Evaluating the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures
Condition: Partial Seizures
MeSH terms: Seizures
Intervention: Zonisamide; Placebo
Intervention description: Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.; Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Intervention MeSH terms: Zonisamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 240.0
Sex: All
Minimum age: 16 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Epilepsy; Partial seizures

Summary:

      The objectives of this trial are to evaluate the safety and efficacy of Zonisamide as
      adjunctive therapy in medically refractory patients receiving other antiepileptic drugs
      (AEDs).
    

Eligibility criteria:

        According to the International League Against Epilepsy (ILAE) classification of seizure
        type (1981) and international classification of epilepsies and epileptic syndromes (ILAE,
        1989), definite diagnosis of partial seizures (with or without secondary generalized
        seizures) refractory to current anti epilepsy drug (AED) therapy.

        Inclusion criteria:

          1. Adult male or female, 16 to 70 years old;

          2. Classified according to the ILAE classification of seizure type (1981) and
             international classification of epilepsy and epileptic syndromes (ILAE, 1989) into
             partial seizures (with or without secondary generalized seizures);

          3. Based on the retrospective subject diary, at least 4 partial seizures per month ( 4
             weeks ) within 12 weeks prior to entry;

          4. No more than 8 secondary generalized tonic, clonic, or tonic-clonic seizures per month
             within 12 weeks prior to entry;

          5. Antiepileptic therapy including at least 1-2 concomitant AEDs and were on a stable
             dose(s) of the same AEDs for the 3 months prior to enrollment;

          6. Had performed electro encephalogram (EEG) within 6 months prior to entry, and computer
             tomography (CT) or magnetic resonance imaging (MRI) examination to mainly exclude
             space-occupying disease;

          7. Was able to count seizure frequencies;

          8. Women with child bearing potential, were not to be pregnant or nursing, and must have
             agreed to practice during the study a reliable form of contraception (oral
             contraceptive, condom, intrauterine device or diaphragm).

          9. Signed written informed consent and agreed to comply with the protocol.

        Exclusion criteria:

          1. History or evidence of a progressive central nervous system (CNS) disease;

          2. Nonepileptic seizures and pseudoepileptic seizures;

          3. Severe mental retardation or unstable psychical status;

          4. Clinically significant cardiac, hepatic, renal, or hematological disease, uncontrolled
             hypertension (systolic blood pressure (SBP) ≥150 and/or diastolic blood pressure (DBP)
             ≥100mmHg), Symptomatic ischemic heart disease, cerebral infarction or atherosclerosis
             obliterans;

          5. History of malignant neoplastic disease;

          6. Any condition that might interfere the pharmacokinetics (absorption, distribution,
             and/or excretion) of drugs, such as liver or kidney dysfunction, hypoproteinemia;

          7. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or history of hemolytic anemia
             or acute intermittent porphyria.

          8. History of kidney stone;

          9. History of alcohol or drug abuse within 2 years;

         10. Sensitivity to sulfonamide medications or history of severe drug allergy;

         11. Administration of monoamine oxidase inhibitor (MAOI), antidepressants or antipsychotic
             a psycho-tropic within 14 days prior to entry;

         12. History of status epileptics in the past years or seizure clusters where individual
             seizures cannot be counted ;

         13. History of zonisamide administration;

         14. History of acetazolamide administration to treat epilepsy within 2 months prior to
             entry;

         15. Joined the clinical trial of other AEDs within 30 days prior to entry;

         16. Pregnant women or women in lactation;

         17. Abnormal clinical laboratory values with clinical significance judged by investigators
             (for example, if abnormal hepatic function is caused by concurrent other AEDs, the
             abnormal value within 2 times of normal could be acceptable);

         18. Inability of subject to return for scheduled visits or to comply with any other aspect
             of the protocol.

         19. Subjects who, in the opinion of the investigator, were poor medical candidates or pose
             any other risk for therapy with an investigational drug.