

Studiedata/dokumenter

  1. Klinisk studierapport
    Informasjonsidentifikator: VRX-RET-E22-301
    Informasjonskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  2. Studieprotokoll
    Informasjonsidentifikator: VRX-RET-E22-301
    Informasjonskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  3. Annotert saksrapportskjema
    Informasjonsidentifikator: VRX-RET-E22-301
    Informasjonskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  4. Datasettspesifikasjon
    Informasjonsidentifikator: VRX-RET-E22-301
    Informasjonskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  5. Datasett for individuell deltaker
    Informasjonsidentifikator: VRX-RET-E22-301
    Informasjonskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  6. Statistisk analyseplan
    Informasjonsidentifikator: VRX-RET-E22-301
    Informasjonskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  7. Skjema for informert samtykke
    Informasjonsidentifikator: VRX-RET-E22-301
    Informasjonskommentarer: For additional information about this study please refer to the GSK Clinical Study Register

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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