Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000096358
Ethics application status
Approved
Date submitted
13/02/2008
Date registered
20/02/2008
Date last updated
21/11/2008
Type of registration
Prospectively registered

Titles & IDs
Public title
A double blind, randomised, placebo-controlled, mulitcentre study to assess the efficacy and safety of adjunctive zonisamide in primary generalised tonic clonic seizures.
Scientific title
Efficacy and safety of adjuntice zonisamide in primary generalised tonic clonic seizures
Secondary ID [1] 521 0
E2090- E044-315
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
epilepsy 2564 0
Condition category
Condition code
Neurological 2666 2666 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
adjunctive therapy - Zonisamide. Patients will take study drug (either Zonisamide or placebo) alongside their usual Antiepileptic drug's. Patient's will commence on a dose of 1mg/kg (subjects<12 years or 50mg (subjects >12 years). Further dose increases will occur at one week intervals until a dose of 5mg/kg or 300mg is reached by week 4. Patients will then maintain their dose for futher 12 weeks.
Intervention code [1] 2296 0
Treatment: Drugs
Comparator / control treatment
Placebo will be the comparator to Zonisamide. Placebo will be dispensed in the same way as Zonisamide.
Control group
Placebo

Outcomes
Primary outcome [1] 3574 0
decrease of seizure frequency
Timepoint [1] 3574 0
after 16 weeks of active therapy
Secondary outcome [1] 5990 0
safety - blood samples will be taken and assessed for safety laboratory values.
Timepoint [1] 5990 0
At screening and final visit (after 16 weeks of active therapy)

Eligibility
Key inclusion criteria
primary generalized tonic clonic seizures
Minimum age
6 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
any other type of epilepsy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects will be enrolled and allocated to a treatment using a central randomisation system by phone.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will be randomised using a central randomisation system which will determine the sequence of patients.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
20/02/2008
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] 565 0
3050,
Recruitment postcode(s) [2] 760 0
3084
Recruitment postcode(s) [3] 761 0
2031
Recruitment postcode(s) [4] 762 0
2067
Recruitment postcode(s) [5] 763 0
3065
Recruitment outside Australia
Country [1] 667 0
Germany
State/province [1] 667 0
Country [2] 668 0
Finland
State/province [2] 668 0
Country [3] 669 0
Lithuania
State/province [3] 669 0
Country [4] 670 0
Czech Republic
State/province [4] 670 0
Country [5] 671 0
Hungary
State/province [5] 671 0
Country [6] 672 0
Estonia
State/province [6] 672 0
Country [7] 673 0
Russian Federation
State/province [7] 673 0
Country [8] 674 0
Ukraine
State/province [8] 674 0
Country [9] 675 0
Serbia and Montenegro
State/province [9] 675 0
Country [10] 676 0
Romania
State/province [10] 676 0
Country [11] 677 0
Croatia
State/province [11] 677 0
Country [12] 678 0
Croatia
State/province [12] 678 0
Country [13] 679 0
Poland
State/province [13] 679 0
Country [14] 680 0
Spain
State/province [14] 680 0

