Epilepsy; Paediatric Partial Onset SeizuresPhase 3NCT00566254
Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Study)
A Phase 3 study testing Zonisamide in people with Epilepsy; Paediatric Partial Onset Seizures, run by Eisai Inc. at 43 sites in 9 countries.
Trial summary
The purpose of this study is to compare the safety and efficacy of zonisamide with placebo. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Epilepsy; Paediatric Partial Onset Seizures
- What is being tested?
- Zonisamide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 207 participants
- Where
- 43 sitesin 9 countries
- Study dates
- Dec 2008to Mar 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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
Show all 32Show fewer
- 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.
- NOTE: Should a female subject become of childbearing potential during the study, they must be reconsented in order to give consent to undergo pregnancy testing and either confirm abstinence or receive medically appropriate form of contraception.
- Subject has clinically significant abnormal laboratory values at the Screening Visit.
- Subject has received previous treatment with zonisamide.
- Subject is treated with a ketogenic diet or is likely to have surgery for epilepsy in the trial period.
- Subject requires frequent rescue benzodiazepines (> than once per week).
- Concomitant use of felbamate or use of felbamate within 2 months prior to Visit 1.
- Subject has elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN).
- Subject has evidence of significant active and unstable haematological disease; i.e., white blood cell (WBC) count < 2500/µL or an absolute neutrophil count < 1000/µL
- Subject with clinically significant active hepatic disease, cardiovascular, metabolic, respiratory, renal, endocrinological and gastrointestinal diseases or any other clinically significant organic disease, within 30 days prior to the Screening Visit.
- Subjects with known or suspected history of alcoholism or drug abuse within the previous two years, or a positive finding on urinary drug screening of any drugs other than prescribed medications.
- Subjects with any other condition that would make them, in the opinion of the Investigator unsuitable for this study.
- Subjects who have participated in a clinical trial involving administration of an investigational compound (including zonisamide) within three months of the Screening Visit.
- Subjects with a known or suspected hypersensitivity to zonisamide, or sulphonamides.
- Subjects taking acetazolamide, any carbonic anhydrase inhibitors e.g. topiramate, and any drugs with anticholinergic activity.
- Subjects who do not have a complete seizure diary during the Screening Period.
- Subjects with active and/or insufficiently treated neurocysticerosis or intercraniel tubiculosis. Note: subjects who have completed a curative antihelminthic or antituberculous treatment course more than 3 months before screening and who are free of signs and symptoms of active infection (including on a post treatment CT/MRI scan), may be enrolled in the study.
- Subjects taking antipsychotics, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and benzodiazepines with barbiturates and amphetamines for disease other than epilepsy within 3 months of screening.
Trial locations and contacts
43 sites in 9 countries.
43 sites in 9 countries
France6 sites
Study site
Bordeaux, 33076
Study site
Garches, 92380
Study site
Lille, 59037
Study site
Marseille, 13385
Study site
Paris, 75015
Study site
Rouen, 76031
Hungary6 sites
Study site
Budapest, 1025
Study site
Budapest, 1097
Study site
Budapest, 1143
Study site
Debrecen, 4012
Study site
Miskolc, 3526
Study site
Pécs, 7623
Italy6 sites
Study site
Bologna, 40133
Study site
Brescia, 25123
Study site
Florence, 50132
Study site
Mantua, 40100
Study site
Milan, 20133
Study site
Pavia, 27100
Poland6 sites
Study site
Dansk, 80-952
Study site
Katowice, 40-752
Study site
Olsztyn, 10-959
Study site
Poznan, 60-355
Study site
Poznan, 61-493
Study site
Warsaw, 04-730
Spain6 sites
Study site
Barcelona, 08950
Study site
Madrid, 28040
Study site
Madrid, 2804
Study site
Murcia - El Palmar, 30120
Study site
Santander, 39008
Study site
Seville, 41006
Ukraine5 sites
Study site
Dnipro, 49027
Study site
Kharkiv, 61068
Study site
Kharkiv, 61153
Study site
Lviv, 79010
Study site
Odesa, 65031
Belgium4 sites
Study site
Brussels, 1020
Study site
Brussels, 1090
Study site
Ghent, 9000
Study site
Leuven, 3000
About this study
Official title: A Double-blind, Randomised, Placebo-controlled, Multi-centre Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures
The purpose of this study is to compare the safety and efficacy of zonisamide with placebo.
Read the detailed description
This will be a double-blind, randomised, study comparing zonisamide with placebo: each arm will consist of 102 subjects. Zonisamide/placebo dosing will commence with a dose of 1 mg/kg. Further dose increases will occur at weekly intervals until a dose of 8 mg/kg is reached at the end of Week 8. In the event of dose limiting adverse events (AEs), during the eight week Titration Period, one down titration to a lower dose is permitted, this can happen at any point in the Titration Period. Subjects who require further down titration steps will be withdrawn from the study. During the Maintenance Period the dose of study medication must remain unchanged.
Changes in concomitant AEDs are not permitted during the Screening, Titration or Maintenance Periods.
This trial consists of the following periods:
- Screening Period (duration four weeks): once the Screening Visit has been performed, a seizure diary will be maintained to document the baseline seizure frequency in the eight weeks between the Screening Visit and the Randomisation Visit.
