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

This study has been completed.
Sponsor:
Collaborator:
Ortho-McNeil Neurologics, Inc.
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00210782
First received: September 13, 2005
Last updated: June 8, 2011
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Epilepsy
Drug: topiramate, phenytoin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Double-blind Trial Comparing the Efficacy, Tolerability and Safety of Monotherapy Topiramate Versus Phenytoin in Subjects With Seizures Indicative of New Onset Epilepsy

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • The primary outcome parameter is the time to first seizure during the double blind phase of the study. The statistical evaluation will analyze if there is a significant difference in the proportion of patients being seizure free between both medications.

Secondary Outcome Measures:
  • Effect of sex, age, baseline weight, baseline seizure type, and duration since first diagnosis of epilepsy on the time to seizure.

Enrollment: 262
Study Start Date: June 2004
Study Completion Date: August 2007
Detailed 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.

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00210782

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Ortho-McNeil Neurologics, Inc.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00210782     History of Changes
Other Study ID Numbers: CR004663
Study First Received: September 13, 2005
Last Updated: June 8, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
epilepsy
seizures
epileptic seizures
complex partial seizures
generalized tonic-clonic seizures

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Phenytoin
Topiramate
Anti-Obesity Agents
Anticonvulsants
Cardiovascular Agents
Central Nervous System Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sodium Channel Blockers
Therapeutic Uses
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on November 20, 2014