A Study of the Efficacy and Safety of Topiramate as add-on Therapy in the Treatment of Epilepsy Patients With Difficult to Treat, Partial-onset Seizures
Condition: Epilepsy; Epilepsies, Partial; Seizures
MeSH terms: Epilepsy; Seizures; Epilepsies, Partial
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the efficacy and safety of topiramate as add-on
      therapy in epilepsy patients with difficult to treat, partial-onset seizures who are taking
      one or two standard anti-epileptic drugs.
    

Detailed description: 
      Epilepsy is characterized by seizures, which are abnormal electrical discharges in the brain
      that temporarily disrupt normal brain function. Seizures are classified as "generalized,"
      originating in both sides of the brain simultaneously, or "partial-onset," starting in one
      area of the brain. Antiepilepsy medications, such as topiramate, are selected based on
      seizure type. This is a double-blind, placebo-controlled study in adult patients with
      difficult to treat partial epilepsy that includes a baseline phase and a treatment phase.
      During the baseline phase (8 weeks duration), patients receive their one or two standard
      antiepileptic drugs (AEDs), such as phenytoin, carbamazepine, phenobarbital, primidone, or
      valproic acid. Patients who continue to have seizures during treatment with standard AEDs
      proceed into the double-blind treatment phase. Patients then receive topiramate or placebo at
      a dosage of 100-milligrams (mg) once daily, increasing gradually over 5 weeks to 4 tablets
      twice daily (800 mg/day) or maximum tolerated dose, and maintained on that dose for 8 weeks
      (13 weeks is the total duration of the double-blind phase), while continuing on their
      standard AED regimen. Assessments of effectiveness include the percent reduction in the
      average monthly seizure rate, percent of patients responding to treatment (having equal to or
      greater than 50% reduction in seizure rate), and the patient's and investigator's global
      assessments of medication at end of study. Safety assessments include the incidence of
      adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry,
      urinalysis), neurologic examinations, and vital sign measurements (blood pressure, pulse,
      temperature) weekly during the treatment phase. The study hypothesis is that topiramate,
      taken as add-on therapy to treatment with AEDs, will significantly reduce seizure frequency,
      compared with placebo, in patients with refractory partial epilepsy: that is, in patients who
      continue to have seizures despite treatment with a first-line AEDs. In addition, it is
      hypothesized that topiramate will be well tolerated. Topiramate, 100 mg oral tablets, or
      matching placebo tablets. Dosage begins at 100 mg once daily and increases gradually over 5
      weeks to 4 tablets twice daily (800 mg/day, maximum) or maximum tolerated dose for an
      additional 8 weeks. Doses may be increased or decreased at investigator's discretion.
    

Intervention name(s): topiramate
Intervention type(s): Drug
Intervention MeSH terms: Topiramate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: partial seizure disorder; brain diseases; topiramate; epilepsy; partial epilepsies; partial epilepsy; seizures; epileptic seizures