Rufinamide Given as Adjunctive Therapy in Patients With Refractory Partial Seizures

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00334958
First received: June 7, 2006
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

The primary objective of this study is to evaluate the effect of rufinamide on total partial seizure frequency in adolescent and adult patients with refractory partial onset seizures currently inadequately treated with a maximum of three stable antiepileptic medications. Secondary objectives are to evaluate the effect of rufinamide on secondary and exploratory outcomes, to confirm the safety profile of rufinamide, and to assess the relationship between rufinamide plasma concentration and efficacy.


Condition Intervention Phase
Epilepsy
Drug: Placebo
Drug: Rufinamide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Parallel-Group Study of Rufinamide Given as Adjunctive Therapy in Patients With Refractory Partial Seizures

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Percentage Change in Total Partial Seizure Frequency Per 28 Days During Maintenance Phase Relative to the Baseline Phase [ Time Frame: Baseline, Days 13 to 96 ] [ Designated as safety issue: No ]
    There are 2 major categories of seizures in epilepsy: generalized and partial (focal) seizures. The most frequent type is partial onset seizures. For inclusion in this study, participants needed to have a diagnosis of epilepsy with partial onset seizures with or without secondarily generalized seizures according to the International League Against Epilepsy Classification of Epileptic Seizures. Seizure data was collected via patient diary, which was used to record daily seizure count and type.


Secondary Outcome Measures:
  • 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 [ Time Frame: Baseline, Days 13 to 96 ] [ Designated as safety issue: No ]
    There are 2 major categories of seizures in epilepsy: generalized and partial (focal) seizures. The most frequent type is partial onset seizures. For inclusion in this study, participants needed to have a diagnosis of epilepsy with partial onset seizures with or without secondarily generalized seizures according to the International League Against Epilepsy Classification of Epileptic Seizures. Seizure data was collected via patient diary, which was used to record daily seizure count and type.

  • Log10 Transformed Total Partial Seizure Frequency Per 28 Days During the Baseline Phase and Maintenance Phase [ Time Frame: Days 13 to 96 ] [ Designated as safety issue: No ]
    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.

  • Reduction From Baseline in Total Partial Seizure Frequency Rate (RRATIO) During Maintenance Phase [ Time Frame: Baseline, Days 13 to 96 ] [ Designated as safety issue: No ]
    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


Enrollment: 356
Study Start Date: February 2006
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
BID for 12-day Titration Phase and 12-week Maintenance Phase.
Active Comparator: Rufinamide Drug: Rufinamide
400 mg twice daily (BID) orally uptitrated every 3 days in 400 mg BID increments up to 1600 mg BID (total daily dose of 3200 mg/day) over 12-day Titration Phase; followed by 1600 mg BID over 12-week Maintenance Phase.
Other Name: E2080

  Eligibility

Ages Eligible for Study:   12 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334958

  Show 77 Study Locations
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Francesco Bibbiani, M.D. Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00334958     History of Changes
Other Study ID Numbers: E2080-A001-301
Study First Received: June 7, 2006
Results First Received: April 16, 2012
Last Updated: January 2, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on August 28, 2014