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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00327717
First received: May 17, 2006
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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).


Condition Intervention Phase
Partial Seizures
Drug: Zonisamide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    The median percent change in seizure frequency of all partial seizures (CP+SP+SGS) from baseline during the fixed-dose phase.


Secondary Outcome Measures:
  • The Mean Percent Change From Baseline in Complex Partial (CP) Seizure Frequency [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    The Mean Percent Change in seizure frequency of CP from baseline during the fixed-dose phase.

  • The Mean Percent Change From Baseline in Simple Partial (SP) Seizure Frequency [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    The Mean percent change in seizure frequency of SP from baseline during the fixed-dose phase.

  • The Mean Percent Change From Baseline in Partial Seizures With Secondary Generalization (SGS) [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    The mean percent change in seizure frequency of SGS from baseline during the fixed-dose phase.

  • Responder Rate [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    Responder rate is defined as percentage of participants with >=50% reduction in seizure frequency from baseline.

  • Mean Number of Seizure Free Days [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Mean number of seizure free days per 28 day period during fixed dose phase

  • Mean Percentage of Change in Seizure Free Days [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Mean Time to First Seizure (Days) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Mean time to first seizure during fixed dose phase

  • Percentage of Seizure-free Participants During Fixed-dose Phase [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Percentage of seizure-free participants during fixed-dose phase

  • Drop - Out Rate [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Number of Participants who dropped out of the study. In the Study drop-out rate is defined as number of participants.


Enrollment: 240
Study Start Date: September 2006
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zonisamide 100 mg tablet Drug: Zonisamide
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 Name: Zonegran
Placebo Comparator: Placebo Drug: Placebo
Patients in placebo group were titrated with placebo in the same way as in zonisamide group.

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00327717

Locations
China, Beijing
Peking Union Hospital
Beijing, Beijing, China, 100053
Peking Union Medical College Hospital
Beijing, Beijing, China, 100730
Peking University First Hospital
Beijing, Beijing, China, 100034
China, Chongqing
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing, China, 400016
China, Shanghai
Shanghai Changzheng Hospital
Shanghai, Shanghai, China, 200003
Shanghai Hua-shan Hospital
Shanghai, Shanghai, China, 200040
China, Shanxi
XiÆan Xijing Hospital
XiÆan, Shanxi, China, 710032
China, Sichuan
Chengdu Huaxi Hospital
Chengdu, Sichuan, China, 610041
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Di Hong Eisai China Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00327717     History of Changes
Other Study ID Numbers: E2090-AS086-311
Study First Received: May 17, 2006
Results First Received: October 28, 2010
Last Updated: August 14, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Eisai Inc.:
Epilepsy
Partial seizures

Additional relevant MeSH terms:
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Zonisamide
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014