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Trial registered on ANZCTR


Registration number
ACTRN12608000516381
Ethics application status
Not yet submitted
Date submitted
19/09/2008
Date registered
2/10/2008
Date last updated
21/11/2008
Type of registration
Prospectively registered

Titles & IDs
Public title
Open label extension study following a double-blind, randomized, placebo-controlled, multicenter study to assess the efficacy and safety of adjunctive zonisamide in primary generalized tonic-clonic seizures.
Scientific title
Open label extension multicentere study to assess the efficacy and safety of adjunctive zonisamide in primary generalized tonic-clonic seizures.
Secondary ID [1] 720 0
Eisai study Number E2090-E044-316
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 3712 0
Condition category
Condition code
Neurological 3880 3880 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects who completed visit 7 of the double blind study (E2090-E044-315, Trial number ACTRN1260800009358) will be invited to enter this extension study. After provision of informed consent at this visit, the stubject will start with a double-blind Titration period (to avoid unblinding of study E2090-E044-315). Subjects treated with Zonisamide in study E2090-E044-315 will continue on the same dose of Zonisamide while they are being started with placebo. Subjects treated with placebo in study E2090-E044-315 will continue to take placebo and additionally be uptitrated with Zonisamide up to the dose level that subjects were treated with at the end of study E2090-E044-315 (up to a maximum of 400mg or 350mg (6mg/kg) if the subject is less than 12 years of age). For those subjects in the placebo group, dosing with Zonisamide will start with a dose of 1mg/kg (subjects <12 years) or 50mg (subjects>12 years). The dose of Zonisamide is uptitrated in the same schedule as in study E2090-E044-315. The titration period will last four to seven weeks. Subjects who completed the double blind study on a maximum tolerated dose of 200mg (or 4mg/kg for subjects <12 years) will complete titration more quickly than other subjects i.e within 3 weeks, but will be maintained on the week 3 dose for another week during the titration period in order to maintain the blind, before entering the open label maintenance Period. In subjects who did not tolerate this titration, both the blinded maintanence dose from study E2090-E044-315 abd the transition titration dose introduced in E2090-E044-316 will be down titrated to 100mg (if adult or child <12 years and weight >28kg) or 50mg (if child <12 and weight 20-28kg). When this dose is reached, open-label Zonisamide will be started at the age/weight appopriate starting dose, if this is decided to be in the best interest of the subject by the investigator. After this period subjects who completed the uptitration will be taking the maintanence dose of Zonisamide so the study will become in effect open label and a switch is made to open label maintanence medication. The dose of open-label zonisamide through the remainder of the study will be flexible at the discretion of the investigator and based on tolerability and efficacy. Open-label maintanence phase medication will continue until Zonisamide has been marketed. Trial medication, in the form of capsules, will be taken orally, once daily in the evening throughout the study. Patient's will continue to take their own antiepileptic drug throughout the study.
The open label study will continue until Zonisamide is marketed.
Intervention code [1] 3426 0
Treatment: Drugs
Comparator / control treatment
There is no control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 4782 0
to assess the long-term safety of zonisamide in subjects with Primary Generalised tonic clonic seizures. Safety will be measured by taking blood samples and recording of incidence of adverse and serios adverse events.
Timepoint [1] 4782 0
Blood samples will be taken every 6 months for the duration of the study. Adverse and serious adverse events will be recorded every 12 weeks for the duration of the study.
Secondary outcome [1] 8080 0
To assess long term maintenance of efficacy of using Zonisamide. This will be measured by using a diary to record the number of seizures a patient experiences and by changed to the patients, caregivers and physicians perception of the patient's condition.
Timepoint [1] 8080 0
Every 12 weeks a diary recording the number of seizures a patient experiences will be collected by the physician. The patient and caregiver will complete this diary.
Also every 12 weeks the patient, caregiver and Physician will complete a global impression of change questionnaire to record their perceptions of the patient's condition. The diary and questionnaire will be collected for the duration of the study.

Eligibility
Key inclusion criteria
Subject has completed the double blind study E2090-E044-315.
Subject has primary generalized tonic-clonic seizures.
Minimum age
6 Years
Maximum age
66 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
other types of seizures

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
16/01/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
154
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 1168 0
3050
Recruitment postcode(s) [2] 1169 0
3084
Recruitment postcode(s) [3] 1170 0
2031
Recruitment postcode(s) [4] 1171 0
2067
Recruitment postcode(s) [5] 1172 0
3065
Recruitment outside Australia
Country [1] 1202 0
Croatia
State/province [1] 1202 0
Country [2] 1203 0
Czech Republic
State/province [2] 1203 0
Country [3] 1204 0
Estonia
State/province [3] 1204 0
Country [4] 1205 0
Germany
State/province [4] 1205 0
Country [5] 1206 0
Hungary
State/province [5] 1206 0
Country [6] 1207 0
Lithuania
State/province [6] 1207 0
Country [7] 1208 0
Poland
State/province [7] 1208 0
Country [8] 1209 0
Serbia and Montenegro
State/province [8] 1209 0
Country [9] 1210 0
Russian Federation
State/province [9] 1210 0
Country [10] 1211 0
Ukraine
State/province [10] 1211 0
Country [11] 1212 0
Romania
State/province [11] 1212 0
Country [12] 1213 0
Spain
State/province [12] 1213 0