Funding & Sponsors
Funding source category [1] 3025 0
Commercial sector/Industry
Name [1] 3025 0
Eisai Global Clinical Development, Eisia Ltd.
Country [1] 3025 0
United Kingdom
Primary sponsor type
Commercial sector/Industry
Name
Eisia G.C.D., Eisai Ltd.
Address
3 Shortlands, London, W6 8EE, UK
Country
United Kingdom
Secondary sponsor category [1] 2731 0
Other Collaborative groups
Name [1] 2731 0
Parexel International Limited
Address [1] 2731 0
The Quays
101-105 Oxford Road, Uxbridge, Middlesex, UB8 1LZ
Country [1] 2731 0
United Kingdom
Secondary sponsor category [2] 2732 0
Other Collaborative groups
Name [2] 2732 0
Parexel International Limited
Address [2] 2732 0
3 Thomas Holt Drive
North Ryde
NSW 2113
Country [2] 2732 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4981 0
Royal Melbourne Human Research Ethics Committee
Ethics committee address [1] 4981 0
Ward 6 East, Research Directorate
Gratten St
Parkville
VIC 3050
Ethics committee country [1] 4981 0
Australia
Date submitted for ethics approval [1] 4981 0
21/11/2007
Approval date [1] 4981 0
20/02/2008
Ethics approval number [1] 4981 0
2007-287
Ethics committee name [2] 4982 0
Northern Sydney Central Coast Human Research Ethics Committee
Ethics committee address [2] 4982 0
Research Office, RNSH
Level 4
Vindin House,
Pacific Highway, St Leonards
NSW 2065
Ethics committee country [2] 4982 0
Australia
Date submitted for ethics approval [2] 4982 0
10/01/2008
Approval date [2] 4982 0
Ethics approval number [2] 4982 0
08/HARBR/7/8
Ethics committee name [3] 4983 0
Austin Health Human Research Ethics Committee
Ethics committee address [3] 4983 0
Level 8, Room 8322
Harold Stokes Building
Austin Hospital
145 Studley Road
Heidelberg
Victoria
3084
Ethics committee country [3] 4983 0
Australia
Date submitted for ethics approval [3] 4983 0
16/01/2008
Approval date [3] 4983 0
04/06/2008
Ethics approval number [3] 4983 0
H2008/03171
Ethics committee name [4] 5004 0
St Vincents Hospital (melbourne) Human Research Ethics Committee
Ethics committee address [4] 5004 0
Level 5, Aikenhead Building
27 Victoria Parade
Fitzroy
VIC 3065
Ethics committee country [4] 5004 0
Australia
Date submitted for ethics approval [4] 5004 0
31/01/2008
Approval date [4] 5004 0
Ethics approval number [4] 5004 0
014/08

Summary
Brief summary
This study is designed to compare how safe and effective zonisamide is compared to placebo in people with primary generalised tonic clonic seizures who are already being treated with one or two other anti-epileptic drugs. Zonisamide is an investigational drug.
Primary Research Objective: To assess the efficacy of adjunctive zonisamide in IGE in reducing the frequency of tonic-clonic seizures in subjects with continuing continuing primary generalised tonic-clonic seizures
Secondary Research Objective: To assess the safety and tolerability of adjunctive zonisamide.
Exploratory Research Objective: To further explore the efficacy of zonisamide on other seizure types expected to occur in a significant proportion of subjects (myoclonic seizures, absence seizures).
This is a double-blind, randomised, placebo-controlled study comparing zonisamide and placebo in 154 subjects (1:1 ratio). The study consists of Baseline, Titration and Maintenance periods.

Baseline Period - once the Screening Visit has been performed, a seizure diary will be maintained to document the baseline seizure frequency in the eight weeks before the Randomisation Visit.

Titration Period - zonisamide/placebo dose will commence at 1 mg/kg in subjects <12 years of age or at 50 mg for subjects 12 years of age. Further dose increases will occur at one week intervals until at dose of 5 mg/kg or 300 mg is reached by Week 4. If adverse events (AEs) occur, one titration step will be omitted during Weeks 0-3, in which case the dose reached at Week 4 will be 4 mg/kg or 250 mg. Subject's who require further down titration will be withdrawn from the study.

Maintenance Period - subjects will be treated with their Week 4 dose. In the event of seizures occurring in the first two weeks of the Maintenance Period, the dose will be increased to 6 mg/kg or 400 mg (or 5 mg/kg or 350 mg, if the subject omitted one dose in the Titration Period and the AE that led to this dose increase omission has subsided). The dose will be reduced to 4 mg/kg or 200 mg in dose-limiting AEs. Subjects who require further down titration or dose increases will be withdrawn (with the exception of those who had temporary dose decreases for not more that 4 days when necessitated by intercurrent illness). During the remainder of the Maintenance Period, the dose of study medication must remain unchanged.

During the entire study the patient will keep a seizure diary to ascertain seizure frequency and type. Adverse events (AEs) will be reviewed at every visit, also physical and neurological exams, orthostatic vitals, 12 lead ECGs and clinical labs will be collected at every visit.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28196 0
Address 28196 0
Country 28196 0
Phone 28196 0
Fax 28196 0
Email 28196 0
Contact person for public queries
Name 11353 0
Sophie Nzongani-Morin
Address 11353 0
190 Rue Championnet
PARIS, 75018
Country 11353 0
France
Phone 11353 0
+33 1 44 90-32 31
Fax 11353 0
Email 11353 0
[email protected]
Contact person for scientific queries
Name 2281 0
Janos Antal M.D.
Address 2281 0
Hermina utca 17.
Budapest, H-1146
Country 2281 0
Hungary
Phone 2281 0
36 1 461-7600
Fax 2281 0
Email 2281 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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