Rufinamide Given as Adjunctive Therapy in Participants With Refractory Partial Seizures

Epilepsy Clinical Trial

Official title:

A Double-Blind, Placebo-Controlled, Parallel-Group Study of Rufinamide Given as Adjunctive Therapy in Patients With Refractory Partial Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00334958
• Other study ID #: E2080-A001-301
• Secondary ID: 2016-004944-12
• Status: Completed
• Phase: Phase 3
• Start date: February 13, 2006
• Est. completion date: May 20, 2009

Study information

• Verified date: May 2021
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 356
• Est. completion date: May 20, 2009
• Est. primary completion date: May 20, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• Placebo
For the 12-day Titration Phase, one matching placebo tablet will be administered twice daily and increased by 1 matching placebo tablet every 3 days up to maximum of 4 matching placebo tablets twice daily (placebo tablet matched to rufinamide total daily dose of 3200 mg). For the 12 week maintenance phase, 4 placebo tablets matching to rufinamide maintenance doses of 1600 mg twice daily (3200 mg total daily dose) will be administered. Similar to the dose reduction permitted in the rufinamide group, participants in placebo group will be allowed only during the Titration Phase to have the dose reduced to 3 placebo tablets twice daily.
• Rufinamide
For the titration phase, Rufinamide will be administered orally in doses starting with 400 mg twice daily and increased every 3 days in 400 mg twice daily increments up to 1600 mg twice daily (total daily dose 3200 mg). For the Maintenance Phase, maintenance doses of 1600 mg twice daily (3200 mg total daily dose) will be administered. Participants unable to tolerate the target dose (3200 mg/day) will be allowed only during the Titration Phase to have the dose reduced to 3 tablets twice daily (corresponding to a dose of 2400 mg/day in the rufinamide group).

Locations

Country	Name	City	State
United States	Blair Medical Associates, Inc.	Altoona	Pennsylvania
United States	Mcfarland Clinic	Ames	Iowa
United States	Asheville Neurology Specialists, PA	Asheville	North Carolina
United States	Child Neurology Associates, PC	Atlanta	Georgia
United States	Medical College of Georgia, Dept. of Neurology	Augusta	Georgia
United States	John Hopkins Hospital, Dept. of Neurology	Baltimore	Maryland
United States	Boston University Medical Center, Dept. of Neurology	Boston	Massachusetts
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Bradenton Research Center	Bradenton	Florida
United States	Montefiore Medical Center, Albert Einstein College of Medicine	Bronx	New York
United States	Fletcher Allen Healthcare	Burlington	Vermont
United States	University of Vermont, College of Medicine, Clinical Neurophysiology Lab	Burlington	Vermont
United States	Medical Associates of North Georgia	Canton	Georgia
United States	University of North Carolina at Chapel Hill, Dept. of Neurology	Chapel Hill	North Carolina
United States	The Comprehensive Epilepsy Care Center for Children and Adults	Chesterfield	Missouri
United States	Children's Memorial Hospital, Northwest University	Chicago	Illinois
United States	Cleveland Clinic Foundation, Dept. of Neurology	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Neurological Clinic of Texas, PA	Dallas	Texas
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Duke Health Center at Morreene Road	Durham	North Carolina
United States	Texas Tech University Health Sciences Center, Dept. of Neuropsychiatry	El Paso	Texas
United States	Neuro-Pain Medical Center, Inc.	Fresno	California
United States	University of Florida, Dept. of Neurology	Gainesville	Florida
United States	Mid-South Physicians Group, PLLC	Germantown	Tennessee
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Ronald Schwartz, M.D.	Hattiesburg	Mississippi
United States	The Queen's Medical Center	Honolulu	Hawaii
United States	University of Massachusetts, Neurology Associates	Hopedale	Massachusetts
United States	University of Texas - Dept of Neurology	Houston	Texas
United States	Baylor Medical Center of Irving	Irving	Texas
United States	University of Florida, The Neuroscience Institute at Shands	Jacksonville	Florida
United States	Five Towns Neuroscience Research	Lawrence	New York
United States	Dartmouth Medical School Neuroscience Center	Lebanon	New Hampshire
United States	University of Kentucky, Dept. of Neurology	Lexington	Kentucky
United States	Clinical Trials, Inc	Little Rock	Arkansas
United States	Pediatric Neurologists of Palm Beach	Loxahatchee Groves	Florida
United States	University of Wisconsin, Dept. of Neurology	Madison	Wisconsin
United States	University of Tennessee Health Sciences Center, Dept. of Neurology	Memphis	Tennessee
United States	UT Medical Group	Memphis	Tennessee
United States	University of Minnesota, Dept. of Neurology	Minneapolis	Minnesota
United States	University of South Alabama Medical Center	Mobile	Alabama
United States	Access Clinical Trials, Inc	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	New York University Medical Centre, Comprehensive Epilepsy Center	New York	New York
United States	Weill Cornell Medical Center, Comprehensive Epilepsy Center	New York	New York
United States	Neurology Clinic PC	Northport	Alabama
United States	Advocate Hope Children's Hospital	Oak Lawn	Illinois
United States	Neurology Center	Oceanside	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nemours Children's Clinic	Orlando	Florida
United States	Pediatric Neurology - PA	Orlando	Florida
United States	Bay Medical Center	Panama City	Florida
United States	Advocate Lutheran General Children's Hospital	Park Ridge	Illinois
United States	Hospital of The University of Pennsylvania	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania, Dept. of Neurology	Philadelphia	Pennsylvania
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Mayo Clinic Epilepsy and Neurology	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh - Dept of Pediatrics	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	Minnesota Epilepsy Group, PC	Saint Paul	Minnesota
United States	California Pacific Epilepsy	San Francisco	California
United States	University of Washington, Harborview Medical Center, Regional Epilepsy Center	Seattle	Washington
United States	Saint John's Medical Research	Springfield	Missouri
United States	Southern Illinois University Neurology and Pharmacology	Springfield	Illinois
United States	University of Southern Florida, Dept. of Neurology	Tampa	Florida
United States	Medical University of Ohio at Toledo, Dept. of Neurology	Toledo	Ohio
United States	University of Arizona, Dept. of Neurology	Tucson	Arizona
United States	Children's National Medical Center	Washington	District of Columbia
United States	Georgetown University Hospital, Dept. of Neurology	Washington	District of Columbia
United States	Epilepsy and Neurodevelopment, Inc.	West Jordan	Utah
United States	Via Christi Comprehensive Epilepsy Center	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Change in Total Partial Seizure Frequency Per 28 Days During Maintenance Phase Relative to the Baseline Phase	Seizure data was collected via patient diary, which was used to record daily seizure count and type. Intent-to-treat (ITT) population: All randomized participants who had baseline Patient Seizure Diary data and had at least completed the titration period.	Baseline, Days 13 to 96
Secondary	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	Seizure data was collected via patient diary, which was used to record daily seizure count and type.	Baseline, Days 13 to 96
Secondary	Log10 Transformed Total Partial Seizure Frequency Per 28 Days During the Baseline Phase and Maintenance Phase	Total partial seizure frequencies per 28 days during the double-blind Maintenance and Baseline Phases were transformed using logarithms to the base 10 (log10), because it was expected from previous studies that the results would not be normally distributed.	Days 13 to 96
Secondary	Reduction From Baseline in Total Partial Seizure Frequency Rate (RRATIO) During Maintenance Phase	RRATIO= 100*(T-B)/(T+B) where T= total seizure frequency per 28 days during the Maintenance Phase, and B=total seizure frequency per 28 days during the Baseline Phase.	Baseline, Days 13 to 96