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

Eisai

Status and phase: Completed; Phase 3

Conditions: Partial Seizures

Treatments: Drug: Zonisamide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00327717

E2090-AS086-311

Details and patient eligibility

About

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).

Enrollment: 240 patients

Sex: All

Ages: 16 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

240 participants in 2 patient groups, including a placebo group

Zonisamide 100 mg tablet

Experimental group

Treatment:

Drug: Zonisamide

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo