Clinical trial NCT00327717: Evaluating the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures
Official title: A Multicenter, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Partial Seizures
Keywords: Epilepsy
Partial seizures
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2006-05-18
Enrollment: 240
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: 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
timeFrame: Baseline and 16 weeks
Secondary outcomes:
measure: The Mean Percent Change From Baseline in Complex Partial (CP) Seizure Frequency
timeFrame: Baseline and 16 weeks
measure: The Mean Percent Change From Baseline in Simple Partial (SP) Seizure Frequency
timeFrame: Baseline and 16 weeks
measure: The Mean Percent Change From Baseline in Partial Seizures With Secondary Generalization (SGS)
timeFrame: Baseline and 16 weeks
measure: Responder Rate
timeFrame: Baseline and 16 weeks
measure: Mean Number of Seizure Free Days
timeFrame: 12 weeks
measure: Mean Percentage of Change in Seizure Free Days
timeFrame: 16 weeks
measure: Mean Time to First Seizure (Days)
timeFrame: 16 weeks
measure: Percentage of Seizure-free Participants During Fixed-dose Phase
timeFrame: 16 weeks
measure: Drop - Out Rate
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Hua-shan Hospital
state: Shanghai
city: XiÆan
country: China
facility: XiÆan Xijing Hospital
state: Shanxi
city: Chengdu
country: China
facility: Chengdu Huaxi Hospital
state: Sichuan
Study officials:
affiliation: Eisai China Inc.
name: Di Hong
role: STUDY_DIRECTOR
References: