AzTrials
AzTrials

SeizuresPhase 3RESTORE1NCT00232596

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

A Phase 3 study testing Retigabine in people with Seizures, run by GlaxoSmithKline at 54 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Seizures
What is being tested?
Retigabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
306 participants
Where
54 sitesin 5 countries
Study dates
Sep 2005to Jan 2008
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Existing medical or psychiatric condition which could affect patient's health or compromise ability to participate in the study
  • Clinically significant abnormalities on physical exam, vital signs, ECG, or liver function tests
  • Impaired renal function (creatinine clearance less than 50 mL/minute)
  • Evidence of progressive central nervous disease, lesion, or encephalopathy
  • History of primary generalized seizures
  • History of clustering or flurries or status epilepticus within 12 months of study entry

Trial locations and contacts

54 sites in 5 countries.

54 sites in 5 countries

United States32 sites

  • McFarland Clinic

    Ames, Iowa, 50010

  • Asheville Neurology Specialists

    Asheville, North Carolina, 28801

  • Mid-Atlantic Epilepsy and Sleep Center

    Bethesda, Maryland, 20817

  • University of Alabama -- Department of Neurology/Epilepsy Center

    Birmingham, Alabama, 35294

  • University of Virginia Comprehensive Epilepsy Program

    Charlottesville, Virginia, 22903

  • The Comprehensive Epilepsy Care Center for Children and Adults

    Chesterfield, Missouri, 63017

  • Delta Waves

    Colorado Springs, Colorado, 80918

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Neurological Clinic of Texas

    Dallas, Texas, 75230

  • University of Colorado Health Science Center

    Denver, Colorado, 80010

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Memorial Hermann Hospital

    Houston, Texas, 77030

  • North Alabama Neuroscience Research Associates

    Huntsville, Alabama, 35801

  • University of Florida -- Shands Jacksonville

    Jacksonville, Florida, 32209

  • UCSD Thornton Hospital

    La Jolla, California, 92037

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Clinical Trials Inc.

    Little Rock, Arkansas, 72205

  • University of Southern California

    Los Angeles, California, 90033

  • West Los Angeles VA Healthcare Center

    Los Angeles, California, 90073

  • University of Miami

    Miami, Florida, 33136

  • Meharry Medical College

    Nashville, Tennessee, 37208

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

  • Beth Israel Medical Center

    New York, New York, 10003

  • Neurology Clinic

    Northport, Alabama, 35476

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Barrow Neurological Institute

    Phoenix, Arizona, 85013

  • Virginia Commonwealth University Medical Center

    Richmond, Virginia, 23298

  • Minnesota Epilepsy Group, P.A.

    Saint Paul, Minnesota, 55102

  • Lovelace Scientific Resources

    Sarasota, Florida, 34233

  • Medical University of Ohio at Toledo

    Toledo, Ohio, 43614

  • Oregon Neurology PC

    Tualatin, Oregon, 97062

Other trials in United States

Mexico8 sites

  • Antiguo Hospital Civil de Guadalajara

    Guadalajara, Jalisco, 44280

  • Instituto Nacional de Neurologia y Neurocirugia

    La Fama, Mexico City, 42690

  • Centro Medico

    Mexico City, Mexico City, 03229

  • Hospital de Psiquiatria San Fernando, IMSS

    Mexico City, Mexico City, 14050

  • instituto Nacional de Neurologia y Neurocirugia

    Mexico City

  • Hospital y Clinica OCA S.A. de C.V.

    Monterrey, Nuevo León, 64000

  • Hospital Central Dr. Ignacio Morones Prieto

    San Luis Potosí City, San Luis Potosí, 78250

  • CIF BIOTEC, Medica Sur

    Tlalpan, Mexico City, 14050

Other trials in Mexico

Argentina6 sites

  • Hospital Italiano de Buenos Aires

    Capital Federal, CBA, C1181ACH

  • Hospital General de Agudos "Dr. J.M. Ramos Mejia"

    Capital Federal, CBA, C1221ADC

  • Hospital General de Agudos "Dr. Teodoro Alvarez"

    Capital Federal, CBA, C1406FWY

  • Fundacion Lennox

    Córdoba, CRD, 5000

  • Sanatorio del Salvador II

    Córdoba, CRD, 5000

  • Hospital Privado Centro Medico de Cordoba

    Córdoba, CRD, X5016KEH

Other trials in Argentina

Brazil4 sites

  • Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia

    Ribeirão Preto, São Paulo, 14048-900

  • Hospital Universitario Prof Edgard Santos -- UFBA

    Salvador, Estado de Bahia, 40110-060

  • Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP

    São Paulo, São Paulo, 04024 002

  • Hospital das Clinicas da Fac de Medicina de Sao Paulo

    São Paulo, São Paulo, 05403-900

Other trials in Brazil

Canada4 sites

  • Foothills Medical Center

    Calgary, Alberta, T2N 2T9

  • Glenrose Rehabilitation Center

    Edmonton, Alberta, T5G 0B7

  • CHUM -- Hôpital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • Health Sciences Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

Other trials in Canada

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase 3 Study to Determine the Efficacy and Safety of Retigabine (1200 mg/Day) Used as Adjunctive Therapy in Refractory Epilepsy Patients With Partial-Onset Seizures

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).

