Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Study)

NCT00566254 | Completed Phase 3 Results

• 2 other identifiers: E2090-E044-3122006-002515-27
• Study Type: interventional
• Target: 207
• Locations: 8 countries
• Sites: 41

Brief Summary

The purpose of this study is to compare the safety and efficacy of zonisamide with placebo.

Conditions

Epilepsy; Paediatric Partial Onset Seizures

Keywords

Epilepsy; paediatric; partial onset seizures

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Decrease From Baseline in 28-day Seizure Frequency of =50%(Responder) in the Maintenance Period(LOCF)

  A participant with a decrease from baseline in seizure frequency of =50 % was considered a responder. Participants' parent or guardian maintained a seizure diary recording the date, number, and type of seizures the subject had. The primary analysis assessed the percent of responders in the Maintenance Period (28- day seizure frequency in Week 8 to Week 20 compared to Week -8 to Week 0 at Last Observation Carried Forward (LOCF)). Seizure frequency of simple partial, complex partial, and partial seizures with secondary generalization were assessed.

  Baseline (Week -8 to Week 0), and Week 8 to Week 20

Secondary Outcomes (3)

• Median Percent Change From Baseline in the 28-day Seizure Frequency During the Maintenance Period (LOCF)

  Baseline (Week -8 to Week 0) and Week 8 to Week 20

• Percent of Participants With =50% to < 75% and = 75% Decrease From Baseline in 28-day Seizure Frequency During the Maintenance Period(LOCF)

  Baseline (Week -8 to Week 0) and Week 8 to Week 20

• Percent of Participants With =25% and =100% Increase From Baseline in 28-day Seizure Frequency During the Maintenance Period (LOCF)

  Baseline (Week -8 to Week 0) and Week 8 to Week 20

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.

Drug: Placebo

Zonisamide

EXPERIMENTAL

Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.

Drug: Zonisamide

Interventions

Zonisamide DRUG

8mg/kg per day for approximately 24 weeks.

Also known as: Zonegran

Zonisamide

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject is male or female aged 6-17 years inclusive.
• Parent/guardian is willing to sign an approved informed consent form, and accompany the subject on all study visits.
• Subject is willing to give informed (written or verbal) assent and if appropriate written informed consent.
• Subject has a clinical diagnosis of epilepsy with partial-onset seizures with or without secondary generalized seizures according to the International League Against Epilepsy's Classification of Epileptic Seizures (1981).
• Diagnosis has been established by clinical history, electroencephalogram (EEG) and computed tomography/ magnetic resonance imaging (CT/MRI) of the brain consistent with localization related epilepsy.
• Subject has \> four (simple or complex) partial seizures (with or without secondary generalization) per month over the eight week Screening Period with at least one seizure in each four week period and with no 21 day period being seizure free.
• Subject is taking a stable regimen of one or two other AEDs for at least one month prior to Visit 1 (start of the Screening Period).
• NOTE: If using a vagal nerve stimulator (VNS), it must have been implanted for at least five months and stimulator parameters must remain unchanged for at least one month prior to Visit 1 (start of the Screening Period), and throughout the entire study period. VNS will be considered as one AED for the purposes of this study.
• Subject is in general good health as determined by medical history, physical exam and screening laboratory results.
• Parent/guardian is willing and able to complete a seizure diary for the duration of the study.

You may not qualify if:

• Subject of body weight \< 20 kg at the Screening Visit.
• Subject is unable to swallow capsules.
• Subject has progressive neurological disease (determined by diagnosis or a pre-existing brain image such as a CT scan or MRI).
• Subject has a history of idiopathic generalized epilepsy as defined by the International League Against Epilepsy (ILAE).
• Subjects with Lennox-Gastaut syndrome, absence, myoclonic, clonic and/or tonic (other than secondary generalized) and atonic seizures.
• Subject has psychogenic seizures
• Subject has a history of status epilepticus within a year of the Screening Visit whilst taking AEDs.
• Subject has seizures that only occur in clustered patterns, or has seizures that are too close together to count accurately.
• Subject has a history of renal calculi or renal insufficiency (creatinine levels \>194 µmol/l (1.5 mg1/dl).
• Subject had a predisposing condition that might interfere with absorption, distribution, or excretion of zonisamide.
• Subject has a history of psychiatric illness.
• Subject has a history of suicide attempt.
• Female subject who is pregnant or lactating.
• Subject has a history of demonstrated non-compliance with treatment or, the subject, parent or legal guardian can be reasonably expected not to be compliant with study procedures or to complete the study.
• Female subject of 10 years of age or greater or of child bearing potential (i.e., started menses) and is not taking or prepared to take a medically acceptable form of contraception (i.e., oral contraceptive pill, surgical sterilization, an implant or an injected form of contraception, or intrauterine device), or who is not prepared to abstain from sexual activity for the duration of the study and one month after last administration of study medication.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (43)

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Brussels, 1020, Belgium

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Brussels, 1090, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Tallinn, 13419, Estonia

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Tartu, 51014, Estonia

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Bordeaux, 33076, France

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Garches, 92380, France

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Lille, 59037, France

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Marseille, 13385, France

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Paris, 75015, France

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Rouen, 76031, France

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Budapest, 1025, Hungary

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Budapest, 1097, Hungary

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Budapest, 1143, Hungary

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Debrecen, 4012, Hungary

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Miskolc, 3526, Hungary

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Pécs, 7623, Hungary

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Bologna, 40133, Italy

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Brescia, 25123, Italy

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Florence, 50132, Italy

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Mantova, 40100, Italy

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Milan, 20133, Italy

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Pavia, 27100, Italy

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Riga, LV-1004, Latvia

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Valmiera, LV-4201, Latvia

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Dansk, 80-952, Poland

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Katowice, 40-752, Poland

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Olsztyn, 10-959, Poland

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Poznan, 60-355, Poland

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Poznan, 61-493, Poland

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Warsaw, 04-730, Poland

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Barcelona, 08950, Spain

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Madrid, 28040, Spain

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Madrid, 2804, Spain

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Murcia - El Palmar, 30120, Spain

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Santander, 39008, Spain

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Seville, 41006, Spain

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Dnipro, 49027, Ukraine

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Kharkiv, 61068, Ukraine

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Kharkiv, 61153, Ukraine

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Lviv, 79010, Ukraine

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Odesa, 65031, Ukraine

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MeSH Terms

Conditions

Epilepsy

Interventions

Zonisamide

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; 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: Eisai Inc.
• Organization: Eisai Call Center

888-422-4743

Study Officials

• Joanna Segieth, PhD

  Eisai Limited

  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: November 29, 2007
• First Posted: December 3, 2007
• Study Start: December 1, 2008
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: May 13, 2013
• Results First Posted: December 11, 2012

Record last verified: 2013-02

Locations

BE (4); UA (5); PL (6); HU (6); ES (6); FR (6); LA (2); IT (6)