Funding & Sponsors
Funding source category [1] 3904 0
Commercial sector/Industry
Name [1] 3904 0
Eisai Ltd
Country [1] 3904 0
United Kingdom
Primary sponsor type
Commercial sector/Industry
Name
Eisai Ltd
Address
3 Shortlands
London
W6 8EE
Country
United Kingdom
Secondary sponsor category [1] 3503 0
Other
Name [1] 3503 0
Parexel International Limited
Address [1] 3503 0
The Quays
101-105 Oxford Road
Uxbridge
Middlesex
UB8 1LZ
Country [1] 3503 0
United Kingdom
Other collaborator category [1] 428 0
Other
Name [1] 428 0
Parexel International Pty Ltd
Address [1] 428 0
Level 6, 15 Talavera Road
North Ryde
NSW
2113
Country [1] 428 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 5960 0
Royal Melbourne Human Research Ethics Committee
Ethics committee address [1] 5960 0
Office for Research
Level 6 East,
Main Building, Grattan st
Parkville
VIC 3050
Ethics committee country [1] 5960 0
Australia
Date submitted for ethics approval [1] 5960 0
28/08/2008
Approval date [1] 5960 0
Ethics approval number [1] 5960 0
Ethics committee name [2] 5961 0
Northern Sydney Central Coast Human Research Ethics Committee
Ethics committee address [2] 5961 0
Research Office,
Royal North Shore Hospital,
Level 4, Vindin House
St Leonards
NSW
2065
Ethics committee country [2] 5961 0
Australia
Date submitted for ethics approval [2] 5961 0
16/10/2008
Approval date [2] 5961 0
Ethics approval number [2] 5961 0
Ethics committee name [3] 5962 0
Austin Health Human Research Ethics Committee
Ethics committee address [3] 5962 0
Research Ethics Unit (REU)
Level 8, Room 8322
Harold Stokes Building
Austin Hospital
145 Studley Road
Heidelberg
VIC 3084
Ethics committee country [3] 5962 0
Australia
Date submitted for ethics approval [3] 5962 0
15/10/2008
Approval date [3] 5962 0
Ethics approval number [3] 5962 0
Ethics committee name [4] 5963 0
St Vincents Hospital (melbourne) Human Research Ethics Committee
Ethics committee address [4] 5963 0
Level 5, Aikenhead Building
27 Victoria Parade
Fitzroy
VIC 3065
Ethics committee country [4] 5963 0
Australia
Date submitted for ethics approval [4] 5963 0
30/10/2008
Approval date [4] 5963 0
Ethics approval number [4] 5963 0

Summary
Brief summary
This study is an Open label extension study following a double-blind, randomized, placebo-controlled, multicenter study to assess the efficacy and safety of adjunctive zonisamide in primary generalized tonic-clonic seizures. Zonisamide is an investigational drug.
RESEARCH OBJECTIVES
To assess the long-term safety and efficacy of zonisamide in subjects with primary generalized tonic-clonic seizures.
STUDY DESIGN
Subjects who completed Visit 7 of the double blind study (E2090-E044-315) will be invited to enter into this extension study. After provision of informed consent at this visit, the study will start with a double-blind Titration Period (to avoid unblinding of study E2090-E044-315). Subjects treated with zonisamide in study E2090-E044-315 will continue on the same dose of zonisamide while they are being started with placebo. Subjects treated with placebo in study E2090-E044-315 will continue to take placebo and additionally be uptitrated with zonisamide up to the dose level that subjects were treated with at the end of study E2090-E044-315 (up to a maximum of 400 mg or 350 mg (6 mg/kg) if the subject is less than 12 years of age). For those subjects in the placebo group, dosing with zonisamide will start with a dose of 1 mg/kg (subjects < 12 years) or 50 mg (subjects = 12 years). The dose of zonisamide is up titrated in the same schedule as in study E2090-E044-315.
The Titration Period will last four to seven weeks. Subjects who completed the double blind study on a maximum tolerated dose of 200 mg (or 4 mg/kg for subjects <12 years) will complete titration more quickly than other subjects i.e within 3 weeks, but will be maintained on the Week 3 dose for another week during the Titration Period in order to maintain the blind, before entering the open label Maintenance Period. In subjects who do not tolerate this titration, both the blinded maintenance dose from study E2090-E044-315 and the transition titration dose introduced in E2090-E044-316 will be downtitrated to 100 mg (if adult or child < 12 years and weight >28 kg) or 50 mg (if child < 12 years and weight 20-28 kg). When this dose is reached, open-label zonisamide will be started at the age/weight-appropriate starting dose, if this is decided to be in the best interest of the subject by the investigator.

After this period subjects who completed the uptitration will be taking the maintenance dose of zonisamide so the study will become in effect open label and a switch is made to open-label maintenance medication. The dose of open-label zonisamide through the remainder of the study will be flexible at the discretion of the investigator and based on tolerability and efficacy.
Trial medication will be taken once daily in the evening throughout the study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28949 0
Address 28949 0
Country 28949 0
Phone 28949 0
Fax 28949 0
Email 28949 0
Contact person for public queries
Name 12106 0
Sophie Nzongani-Morin
Address 12106 0
Parexel International
190 Rue Championnet
Paris
75018
Country 12106 0
France
Phone 12106 0
+33 1 44 90 32 31
Fax 12106 0
Email 12106 0
[email protected]
Contact person for scientific queries
Name 3034 0
Janos Antal
Address 3034 0
Hermina utca 17
Budapest
1146
Country 3034 0
Hungary
Phone 3034 0
+36 1 461 7600
Fax 3034 0
Email 3034 0
[email protected]

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No Supporting Document Provided



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