Clinical trial NCT00236860: 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
Official title: Double-Blind Parallel Comparison of Topiramate 400 mg Twice Daily to Placebo in Patients With Refractory Partial Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Epilepsies, Partial
Seizures
Keywords: partial seizure disorder
brain diseases
topiramate
epilepsy
partial epilepsies
partial epilepsy
seizures
epileptic seizures
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2005-10-12
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* History of simple or complex partial epilepsy that has been documented or witnessed
* an electroencephalogram (EEG) during the preceding 5 years that has a pattern consistent with the diagnosis of partial epilepsy
* during an 8-week baseline phase, patient must have at least 8 partial seizures while maintaining therapeutic levels of antiepileptic drugs (AEDs) and have no more than one seizure-free interval of up to 3 weeks
* and no seizure-free interval longer than 3 weeks
* good physical health.

Exclusion Criteria:

* Patients having solely generalized seizures or lacking documentation of partial epilepsy
* patients with generalized tonic-clonic seizures or other generalized epilepsies in the absence of an EEG consistent with partial epilepsy
* generalized seizures, which are defined by the EEG wave pattern
* seizures that lack an abnormal pulsation pattern on EEG
* females who are capable of having children

Primary outcomes:
measure: Percent reduction in the average monthly seizure rate from baseline to end of treatment
Secondary outcomes:
measure: Percent of patients responding to treatment; patient's and investigator's global assessments at end of study rate; reduction in generalized seizureincidence of adverse events throughout study
Other outcomes:
Locations:
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Ben-Menachem E, Henriksen O, Dam M, Mikkelsen M, Schmidt D, Reid S, Reife R, Kramer L, Pledger G, Karim R. Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures. Epilepsia. 1996 Jun;37(6):539-43. doi: 10.1111/j.1528-1157.1996.tb00606.x.