Evaluating the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures

August 14, 2014 updated by: Eisai Inc.

A Multicenter, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

240

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100034
        • Peking University First Hospital
      • Beijing, Beijing, China, 100730
        • Peking Union Medical College Hospital
      • Beijing, Beijing, China, 100053
        • Peking Union Hospital
    • Chongqing
      • Chongqing, Chongqing, China, 400016
        • The First Affiliated Hospital of Chongqing Medical University
    • Shanghai
      • Shanghai, Shanghai, China, 200003
        • Shanghai Changzheng Hospital
      • Shanghai, Shanghai, China, 200040
        • Shanghai Hua-shan Hospital
    • Shanxi
      • XiÆan, Shanxi, China, 710032
        • XiÆan Xijing Hospital
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Chengdu Huaxi Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Experimental: Zonisamide 100 mg tablet
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.
Other Names:
  • Zonegran

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Percent Change From Baseline in All Partial Seizure Frequency (Complex Partial Seizures (CP)+ Simple Partial Seizures (SP) + Secondary Generalization Seizures (SGS)) During the Fixed-dose Phase
Time Frame: Baseline and 16 weeks
The median percent change in seizure frequency of all partial seizures (CP+SP+SGS) from baseline during the fixed-dose phase.
Baseline and 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Mean Percent Change From Baseline in Complex Partial (CP) Seizure Frequency
Time Frame: Baseline and 16 weeks
The Mean Percent Change in seizure frequency of CP from baseline during the fixed-dose phase.
Baseline and 16 weeks
The Mean Percent Change From Baseline in Simple Partial (SP) Seizure Frequency
Time Frame: Baseline and 16 weeks
The Mean percent change in seizure frequency of SP from baseline during the fixed-dose phase.
Baseline and 16 weeks
The Mean Percent Change From Baseline in Partial Seizures With Secondary Generalization (SGS)
Time Frame: Baseline and 16 weeks
The mean percent change in seizure frequency of SGS from baseline during the fixed-dose phase.
Baseline and 16 weeks
Responder Rate
Time Frame: Baseline and 16 weeks
Responder rate is defined as percentage of participants with >=50% reduction in seizure frequency from baseline.
Baseline and 16 weeks
Mean Number of Seizure Free Days
Time Frame: 12 weeks
Mean number of seizure free days per 28 day period during fixed dose phase
12 weeks
Mean Percentage of Change in Seizure Free Days
Time Frame: 16 weeks
16 weeks
Mean Time to First Seizure (Days)
Time Frame: 16 weeks
Mean time to first seizure during fixed dose phase
16 weeks
Percentage of Seizure-free Participants During Fixed-dose Phase
Time Frame: 16 weeks
Percentage of seizure-free participants during fixed-dose phase
16 weeks
Drop - Out Rate
Time Frame: 16 weeks
Number of Participants who dropped out of the study. In the Study drop-out rate is defined as number of participants.
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Di Hong, Eisai China Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

May 17, 2006

First Submitted That Met QC Criteria

May 17, 2006

First Posted (Estimate)

May 18, 2006

Study Record Updates

Last Update Posted (Estimate)

August 15, 2014

Last Update Submitted That Met QC Criteria

August 14, 2014

Last Verified

August 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Partial Seizures

Clinical Trials on Zonisamide

3
Subscribe