Clinical trial NCT00334958: Rufinamide Given as Adjunctive Therapy in Participants With Refractory Partial Seizures
Official title: A Double-Blind, Placebo-Controlled, Parallel-Group Study of Rufinamide Given as Adjunctive Therapy in Patients With Refractory Partial Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2006-06-08
Enrollment: 356
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the effect of rufinamide on total partial seizure frequency in adolescent and adult participants (12 to 80 years, inclusive) with refractory partial onset seizures maintained on a maximum of 3 stable antiepileptic drugs (AEDs).


Eligibility criteria: INCLUSION CRITERIA

1. Male and female patients between 12 and 80 years of age, inclusive.
2. Diagnosis of epilepsy with partial-onset seizures with or without secondarily generalized seizures according with the International League Against Epilepsy Classification of Epileptic Seizures (1981). Diagnosis should have been established by clinical history, electroencephalogram (EEG) and computed tomography/magnetic resonance imaging (CT/MRI) of the brain performed within the last 10 years and consistent with localization-related epilepsy.
3. Non-controlled partial seizures despite having been treated with at least two different antiepileptic drugs (given concurrently or sequentially) for at least two years.
4. Patient willing to participate and written consent signed by patient or legal guardian prior to entering the study or undergoing any study procedures. If the written consent is provided by a legal guardian because the patient is unable to do so, assent of the patient must also be obtained.
5. Reliability and willingness of patients to make themselves available for the study period, and ability to record seizures and report adverse events themselves or have a caregiver who can record seizures and report adverse events.
6. Female patients of non-childbearing potential by reason of surgery, radiation, or menopause (at least one year post onset); or of childbearing potential using two approved methods of contraception (such as an intrauterine device \[IUD\], implant, oral contraceptive, or barrier method plus spermicide). Use of a low-dose estrogen oral contraceptive ("minipill") alone will not be permitted. Female patients of childbearing potential must have a confirmed negative serum pregnancy test at screening and a negative urine pregnancy test prior to randomization, and agree to continue to use two approved methods of contraception through the follow-up visit (Visit 8) or for 30 days after their final dose of study medication, whichever is longer.
7. At least six seizures during the prospective Baseline Phase (56 days) with no 21-day seizure-free periods. Simple partial seizures without motor signs will not be included in determining this criterion.
8. Current treatment with a maximum of three approved antiepileptic drugs, and no evidence of non-compliance with ongoing AED therapy.
9. Stable dose(s) of the same AED(s) for one month prior to screening.
10. If using a vagal nerve stimulator, it must have been implanted for at least six months prior to randomization. Stimulator parameters may not be changed for at least one month prior to screening or thereafter during the study. Magnet use will be allowed, but must be documented throughout the study. A vagal nerve stimulator will not be counted as an AED for the purpose of inclusion into the trial.

EXCLUSION CRITERIA:

1. Participation in a study involving administration of an investigational compound within one month of Visit 1 (Screening), or within five half-lives of the previous investigational compound, whichever is longer; or any prior exposure to rufinamide.
2. Presence of non-motor simple partial seizures only.
3. Presence of generalized epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome.
4. History of status epilepticus in the past year or seizure clusters where individual seizures cannot be counted.
5. Evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, hepatic, hematologic or renal disease, etc.) that in the opinion of the Investigator could affect the patient's safety or trial conduct.
6. Clinically significant ECG abnormality.
7. Patients with a diagnosis of major active psychiatric disease will be excluded from the study. However, those patients who are only taking a stable dose of either a selective serotonin reuptake inhibitor (SSRI) antidepressant drug or a serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant drug for a diagnosed depressive disorder can be included as long as they have been on the SSRI or SNRI for a period of two months or longer before randomization. Other antidepressant medications will not be allowed.
8. Progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
9. Occurrence of psychogenic seizures in the previous year.
10. History of drug abuse and/or positive finding on urinary drug screening, other than prescribed medication
11. History of alcohol abuse in the past two years.
12. History of suicide attempt within the previous 10 years.
13. Multiple drug allergies (dermatological, hematological or organ toxicity) or more than one severe drug reaction(s).
14. Concomitant use of felbamate or use of felbamate within two months prior to Visit 1.
15. Frequent need of rescue benzodiazepines (more than once a month).
16. Patients with a known hypersensitivity to rufinamide, triazole derivatives, or to any excipients used in the formulation.
17. Concomitant use of vigabatrin. Patients who took vigabatrin in the past must be off vigabatrin for at least five months prior to Visit 1 and must not have evidence of a clinically significant abnormality in a visual perimetry test.
18. All Patients with a diagnosis of Congenital Short QT Syndrome. Patients with a family history of Congenital Short QT Syndrome may be excluded on the basis of the Investigator's clinical judgment.