Read the detailed description

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.

Conditions
Seizures
Being tested
Retigabine, Placebo
Keywords
Partial Seizures, Anticonvulsant, Complex Partial Seizures, Potassium Channels, Epilepsy
Medical subject headings
Seizures, Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RetigabineDrug

    Also called D-23129, GKE-841

    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

  • PlaceboDrug

    Oral tablet.

Study groups in NCT00232596
Study groupRoleWhat they receive
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo
RetigabineExperimentalNot described
Receives: Drug: Retigabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    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.

    Measured: Baseline (Week -7 through Week 0), Week 1 through Week 18

  2. Number of Participants Who Were Responders and Non-responders in the Maintenance Phase

    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.

    Measured: Week 7 through Week 18

Secondary outcomes (18)

  1. Number of Participants Who Were Responders and Non-responders in the DB Phase

    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.

    Measured: Week 1 through Week 18

  2. Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase

    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.

    Measured: Baseline (Week -7 through Week 0), Week 7 through Week 18

  3. 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

    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.

    Measured: Baseline (Week -7 through Week 0), Week 1 through Week 18

  4. 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

    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.

    Measured: Baseline (Week -7 through Week 0), Week 1 through Week 18

  5. Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase

    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).

    Measured: Baseline (Week -7 through Week 0), Week 7 through Week 18

  6. 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

    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.

    Measured: Baseline (Week -7 through Week 0), Week 7 through Week 18

  7. 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

    New seizure types included those seizures which were not reported by any participant at Baseline.

    Measured: Baseline (Week -7 through Week 0), Week 1 through Week 18

  8. Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)

    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.

    Measured: Week 1 through Week 18

  9. Number of Participants Who Were Seizure-free During the Maintenance Phase

    Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase.

    Measured: Week 7 through Week 18

  10. Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)

    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%.

    Measured: Week 1 through Week 18

  11. Percentage of Seizure-free Days During the Maintenance Phase

    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%.

    Measured: Week 7 through Week 18

  12. Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance 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.

    Measured: Week 18/end of treatment phase

  13. Patient Global Impression (PGI) Score at the End of the Maintenance 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.

    Measured: Week 18/end of treatment phase

  14. Quality of Life (QOL) Assessed by QOL in Epilepsy-Problems Questionnaire (QOLIE-31-P) at Baseline (Week 0) and 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.

    Measured: End of Baseline (Week 0), Weeks 6, 10, and 18

  15. Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)

    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.

    Measured: Week 1 through Week 24

  16. Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)

    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.

    Measured: Week 1 through Week 24

  17. Change From Baseline in Post-void Residual Urine Volume at Weeks 10 and 18 of the DB Treatment Phase

    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.

    Measured: Baseline (Week -7 through Week 0), Weeks 10 and 18

  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

    The number of participants with recorded weight gain of >=7% over their baseline weight was measured.

    Measured: Weeks 2, 4, 6 of Titration Phase and Weeks 7, 8, 10, 14, and 18 of Maintenance Phase

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2005 (estimated)
  2. Study startSep 2005
  3. Primary completionJan 2008
  4. Study completionJan 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
306 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00232596
Sponsor's protocol ID
VRX-RET-E22-301
Acronym
RESTORE1
Status last verified
Oct 2016
First submitted
30 Sep 2005
Last updated
8 Dec 2016
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Porter RJ, Burdette DE, Gil-Nagel A, Hall ST, White R, Shaikh S, DeRossett SE. Retigabine as adjunctive therapy in adults with partial-onset seizures: integrated analysis of three pivotal controlled trials. Epilepsy Res. 2012 Aug;101(1-2):103-12. doi: 10.1016/j.eplepsyres.2012.03.010. Epub 2012 Apr 16.

    PubMed 22512894

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Retigabine in people with Seizures, run by GlaxoSmithKline at 54 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States, Mexico, Argentina, Brazil, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Baseline (Week -7 through Week 0), Week 1 through Week 18). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00232596, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in