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

NCT00327717 | Completed Phase 3 Results

• 1 other identifier: E2090-AS086-311
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 8

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).

Conditions

Partial Seizures

Keywords

Epilepsy; Partial seizures

Outcome Measures

Primary Outcomes (1)

• 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 (9)

• The Mean Percent Change From Baseline in Complex Partial (CP) Seizure Frequency

  Baseline and 16 weeks

• The Mean Percent Change From Baseline in Simple Partial (SP) Seizure Frequency

  Baseline and 16 weeks

• The Mean Percent Change From Baseline in Partial Seizures With Secondary Generalization (SGS)

  Baseline and 16 weeks

• Responder Rate

  Baseline and 16 weeks

• Mean Number of Seizure Free Days

  12 weeks

Study Arms (2)

Zonisamide 100 mg tablet

EXPERIMENTAL

Drug: Zonisamide

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

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.

Also known as: Zonegran

Zonisamide 100 mg tablet

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (8)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Peking Union Hospital

Beijing, Beijing Municipality, 100053, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, 200003, China

Location

Shanghai Hua-shan Hospital

Shanghai, Shanghai Municipality, 200040, China

Location

XiÆan Xijing Hospital

XiÆan, Shanxi, 710032, China

Location

Chengdu Huaxi Hospital

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Seizures; Epilepsy

Interventions

Zonisamide

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Takao Ishii, Asia regulatory affairs
• Organization: Eisai Co., Ltd.

81-3-3817-3914

Study Officials

• Di Hong

  Eisai China Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2006
• First Posted: May 18, 2006
• Study Start: September 1, 2006
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: August 15, 2014
• Results First Posted: August 15, 2014

Record last verified: 2014-08

Locations

CN (8)