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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00692003




Registration number
NCT00692003
Ethics application status
Date submitted
3/06/2008
Date registered
6/06/2008
Date last updated
14/03/2017

Titles & IDs
Public title
Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
Scientific title
A Double-blind, Randomised, Placebo-controlled Multi-centre Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
Secondary ID [1] 0 0
Eudra ID #2007-003557-91.
Secondary ID [2] 0 0
E2090-E044-315
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zonisamide
Treatment: Drugs - Placebo

Active Comparator: Zonisamide -

Placebo Comparator: Placebo -


Treatment: Drugs: Zonisamide
25-400 mg capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) <12 years old: 1 mg/kg; >= 12 years old: 50 mg daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)

Treatment: Drugs: Placebo
25-400 mg Zonisamide Placebo capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) <12 years old: 1 mg/kg Zonisamide Placebo; >= 12 years old: 50 mg Zonisamide Placebo capsules daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Considered Responders as Assessed During the Maintenance Period - The number of participants who were considered responders during the 12 week Maintenance Period (Week 4 to Week 16). A responder was defined as a participant with a decrease from baseline in Primary Generalised Tonic-Clonic Seizures (PGTCS) frequency of >= 50% (i.e. 28-day PGTC seizure frequency in the period from Week 4 to the Week 16 visit compared to Week -8/-4 to randomization at Week 0). Each participant's response to treatment was assessed on the basis of their seizure diaries. The diary was dispensed at the Screening Visit and maintained by the participant (parent/caregiver) through out the titration and maintenance treatment periods until the Early termination Visit at Week 16. Due to early termination of the study by the Sponsor, no formal analyses were conducted.
Timepoint [1] 0 0
Baseline (Week -8/-4 to Week 0) and Maintenance Phase (Week 4 to Week 16)
Secondary outcome [1] 0 0
Absolute Change From Baseline in 28-day PGTC Seizure Frequency - Absolute Change from Baseline in 28-day PGTC Seizure Frequency was assessed both for the Maintenance Period alone (Week 4 to Week 16) and for the entire double-blind treatment period (Week 0 to Week 16). Due to early termination of the study by the Sponsor, no formal analyses were conducted.
Timepoint [1] 0 0
Baseline and up to 16 weeks

Eligibility
Key inclusion criteria
1. Subject is male or female and aged 6-65 years.

2. Subject has = 3 PGTCS over the two months before screening and during the eight weeks
Baseline Period with at least one seizure in each one month period. PGTCS must occur
in the context of Idiopathic Generalized Epilepsy (IGE) and may be accompanied by
other primary generalized seizures, provided these are also consistent with a
diagnosis of IGE.

3. Subject (or parent/caregiver, for subjects below the age of consent) is willing to
sign an informed consent form. For subjects below the age of consent in their country,
where appropriate they must be willing to give informed (written or verbal) assent.
Subjects from the age specified in local regulations will be required to sign an
appropriate informed consent form.

4. Subject is taking a stable regimen of one or two other Antiepileptic Drugs (AEDs) for
at least two weeks prior to Visit 1 (start of the Baseline Period).

5. Subject has a clinical diagnosis of any type of idiopathic generalized epilepsy which
has PGTCS (and which may be accompanied by other generalized seizure types), according
to the International League Against Epilepsy (ILAE) Classification of Epileptic
Seizures (1981) and the ILAE Classification of Epilepsies and Epileptic Syndromes
(1989). Diagnosis should have been established by clinical history,
electroencephalogram (EEG) and computed tomography/magnetic resonance imaging (CT/MRI)
of the brain consistent with idiopathic generalized epilepsy. CT/MRI scan should have
been performed within five years of the screening visit or, if not available from this
period, should be performed in the Baseline Period.

6. EEG should have been performed within one year of the screening visit or, if not
available from this period, should be performed in the Baseline Period.

7. Female subjects are pre-menarchal, or if of childbearing potential, are not pregnant
or lactating or are post-menopausal.

8. Female subjects of childbearing potential must abide by the one of the following
medically acceptable contraceptive measures: oral contraception pill, contraceptive
injections, implants or patches, intrauterine device in place for at least three
months or vasectomised partner or abstinence throughout the study.

9. Subject has a body weight = 20 kg.
Minimum age
6 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has progressive or focal neurological disease (as determined by pre-existing
brain imaging such as CT or MRI performed maximally five years before the screening
visit), or clinically significant organic disease.

2. Subject has a history of, or results of clinical investigations (including EEG data)
that are suggestive of, partial seizures as defined by the ILAE, including generalized
tonic clonic seizures which are suspected to be secondarily generalized.

3. Subjects with cryptogenic or symptomatic generalized epilepsy.

4. Subjects with psychogenic seizures.

5. Subject has a history of status epilepticus within a year of screening while complying
with AEDs.

6. Subject has seizures that only occur in clustered patterns.

7. Subject has a history of renal calculi or renal insufficiency (above the upper normal
limits of creatinine).

8. Subject has a known diagnosis of human immunodeficiency virus (HIV) or hepatitis B or
C.

9. Subject had a predisposing condition that might interfere with absorption,
distribution, or excretion of zonisamide.

10. Subject has a history of sensitivity to sulfonamide drugs or zonisamide and its
excipients.

11. Subject has a recent history of excessive alcohol use or drug abuse.

12. Subject has a history of suicide attempt in the five years before the screening
visit..

13. Subject has abnormal screening laboratory values that were clinically significant.

14. Subject has a history of demonstrated non-compliance with treatment or the subject or
parent/caregiver can be reasonably expected not to be compliant with study procedures
or to complete the study.

15. Subject has participated in a study of an investigational drug or device within 30
days prior to screening.

16. Subject has received previous treatment with zonisamide.

17. Subject is treated with ketogenic diet or vagus nerve stimulator.

18. Subject has a history of necessary treatment with rescue benzodiazepines which is
foreseen to continue during the study. Rescue benzodiazepines will not be allowed in
this study (stable dosing with a benzodiazepine as (one of the) baseline
anti-epileptic drug(s) is allowed).

19. Current psychosis or moderate to severe depression, or use of anti-psychotic drugs,
MAOIs, tricyclic antidepressants, benzodiazepine or barbiturate treatment for
disorders other than epilepsy, and stimulants (amphetamine derivatives) within 28 days
before the screening visit.

20. Concomitant use of acetazolamide, carbonic anhydrase inhibitors such as topiramate and
drugs with anticholinergic activity.

21. Concomitant use of felbamate or use of felbamate within two months prior to Visit 1.

22. Subject is not able to swallow capsules.

23. Subject is not in general good health as determined by medical history, physical exam
and screening laboratory results.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Strategic Health Evaluators Pty Ltd - Chatswood
Recruitment hospital [2] 0 0
The Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
Austin Health - Heidelburg
Recruitment hospital [4] 0 0
The Royal Melbourne Hospital - Melbourne
Recruitment hospital [5] 0 0
St. Vincents Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2067 - Chatswood
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
3084 - Heidelburg
Recruitment postcode(s) [4] 0 0
3050 - Melbourne
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Croatia
State/province [1] 0 0
HR
Country [2] 0 0
Czech Republic
State/province [2] 0 0
Hradec Kralove
Country [3] 0 0
Czech Republic
State/province [3] 0 0
Kromeriz
Country [4] 0 0
Czech Republic
State/province [4] 0 0
Olomouc
Country [5] 0 0
Czech Republic
State/province [5] 0 0
Ostrava
Country [6] 0 0
Czech Republic
State/province [6] 0 0
Plzen
Country [7] 0 0
Czech Republic
State/province [7] 0 0
Praha 5
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Rychnov nad Kneznou
Country [9] 0 0
Estonia
State/province [9] 0 0
Tallinn
Country [10] 0 0
Estonia
State/province [10] 0 0
Tartu
Country [11] 0 0
Finland
State/province [11] 0 0
SF
Country [12] 0 0
Finland
State/province [12] 0 0
Oulu
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Freiburg
Country [15] 0 0
Germany
State/province [15] 0 0
Marburg
Country [16] 0 0
Germany
State/province [16] 0 0
Munchen
Country [17] 0 0
Germany
State/province [17] 0 0
Ulm
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Hungary
State/province [19] 0 0
Gyula
Country [20] 0 0
Hungary
State/province [20] 0 0
Kecskemet
Country [21] 0 0
Hungary
State/province [21] 0 0
Szombathely
Country [22] 0 0
Hungary
State/province [22] 0 0
Veszpem
Country [23] 0 0
Lithuania
State/province [23] 0 0
Kaunas
Country [24] 0 0
Lithuania
State/province [24] 0 0
Vilnius
Country [25] 0 0
Poland
State/province [25] 0 0
Bialystok
Country [26] 0 0
Poland
State/province [26] 0 0
Gdansk
Country [27] 0 0
Poland
State/province [27] 0 0
Katowice
Country [28] 0 0
Poland
State/province [28] 0 0
Krakow
Country [29] 0 0
Poland
State/province [29] 0 0
Lodz
Country [30] 0 0
Poland
State/province [30] 0 0
Poznan
Country [31] 0 0
Romania
State/province [31] 0 0
Bucharest
Country [32] 0 0
Romania
State/province [32] 0 0
Cluj-Napoca
Country [33] 0 0
Romania
State/province [33] 0 0
Iasi
Country [34] 0 0
Romania
State/province [34] 0 0
Tg Mures
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Krasnoyarsk
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Moscow
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Novosibirsk
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Smolensk
Country [39] 0 0
Russian Federation
State/province [39] 0 0
St. Petersburg
Country [40] 0 0
Russian Federation
State/province [40] 0 0
St.Petersburg
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Yaroslavl
Country [42] 0 0
Serbia
State/province [42] 0 0
Belgrade
Country [43] 0 0
Serbia
State/province [43] 0 0
Kragujevac
Country [44] 0 0
Serbia
State/province [44] 0 0
Nis
Country [45] 0 0
Ukraine
State/province [45] 0 0
Dniepropetrovsk
Country [46] 0 0
Ukraine
State/province [46] 0 0
Kharkiv
Country [47] 0 0
Ukraine
State/province [47] 0 0
Kyiv
Country [48] 0 0
Ukraine
State/province [48] 0 0
Lviv
Country [49] 0 0
Ukraine
State/province [49] 0 0
Odesa
Country [50] 0 0
Ukraine
State/province [50] 0 0
Vinnitsa

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Zonisamide is already marketed for the treatment of partial seizures in epilepsy. This study
is intended to provide evidence that zonisamide is safe and effective in the treatment of
primary generalised tonic-clonic seizures. The total trial duration will be 5.5-6.5 months.
After that subjects who have completed the study will be eligible to enrol in an open-label
extension study until zonisamide is marketed for this indication or further development in
this indication stops. This extension study will be described in a separate protocol
(E2090-E044-316).
Trial website
https://clinicaltrials.gov/show/NCT00692003
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rob Van Maanen
Address 0 0
Eisai Limited
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00692003