A Comparison of the Effectiveness and Safety of Topiramate and Phenytoin in Patients With New Onset Epilepsy Requiring Rapid Initiation of Antiepileptic Drug Treatment

Johnson & Johnson (J&J)

Status and phase

Completed

Phase 3

Conditions

Epilepsy

Treatments

Drug: topiramate, phenytoin

Study type

Interventional

Funder types

Industry

Identifiers

NCT00210782

CR004663

Details and patient eligibility

About

The purpose of this study is to compare the effectiveness and safety of two treatment regimens, topiramate as compared to phenytoin, in preventing seizures in patients with new-onset epilepsy who require rapid initiation of antiepileptic drug therapy. Reasons for requiring rapid initiation of treatment, rather than slowly increasing an antiepileptic drug to an effective dose, may include severe or frequent seizures, or high risk to the patient of recurrent seizures.

Full description

In this study, patients who have recently been diagnosed with epilepsy and who require rapid initiation of treatment will be randomized to receive either phenytoin or topiramate. Patients have an equal chance of receiving either medication. Phenytoin and topiramate have been approved by the FDA for treatment of epilepsy. The first phase of this study (lasting 28 days) is double-blind, meaning that neither the patient or the physician know which medication the patient is receiving. Phenytoin will be used according to the dosing recommendation in the package insert. Patients randomized into the phenytoin arm of this study, will receive a dose on day 1 of 1000mg phenytoin (given in 3 divided doses), an initiation dose recommended in the product labeling. This will be followed by 300mg of phenytoin on each subsequent day. Patients randomized into the topiramate arm of this study will receive 100mg of topiramate on day 1 and then continue to receive 100mg on each subsequent day. This is a relatively rapid initiation schedule of topiramate, but it is anticipated that it will be well tolerated and represents an appropriate regimen for comparison to patients in the phenytoin arm of the study. Patients will be carefully monitored for primary generalized tonic clonic seizures or complex partial onset seizures (two distinct epileptic seizure types) during the 28-day double-blind evaluation period of the trial. If a patient experiences a seizure during this 28 day period, they will either be taken out of the study, or be offered the option to receive a higher dose of topiramate in an open-label fashion. Open-label means that the patient and the physician will know what medication and what dose of the medication the patient is taking. All patients who do not experience a seizure during the 28 day period will be offered to receive open-label topiramate for an additional 12 weeks. The study hypothesis is that the proportion of patients who do not have a seizure within the 28 day double blind phase of the study will not differ between the 2 treatment groups. Topiramate 100 milligrams a day by mouth for 4 weeks; phenytoin 1000 milligrams to start, decreased to 300 milligrams a day by mouth for 4 weeks.

Enrollment

262 patients

Sex

All

Ages

12 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Seizures indicative of new-onset epilepsy (or epilepsy relapse) of untreated epilepsy
at least one but not more than 20 unprovoked seizures within past 3 months
weighing more than 110 pounds
considered to be a good candidate for rapid initiation of anti-seizure medication
able to swallow a tablet whole (without crushing it).

Exclusion criteria

Not having taken anti-seizure medications within the past 30 days
no provoking factors for seizures (presence of alcohol withdrawal, drug intoxication, acute meningitis or encephalitis, acute head injury or stroke, acute hypoxic/ischemic encephalopathy, or brain tumor)
no presence of active liver disease or serious kidney disease
not pregnant or breast-feeding
not using birth control.