Evaluating the Efficacy and Safety of Zonisamide in the T... | NCT00327717

NCT00327717

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
Zonisamide 100 mg tablet	Experimental		Drug: Zonisamide
Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Zonisamide	Drug	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.

Outcomes Module

Primary Outcomes

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	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 Outcomes

Measure	Description	Time Frame
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
The Mean Percent Change From Baseline in Simple Partial (SP) Seizure Frequency

Eligibility Module

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:

Adult male or female, 16 to 70 years old;
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);
Based on the retrospective subject diary, at least 4 partial seizures per month ( 4 weeks ) within 12 weeks prior to entry;
No more than 8 secondary generalized tonic, clonic, or tonic-clonic seizures per month within 12 weeks prior to entry;
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;
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;
Was able to count seizure frequencies;
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).
Signed written informed consent and agreed to comply with the protocol.

Exclusion criteria:

History or evidence of a progressive central nervous system (CNS) disease;
Nonepileptic seizures and pseudoepileptic seizures;
Severe mental retardation or unstable psychical status;
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;
History of malignant neoplastic disease;
Any condition that might interfere the pharmacokinetics (absorption, distribution, and/or excretion) of drugs, such as liver or kidney dysfunction, hypoproteinemia;
Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or history of hemolytic anemia or acute intermittent porphyria.
History of kidney stone;
History of alcohol or drug abuse within 2 years;
Sensitivity to sulfonamide medications or history of severe drug allergy;
Administration of monoamine oxidase inhibitor (MAOI), antidepressants or antipsychotic a psycho-tropic within 14 days prior to entry;
History of status epileptics in the past years or seizure clusters where individual seizures cannot be counted ;
History of zonisamide administration;
History of acetazolamide administration to treat epilepsy within 2 months prior to entry;
Joined the clinical trial of other AEDs within 30 days prior to entry;
Pregnant women or women in lactation;
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);
Inability of subject to return for scheduled visits or to comply with any other aspect of the protocol.
Subjects who, in the opinion of the investigator, were poor medical candidates or pose any other risk for therapy with an investigational drug.

Name	Affiliation	Role
Di Hong	Eisai China Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Peking University First Hospital		Beijing	Beijing Municipality	100034	China
Peking Union Hospital

ID	Title	Description
FG000	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.
FG001	Placebo	Patients in placebo group were titrated with placebo in the same way as in zonisamide group.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Full analysis set (FAS)

Posted

Median

Full Range

Percent Change

Baseline and 16 weeks

ID	Title	Description
OG000	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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.

ID	Term
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D013450	Sulfones
D013457