Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in Epilepsy

Condition(s) targeted: Epilepsies, Partial

Intervention: Retigabine (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Valeant Pharmaceuticals North America

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).

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 design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Reduction in total partial seizure frequency for four weeks from baseline to the double-blind period

Secondary outcome:

Proportion of responders defined as 50% or more reduction in total partial seizure frequency for four weeks from baseline to the double-blind period

Change in total partial seizure frequency per 4 weeks from baseline to the maintenance phase.

Proportion of patients experiencing a reduction in total partial seizure frequency in categories of 75-100%, 50-75%, 25-50%, or <25% from baseline to maintenance phase.

Proportion of patients experiencing an increase in total partial seizure frequency in categories of 0-25%, 25-50%, 50-100%, >100% from baseline to maintenance phase

Proportion of patients who are seizure free during the maintenance phase.

Proportion of seizure-free days during the maintenance phase for patients who entered the maintenance phase.

Incidence of new seizure types (e.g. status epilepticus, myoclonic, absence, secondary generalization) in patients without history of these seizure types

Change in the frequency of seizure types including those that may not be influenced by study drug (e.g., myoclonic, absence)

Clinical Global Impressions (CGI) assessments at the end of the maintenance phase

Patient Global Impressions (PGI) assessments at the end of the maintenance phase

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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

instituto Nacional de Neurologia y Neurocirugia, Mexico, DF, Mexico

North Alabama Neuroscience Research Associates, Huntsville, Alabama 35801, United States

Neurology Clinic, Northport, Alabama 35476, United States

University of Alabama -- Department of Neurology/Epilepsy Center, Birmingham, Alabama 35294, United States

Foothills Medical Center, Calgary, Alberta T2N 2T9, Canada

Glenrose Rehabilitation Center, Edmonton, Alberta T5G 0B7, Canada

Barrow Neurological Institute, Phoenix, Arizona 85013, United States

Clinical Trials Inc., Little rock, Arkansas 72205, United States

Hospital Universitario Prof Edgard Santos -- UFBA, Salvador, BA 40110-060, Brazil

Hospital General de Agudos "Dr. Teodoro Alvarez", Capital Federal, CBA C1406FWY, Argentina

Hospital General de Agudos "Dr. J.M. Ramos Mejia", Capital Federal, CBA C1221ADC, Argentina

Hospital Italiano de Buenos Aires, Capital Federal, CBA C1181ACH, Argentina

Hospital Privado Centro Medico de Cordoba, Cordoba, CRD X5016KEH, Argentina

Fundacion Lennox, Cordoba, CRD 5000, Argentina

Sanatorio del Salvador II, Cordoba, CRD 5000, Argentina

University of Southern California, Los Angeles, California 90033, United States

West Los Angeles VA Healthcare Center, Los Angeles, California 90073, United States

UCSD Thornton Hospital, La Jolla, California 92037, United States

Delta Waves, Colorado Springs, Colorado 80918, United States

University of Colorado Health Science Center, Denver, Colorado 80010, United States

Hospital de Psiquiatria San Fernando, IMSS, Mexico, DF 14050, Mexico

CIF BIOTEC, Medica Sur, Tlalpan, DF 14050, Mexico

Centro Medico, Mexico, DF 03229, Mexico

Instituto Nacional de Neurologia y Neurocirugia, La Fama, DF 42690, Mexico

University of Florida -- Shands Jacksonville, Jacksonville, Florida 32209, United States

Lovelace Scientific Resources, Sarasota, Florida 34233, United States

University of Miami, Miami, Florida 33136, United States

McFarland Clinic, Ames, Iowa 50010, United States

Antiguo Hospital Civil de Guadalajara, Guadalajara, Jalisco 44280, Mexico

University of Kentucky, Lexington, Kentucky 40536, United States

Mid-Atlantic Epilepsy and Sleep Center, Bethesda, Maryland 20817, United States

Henry Ford Hospital, Detroit, Michigan 48202, United States

Minnesota Epilepsy Group, P.A., St. Paul, Minnesota 55102, United States

The Comprehensive Epilepsy Care Center for Children and Adults, Chesterfield, Missouri 63017, United States

Beth Israel Medical Center, New York, New York 10003, United States

Health Sciences Centre, St. John's, Newfoundland and Labrador A1B 3V6, Canada

Asheville Neurology Specialists, Asheville, North Carolina 28801, United States

Hospital y Clinica OCA S.A. de C.V., Monterrey, Nuevo Leon 64000, Mexico

Medical University of Ohio at Toledo, Toledo, Ohio 43614, United States

Oregon Neurology PC, Tualatin, Oregon 97062, United States

Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, United States

Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

CHUM -- Hôpital Notre-Dame, Montréal, Quebec H2L 4M1, Canada

Hospital Central Dr. Ignacio Morones Prieto, San Luis Potosi, SLP 78250, Mexico

Hospital das Clinicas da Fac de Medicina de Sao Paulo, Sao Paulo, SP 05403-900, Brazil

Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia, Ribeirao Preto, SP 14048-900, Brazil

Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP, Sao Paulo, SP 04024 002, Brazil

Vanderbilt University Medical Center, Nashville, Tennessee 37212, United States

Meharry Medical College, Nashville, Tennessee 37208, United States

Neurological Clinic of Texas, Dallas, Texas 75230, United States

Memorial Hermann Hospital, Houston, Texas 77030, United States

Medical City Dallas Hospital, Dallas, Texas 75230, United States

Virginia Commonwealth University Medical Center, Richmond, Virginia 23298, United States

University of Virginia Comprehensive Epilepsy Program, Charlottesville, Virginia 22903, United States

Starting date: September 2005
Ending date: January 2008
Last updated: February 29, 2008