Primary outcomes:
measure: Percentage Change in Total Partial Seizure Frequency Per 28 Days During Maintenance Phase Relative to the Baseline Phase
timeFrame: Baseline, Days 13 to 96
Secondary outcomes:
measure: Percentage of Participants With 50% or Greater Reduction in Total Partial Seizure Frequency Per 28 Days During the Maintenance Phase Relative to the Baseline Phase
timeFrame: Baseline, Days 13 to 96
measure: Log10 Transformed Total Partial Seizure Frequency Per 28 Days During the Baseline Phase and Maintenance Phase
timeFrame: Days 13 to 96
measure: Reduction From Baseline in Total Partial Seizure Frequency Rate (RRATIO) During Maintenance Phase
timeFrame: Baseline, Days 13 to 96
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Medical Center
state: Alabama
city: Northport
country: United States
facility: Neurology Clinic PC
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Epilepsy and Neurology
state: Arizona
city: Tucson
country: United States
facility: University of Arizona, Dept. of Neurology
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials, Inc
state: Arkansas
city: Fresno
country: United States
facility: Neuro-Pain Medical Center, Inc.
state: California
city: Oceanside
country: United States
facility: Neurology Center
state: California
city: San Francisco
country: United States
facility: California Pacific Epilepsy
state: California
city: Washington
country: United States
facility: Georgetown University Hospital, Dept. of Neurology
state: District of Columbia
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Gainesville
country: United States
facility: University of Florida, Dept. of Neurology
state: Florida
city: Jacksonville
country: United States
facility: University of Florida, The Neuroscience Institute at Shands
state: Florida
city: Loxahatchee Groves
country: United States
facility: Pediatric Neurologists of Palm Beach
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Pediatric Neurology - PA
state: Florida
city: Panama City
country: United States
facility: Bay Medical Center
state: Florida
city: Tampa
country: United States
facility: University of Southern Florida, Dept. of Neurology
state: Florida
city: Atlanta
country: United States
facility: Child Neurology Associates, PC
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia, Dept. of Neurology
state: Georgia
city: Canton
country: United States
facility: Medical Associates of North Georgia
state: Georgia
city: Honolulu
country: United States
facility: The Queen's Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Children's Memorial Hospital, Northwest University
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Hope Children's Hospital
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Children's Hospital
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University Neurology and Pharmacology
state: Illinois
city: Ames
country: United States
facility: Mcfarland Clinic
state: Iowa
city: Wichita
country: United States
facility: Via Christi Comprehensive Epilepsy Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, Dept. of Neurology
state: Kentucky
city: Baltimore
country: United States
facility: John Hopkins Hospital, Dept. of Neurology
state: Maryland
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center, Dept. of Neurology
state: Massachusetts
city: Hopedale
country: United States
facility: University of Massachusetts, Neurology Associates
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, Dept. of Neurology
state: Minnesota
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group, PC
state: Minnesota
city: Hattiesburg
country: United States
facility: Ronald Schwartz, M.D.
state: Mississippi
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Chesterfield
country: United States
facility: The Comprehensive Epilepsy Care Center for Children and Adults
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Springfield
country: United States
facility: Saint John's Medical Research
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Medical School Neuroscience Center
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore Medical Center, Albert Einstein College of Medicine
state: New York
city: Lawrence
country: United States
facility: Five Towns Neuroscience Research
state: New York
city: New York
country: United States
facility: New York University Medical Centre, Comprehensive Epilepsy Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center, Comprehensive Epilepsy Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Asheville
country: United States
facility: Asheville Neurology Specialists, PA
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill, Dept. of Neurology
state: North Carolina
city: Durham
country: United States
facility: Duke Health Center at Morreene Road
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation, Dept. of Neurology
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio at Toledo, Dept. of Neurology
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Altoona
country: United States
facility: Blair Medical Associates, Inc.
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of The University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania, Dept. of Neurology
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh - Dept of Pediatrics
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Germantown
country: United States
facility: Mid-South Physicians Group, PLLC
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee Health Sciences Center, Dept. of Neurology
state: Tennessee
city: Memphis
country: United States
facility: UT Medical Group
state: Tennessee
city: Nashville
country: United States
facility: Access Clinical Trials, Inc
state: Tennessee
city: Dallas
country: United States
facility: Neurological Clinic of Texas, PA
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center, Dept. of Neuropsychiatry
state: Texas
city: Houston
country: United States
facility: University of Texas - Dept of Neurology
state: Texas
city: Irving
country: United States
facility: Baylor Medical Center of Irving
state: Texas
city: West Jordan
country: United States
facility: Epilepsy and Neurodevelopment, Inc.
state: Utah
city: Burlington
country: United States
facility: University of Vermont, College of Medicine, Clinical Neurophysiology Lab
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Healthcare
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington, Harborview Medical Center, Regional Epilepsy Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin, Dept. of Neurology
state: Wisconsin
Study officials:
References:
citation: Panebianco M, Prabhakar H, Marson AG. Rufinamide add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2020 Nov 8;11(11):CD011772. doi: 10.1002/14651858.CD011772.pub3.