Dose Response Study of Zonegran in Patients With Newly Diagnosed Epilepsy

A Double-Blind, Randomized, Multicenter, Parallel Group Study to Establish Dose-Response, Safety, and Efficacy of Zonegran (Zonisamide) as Monotherapy in Patients With Newly Diagnosed Epilepsy

The purpose of this study is to determine whether zonisamide alone is effective as a treatment for epilepsy in newly diagnosed cases.

Study Overview

• Status: Completed
• Conditions: Epilepsy, Complex Partial
• Intervention / Treatment: Drug: Zonisamide

Detailed Description

Epilepsy is characterized by repeated seizures caused by recurrent, abnormal, and excessive synchronous discharges from cerebral neurons. Seizures may be triggered by various causes such as CNS infections, fever, tumors, toxins, vascular disease, degenerative disease, trauma, or may be idiopathic. The type of seizure is usually defined by the initial event, the duration, alterations of consciousness, patterns of motor activity, and post-ictal symptoms. In addition, certain seizure types have characteristic EEG patterns. The International Classification of Epileptic Seizures classifies seizures as partial or generalized. Partial seizures are further classified as simple partial, complex partial (impaired consciousness), or partial seizures secondarily generalized. All partial seizures have onset in a discrete cortical region. Generalized seizures are bilaterally symmetrical and without focal onset and include absence seizures, myoclonic seizures, clonic seizures, tonic seizures, tonic-clonic seizures, and atonic seizures. The goals of treatment include the prevention of seizures, medical management of seizures, and management of the consequences of epilepsy. The study will be conducted with patients who have new onset epilepsy characterized by complex partial seizures and will attempt to characterize the relationship between zonisamide dose and seizure prevention and demonstrate monotherapy efficacy.

• Study Type: Interventional
• Enrollment: 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia, 13419
    • Tallinn Children's Hospital
  • Tartu, Estonia, 13419
    • Tartu University Hospital
• Hungary
  • Budapest, Hungary, 116
    • Semmelweis University Health Science Faculty
  • Budapest, Hungary, H1145
    • National Institute of Neurosurgery Epilepsy Center
• Lithuania
  • Kaunas, Lithuania, 3007
    • Kaunas Medical University Clinics
  • Vilnius, Lithuania, 2600
    • Vilnius University Hospital
• Ukraine
  • Kharkov, Ukraine, 31002
    • Kharkov State Medical University
  • Kharkov, Ukraine, 31068
    • Institute of Neurology, Psychiatry, and Narcology of AMS Ukraine
  • Kiev, Ukraine, 254655
    • Epilepsy Center
  • Odessa, Ukraine, 9
    • Odessa Medical University
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Epilepsy Center
    • Huntsville, Alabama, United States, 35801
      • North Alabama Neuroscience
    • Northport, Alabama, United States, 35476
      • Neurology Clinic, P.C.
  • California
    • Northridge, California, United States, 91325
      • Northridge Neurological Center
    • San Diego, California, United States, 92037
      • Coordinated Clinical Research
  • Florida
    • Maitland, Florida, United States, 32751
      • Neurology Associates
    • Panama City, Florida, United States, 32405
      • Bay Neurological Institute
    • St. Petersburg, Florida, United States, 33701
      • Suncoast Neuroscience Associates, Inc.
    • Tallahassee, Florida, United States, 32308
      • AMO Corporation
    • Tampa, Florida, United States, 33613
      • Florida Epilepsy & Seizure Disorder Center, PA
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Neurology & Headache Specialist of Atlanta, LLC
  • Illinois
    • Springfield, Illinois, United States, 62707
      • Southern Illinois University School of Medicine Dept. of Neurology
  • Kentucky
    • Louisville, Kentucky, United States, 40205
      • Louisville Neuroscience Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Health Care, Inc.
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • The Comprehensive Epilepsy Care Center
  • New York
    • Albany, New York, United States, 12205
      • Upstate Clinical Research Center
    • Orchard Park, New York, United States, 14127
      • Dent Neurological Institute
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Epilepsy Institute of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • River Hills Health Care
  • Pennsylvania
    • Greensburg, Pennsylvania, United States, 15601
      • Westmoreland Neurology Associates, Inc.
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • CNS Research, INC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Neurology Clinic of San Antonio
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Research Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • Neurology & Neurosurgery Associates of Tacoma, Inc. P.S.
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

• Patient able and willing to give written informed consent or assent as appropriate in accordance with ICH and GCP guidelines
• Patient with newly diagnosed epilepsy who has complex partial seizures (with or without secondary generalization)
• Patient must have at least two well-documented, unprovoked, clinically evaluated and classified complex partial seizures or one well-documented, unprovoked, clinically evaluated and classified complex partial seizure and an abnormal EEG consistent with the diagnosis of epilepsy occurring within one year prior to enrollment
• Patient must have received less than 2 weeks of prior AED therapy, which will be discontinued at study entry

• EEG changes consistent with the diagnosis of epilepsy:

  • For patients with two well-documented, unprovoked complex partial seizures within one year prior to enrollment, the EEG results may be normal at the time of testing but, in the opinion of the Investigator, the patient has epilepsy
  • For patients with one well-documented, unprovoked complex partial seizure within one year prior to enrollment, the EEG must be abnormal at the time of testing consistent with the diagnosis of epilepsy
• Patient age 16 years or greater
• In the opinion of the Investigator, the patient is in good health
• Female patients of child-bearing potential must not be pregnant (serum HCG negative) or lactating, and must be using a medically acceptable form of birth control such as abstinence, an adequate barrier method, or hormonal contraceptive; or female patients who are post-menopausal or have had surgical sterilization
• Patient or caregiver able to follow Investigator instruction, study procedures, maintain diary of concomitant medication use, and report adverse events

EXCLUSION CRITERIA

• History of status epilepticus
• Patient with simple partial seizures only
• A history of non-epileptic seizures (e.g. metabolic or pseudo-seizures)
• Progressive encephalopathy or findings consistent with progressive CNS disease or lesions (e.g. infection, demyelination, tumor)
• Clinically significant uncontrolled medical disease in the previous two years (including unstable cardiac, hematological, hepatic, or renal disease)
• History of acute intermittent porphyria, glucose-6-phosphate dehydrogenase deficiency or hemolytic anemia
• Renal insufficiency (serum creatinine > 2 mg/dL) or impaired liver function (SGPT/ALT > two times upper limit of normal)
• History of renal calculi
• Laboratory test results which, in the opinion of the Investigator, are clinically significant abnormalities
• History of alcohol or drug abuse
• Psychiatric illness or mood disorders requiring treatment in previous 6 months; history of suicide attempt or psychosis
• Use of benzodiazepines (intermittent use as a hypnotic or an PRN AED is allowed)
• Use of other investigational compounds, experimental drugs or devices within 30 days of the screening visit
• History of hypersensitivity or allergic reaction to sulfonamides
• Medical disorder, surgery or medication that might interfere with absorption, distribution, metabolism, or excretion of the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Collaborators and Investigators

• Sponsor: Eisai Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): October 1, 2004
• Study Completion (Actual): October 1, 2004

Study Registration Dates

• First Submitted: March 18, 2003
• First Submitted That Met QC Criteria: March 18, 2003
• First Posted (Estimate): March 19, 2003

Study Record Updates

• Last Update Posted (Estimate): July 18, 2011
• Last Update Submitted That Met QC Criteria: July 14, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Epilepsy; Monotherapy; AED; Complex Partial Seizures; anti-epilepsy drug
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsies, Partial; Epilepsy; Epilepsy, Complex Partial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Zonisamide
• Other Study ID Numbers: AN46046-304