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

Partial Seizures Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00327717
• Other study ID #: E2090-AS086-311
• Status: Completed
• Phase: Phase 3
• First received: May 17, 2006
• Last updated: August 14, 2014
• Start date: September 2006
• Est. completion date: May 2008

Study information

• Verified date: August 2014
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Partial Seizures
• Seizures

Intervention

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.
• Placebo
Patients in placebo group were titrated with placebo in the same way as in zonisamide group.

Locations

Country	Name	City	State
China	Peking Union Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Chengdu Huaxi Hospital	Chengdu	Sichuan
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Shanghai Changzheng Hospital	Shanghai	Shanghai
China	Shanghai Hua-shan Hospital	Shanghai	Shanghai
China	XiÆan Xijing Hospital	XiÆan	Shanxi

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	No
Secondary	The Mean Percent Change From Baseline in Complex Partial (CP) Seizure Frequency	The Mean Percent Change in seizure frequency of CP from baseline during the fixed-dose phase.	Baseline and 16 weeks	No
Secondary	The Mean Percent Change From Baseline in Simple Partial (SP) Seizure Frequency	The Mean percent change in seizure frequency of SP from baseline during the fixed-dose phase.	Baseline and 16 weeks	No
Secondary	The Mean Percent Change From Baseline in Partial Seizures With Secondary Generalization (SGS)	The mean percent change in seizure frequency of SGS from baseline during the fixed-dose phase.	Baseline and 16 weeks	No
Secondary	Responder Rate	Responder rate is defined as percentage of participants with >=50% reduction in seizure frequency from baseline.	Baseline and 16 weeks	No
Secondary	Mean Number of Seizure Free Days	Mean number of seizure free days per 28 day period during fixed dose phase	12 weeks	No
Secondary	Mean Percentage of Change in Seizure Free Days		16 weeks	No
Secondary	Mean Time to First Seizure (Days)	Mean time to first seizure during fixed dose phase	16 weeks	No
Secondary	Percentage of Seizure-free Participants During Fixed-dose Phase	Percentage of seizure-free participants during fixed-dose phase	16 weeks	No
Secondary	Drop - Out Rate	Number of Participants who dropped out of the study. In the Study drop-out rate is defined as number of participants.	16 weeks	No