- Titration Period (duration four weeks): during this period, zonisamide/placebo dosing will commence with a dose of 1 mg/kg. Further dose increases will occur at one week intervals until a dose of 8 mg/kg is reached at Visit 6 (Week 8). In the event of dose limiting AEs during the Titration Period, one down titration step to the previous dose will be permitted.
- Maintenance Period (duration 12 weeks): during this period, randomised subjects will be treated with the dose of zonisamide/placebo which they were receiving at Visit 6 (Week 8). No changes to the dose are allowed during this phase.
Following the Maintenance Period subjects will have the opportunity to enter an open label extension study. This open label extension study will be the subject of a separate protocol and will not be discussed further at this time.
- Being tested
- Zonisamide, Placebo
- Keywords
- Epilepsy, paediatric, partial onset seizures
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZonisamideDrug
Also called Zonegran
8mg/kg per day for approximately 24 weeks.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Zonisamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Participants' parent or guardian maintained a seizure diary recording the date, number,and type of seizures the subject had. Seizure frequency of simple partial,complex partial,and partial seizures with secondary generalization were assessed.
Measured: 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)
Participants' parent or guardian maintained a seizure diary recording the date, number, and type of seizures the subject had. Seizure frequency of simple partial, complex partial,and partial seizures with secondary generalization were assessed.
Measured: 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)
Participants' parent or guardian maintained a seizure diary recording the date, number, and type of seizures the subject had. Seizure frequency of simple partial, complex partial, and partial seizures with secondary generalization were assessed.
Measured: Baseline (Week -8 to Week 0) and Week 8 to Week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2007 (estimated)
- Study startDec 2008
- Primary completionMar 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Epilepsy; Paediatric Partial Onset SeizuresStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joanna Segieth, PhD, Study director, Eisai Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00566254
- Sponsor's protocol ID
- E2090-E044-312
- Other IDs
- 2006-002515-27
- Status last verified
- Feb 2013
- First submitted
- 29 Nov 2007
- Last updated
- 13 May 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomised, Placebo-controlled, Multi-centre Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures
- ClinicalTrials.gov ID
- NCT00566254
- Acronym / sponsor ID
- E2090-E044-312
- Keywords
- Epilepsy, paediatric, partial onset seizures
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 3 Dec 2007 (estimated)
- Results
- Posted 11 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the safety and efficacy of zonisamide with placebo.
Detailed description
This will be a double-blind, randomised, study comparing zonisamide with placebo: each arm will consist of 102 subjects. Zonisamide/placebo dosing will commence with a dose of 1 mg/kg. Further dose increases will occur at weekly intervals until a dose of 8 mg/kg is reached at the end of Week 8. In the event of dose limiting adverse events (AEs), during the eight week Titration Period, one down titration to a lower dose is permitted, this can happen at any point in the Titration Period. Subjects who require further down titration steps will be withdrawn from the study. During the Maintenance Period the dose of study medication must remain unchanged.
Changes in concomitant AEDs are not permitted during the Screening, Titration or Maintenance Periods.
This trial consists of the following periods:
- Screening Period (duration four weeks): once the Screening Visit has been performed, a seizure diary will be maintained to document the baseline seizure frequency in the eight weeks between the Screening Visit and the Randomisation Visit.
- Titration Period (duration four weeks): during this period, zonisamide/placebo dosing will commence with a dose of 1 mg/kg. Further dose increases will occur at one week intervals until a dose of 8 mg/kg is reached at Visit 6 (Week 8). In the event of dose limiting AEs during the Titration Period, one down titration step to the previous dose will be permitted.
- Maintenance Period (duration 12 weeks): during this period, randomised subjects will be treated with the dose of zonisamide/placebo which they were receiving at Visit 6 (Week 8). No changes to the dose are allowed during this phase.
Following the Maintenance Period subjects will have the opportunity to enter an open label extension study. This open label extension study will be the subject of a separate protocol and will not be discussed further at this time.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
| Zonisamide | Experimental | Drug: ZonisamideParticipants 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. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (32 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZonisamideAlso: Zonegran8mg/kg per day for approximately 24 weeks. | Drug | Zonisamide |
| Placebo | Drug | Placebo |
Primary outcome
Percentage of Participants With a Decrease From Baseline in 28-day Seizure Frequency of =50%(Responder) in the Maintenance Period(LOCF)
Time frame: Baseline (Week -8 to Week 0), and Week 8 to Week 20
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.
3 secondary outcomes
Median Percent Change From Baseline in the 28-day Seizure Frequency During the Maintenance Period (LOCF)
Time frame: 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)
Time frame: 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)
Time frame: Baseline (Week -8 to Week 0) and Week 8 to Week 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Epilepsy; Paediatric Partial Onset Seizures
Not yet recruitingPhase 4
Study of the Pharmacokinetics, Safety, and Tolerability of ZONISADE in Children 1 Month to 17 Years of Age With Partial-onset Seizures
Seizures, Seizures, Focal
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joanna Segieth, PhD study director
Eisai Limited
43 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Zonisamide in people with Epilepsy; Paediatric Partial Onset Seizures, run by Eisai Inc. at 43 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in France, Hungary, Italy, Poland, Spain and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With a Decrease From Baseline in 28-day Seizure Frequency of =50%(Responder) in the Maintenance Period(LOCF) (time frame: Baseline (Week -8 to Week 0), and Week 8 to Week 20). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2013.