Clinical trial NCT00232596: Retigabine (Adjunctive Therapy) Efficacy and Safety Study for Partial Onset Refractory Seizures in Epilepsy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Seizures
Keywords: Partial Seizures
Anticonvulsant
Complex Partial Seizures
Potassium Channels
Epilepsy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Bausch Health Americas, Inc.
First posted: 2005-10-04
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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

Primary outcomes:
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)
timeFrame: Baseline (Week -7 through Week 0), Week 1 through Week 18
measure: Number of Participants Who Were Responders and Non-responders in the Maintenance Phase
timeFrame: Week 7 through Week 18
Secondary outcomes:
measure: Number of Participants Who Were Responders and Non-responders in the DB Phase
timeFrame: Week 1 through Week 18
measure: Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
timeFrame: Baseline (Week -7 through Week 0), Week 7 through Week 18
measure: 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
timeFrame: Baseline (Week -7 through Week 0), Week 1 through Week 18
measure: 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
timeFrame: Baseline (Week -7 through Week 0), Week 1 through Week 18
measure: Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
timeFrame: Baseline (Week -7 through Week 0), Week 7 through Week 18
measure: 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
timeFrame: Baseline (Week -7 through Week 0), Week 7 through Week 18
measure: 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
timeFrame: Baseline (Week -7 through Week 0), Week 1 through Week 18
measure: Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
timeFrame: Week 1 through Week 18
measure: Number of Participants Who Were Seizure-free During the Maintenance Phase
timeFrame: Week 7 through Week 18
measure: Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
timeFrame: Week 1 through Week 18
measure: Percentage of Seizure-free Days During the Maintenance Phase
timeFrame: Week 7 through Week 18
measure: Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
timeFrame: Week 18/end of treatment phase
measure: Patient Global Impression (PGI) Score at the End of the Maintenance Phase
timeFrame: Week 18/end of treatment phase
measure: Quality of Life (QOL) Assessed by QOL in Epilepsy-Problems Questionnaire (QOLIE-31-P) at Baseline (Week 0) and Weeks 6, 10, and 18
timeFrame: End of Baseline (Week 0), Weeks 6, 10, and 18
measure: Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
timeFrame: Week 1 through Week 24
measure: Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
timeFrame: Week 1 through Week 24
measure: Change From Baseline in Post-void Residual Urine Volume at Weeks 10 and 18 of the DB Treatment Phase
timeFrame: Baseline (Week -7 through Week 0), Weeks 10 and 18
measure: 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
timeFrame: Weeks 2, 4, 6 of Titration Phase and Weeks 7, 8, 10, 14, and 18 of Maintenance Phase
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama -- Department of Neurology/Epilepsy Center
state: Alabama
city: Huntsville
country: United States
facility: North Alabama Neuroscience Research Associates
state: Alabama
city: Northport
country: United States
facility: Neurology Clinic
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Little rock
country: United States
facility: Clinical Trials Inc.
state: Arkansas
city: La Jolla
country: United States
facility: UCSD Thornton Hospital
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: West Los Angeles VA Healthcare Center
state: California
city: Colorado Springs
country: United States
facility: Delta Waves
state: Colorado
city: Denver
country: United States
facility: University of Colorado Health Science Center
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida -- Shands Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Sarasota
country: United States
facility: Lovelace Scientific Resources
state: Florida
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: St. Paul
country: United States
facility: Minnesota Epilepsy Group, P.A.
state: Minnesota
city: Chesterfield
country: United States
facility: The Comprehensive Epilepsy Care Center for Children and Adults
state: Missouri
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: Asheville
country: United States
facility: Asheville Neurology Specialists
state: North Carolina
city: Toledo
country: United States
facility: Medical University of Ohio at Toledo
state: Ohio
city: Tualatin
country: United States
facility: Oregon Neurology PC
state: Oregon
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: Neurological Clinic of Texas
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Epilepsy Program
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Capital Federal
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: CBA
city: Capital Federal
country: Argentina
facility: Hospital General de Agudos "Dr. J.M. Ramos Mejia"
state: CBA
city: Capital Federal
country: Argentina
facility: Hospital General de Agudos "Dr. Teodoro Alvarez"
state: CBA
city: Cordoba
country: Argentina
facility: Fundacion Lennox
state: CRD
city: Cordoba
country: Argentina
facility: Sanatorio del Salvador II
state: CRD
city: Cordoba
country: Argentina
facility: Hospital Privado Centro Medico de Cordoba
state: CRD
city: Salvador
country: Brazil
facility: Hospital Universitario Prof Edgard Santos -- UFBA
state: BA
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Fac de Medicina de Sao Paulo
state: SP
city: Calgary
country: Canada
facility: Foothills Medical Center
state: Alberta
city: Edmonton
country: Canada
facility: Glenrose Rehabilitation Center
state: Alberta
city: St. John's
country: Canada
facility: Health Sciences Centre
state: Newfoundland and Labrador
city: Montréal
country: Canada
facility: CHUM -- Hôpital Notre-Dame
state: Quebec
city: La Fama
country: Mexico
facility: Instituto Nacional de Neurologia y Neurocirugia
state: DF
city: Mexico
country: Mexico
facility: Centro Medico
state: DF
city: Mexico
country: Mexico
facility: Hospital de Psiquiatria San Fernando, IMSS
state: DF
city: Tlalpan
country: Mexico
facility: CIF BIOTEC, Medica Sur
state: DF
city: Guadalajara
country: Mexico
facility: Antiguo Hospital Civil de Guadalajara
state: Jalisco
city: Monterrey
country: Mexico
facility: Hospital y Clinica OCA S.A. de C.V.
state: Nuevo Leon
city: San Luis Potosi
country: Mexico
facility: Hospital Central Dr. Ignacio Morones Prieto
state: SLP
city: Mexico, DF
country: Mexico
facility: instituto Nacional de Neurologia y Neurocirugia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.