EpilepsyPhase 4NCT00713622
Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
A Phase 4 study testing Zonisamide and Sodium valproate in people with Epilepsy, run by Eisai Limited at 2 sites in 2 countries.
Trial summary
Zonisamide (Zonegran) and sodium valproate (Epilim) are both medicines approved to treat epilepsy. The purpose of this study is to find out the extent to which zonisamide may affect memory and concentration, compared to sodium valproate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepsy
- What is being tested?
- Zonisamide and Sodium valproate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2008to Apr 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with a clinical diagnosis of non-symptomatic (i.e., idiopathic or cryptogenic) localisation-related epilepsy with partial onset seizures with or without secondary generalisation according to International League Against Epilepsy (ILAE) classification27. Diagnosis should be clinically established by history, by previous electroencephalogram (EEG) and by previous magnetic resonance imaging or computer tomography of the brain, consistent with localisation related epilepsy. No lower or upper limit of baseline seizures is defined.
- Able and willing to sign informed consent form (ICF) in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines.
- Male or female subjects aged ≥18 years.
- Subjects taking carbamazepine as monotherapy at baseline or who can be transferred to carbamazepine monotherapy in the two months before the Screening Visit. Dose of carbamazepine is within that recommended by the SPC. Carbamazepine dose has not been altered during the previous 2 weeks prior to the start of the Baseline Period, or 6 weeks if the Baseline Period is to be shortened due to the availability of a retrospective seizure history. The carbamazepine dose is to remain stable throughout the study.
- Subjects requiring addition of another AED, either because they continue to have seizures (are refractory), or because they wish eventually to switch to another AED for other reasons after the study completion (e.g. tolerability reasons).
- Female subjects of childbearing potential must not be pregnant (as confirmed by negative serum beta-human chorionic gonadotropin (βHCG) at screening and negative urine pregnancy test at baseline and during the study), must not be lactating and must use a medically acceptable form of contraception during the study and for at least 1 month after discontinuation of study drug. Medically acceptable contraception is defined here as:
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- High dose combined oral contraceptive (OC) pill (50µg of oestrogen preparation)
- Documented surgical sterilisation or documented vasectomised sexual partner
- Intrauterine device in place for at least 3 months and not exceeding the documented replacement date. (If the replacement date is not available, the device must not have been in situ for more than 5 years).
- Women more than 2 years post-menopause
- Abstinence Examples of contraception NOT acceptable include, but are not limited to:· Conventional dose of combined OC (< 50µg oestrogen)
- Progesterone-only OC
- Contraceptive implant
- Contraceptive patch
- Progesterone injection
- Barrier contraception:
- Condom
- Diaphragm
- Sponge
Who cannot join
- Previous treatment with valproate or zonisamide.
- Use of an AED other than carbamazepine less than 6 weeks prior to randomisation, and other than carbamazepine, zonisamide or sodium valproate during the study.
- Hypersensitivity to zonisamide or valproate or their respective excipients.
- Predisposing condition potentially altering the absorption, distribution or elimination of zonisamide or valproate.
- Sulphonamide allergy.
- Subjects with diagnosed idiopathic/primary generalised epilepsy or with results of clinical investigations or EEG that suggest idiopathic/primary generalised epilepsy.
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- History of status epilepticus within 12 months of screening whilst complying with AED therapy.
- History of cluster seizures.
- History of non epileptic seizures.
- Use of benzodiazepines during the Baseline Period or during randomised treatment.
- Regular treatment with antihistamines.
- Use of ketogenic diet.
- Use of acetazolamide, triamterene, vitamin C (>2g/day), regular antacids or other medicines associated with nephrolithiasis less than one month prior to randomisation or during the study.
- Subjects with a vagal nerve stimulator implanted, or due to be implanted within the expected duration of the study.
- Subjects expected to undergo any surgery within the expected duration of the study.
- History of renal calculi or renal insufficiency (above the upper normal limits of creatinine).
- Active psychiatric disease.
- History of suicide attempt within last 2 years.
- History of drug or alcohol abuse within the last 2 years.
- History of cerebrovascular disease/stroke or transient ischemic attacks; progressive neurological disease; focal central nervous system pathology or behavioural disturbances that may impair the subject's ability to complete the neuropsychological tests; or previous or current brain neoplasm.
- Neoplastic disease within the last 5 years except non-metastatic and adequately treated cutaneous squamous cell carcinoma.
- Diagnosis of human immunodeficiency virus (HIV) or Hepatitis B or C.
- Other clinically significant organic disease.
- Female subjects who are lactating, pregnant or intending to become pregnant.
- Subjects with history of demonstrated non compliance with medication or an inability to maintain a seizure diary.
- Subjects considered by the Investigator not to be within normal cognitive limits.
- Participation in clinical study within 30 days of screening.
- Clinically significant laboratory value abnormalities at baseline.
- Weight <40kg
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Multicentre, Randomised, Active Comparator, Parallel Group Study To Compare The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
Zonisamide (Zonegran) and sodium valproate (Epilim) are both medicines approved to treat epilepsy. The purpose of this study is to find out the extent to which zonisamide may affect memory and concentration, compared to sodium valproate.
Read the detailed description
Zonisamide (Zonegran) and sodium valproate (Epilim) are both medicines approved to treat epilepsy.
The purpose of this study is to find out the extent to which zonisamide may affect memory and concentration, compared to sodium valproate. This will be investigated using cognitive tests which are performed on a computer screen. Either zonisamide or sodium valproate will be added as a second medicine to the one patients are currently taking, carbamazepine (Tegretol), which will be continued throughout the study.
It is planned that about 80 people across Europe will take part in this study. For the purpose of the study, patients will need to go to the study doctor's clinic 4 times and have 5 telephone calls. Involvement in the study might be as long as 20 weeks, but it could be as short as 12 weeks. The length of the study and number of visits will depend on whether patients have an accurate recording of previous seizures already, how many seizures they have during the study, and whether they decide to continue or to stop treatment after the study is completed.
Adult subjects with a clinical diagnosis of non-symptomatic (i.e., idiopathic or unknown cause) localisation-related epilepsy, with partial onset seizures with or without secondary generalisation, who are receiving fixed dose carbamazepine as their only therapy or can be transferred to carbamazepine (as their only therapy) in the two months before the study baseline. Subjects must require addition of another anti-epileptic drug (AED) to their anti-epileptic therapy, either because they continue to have seizures (i.e., are not controlled), or because they wish to switch to another AED for other reasons (e.g., they tolerate another drug better).
- Conditions
- Epilepsy
- Being tested
- Zonisamide, Sodium valproate
- Keywords
- Partial, onset, seizures
- Medical subject headings
- Epilepsy, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZonisamideDrug
Also called Zonegran
Capsules of 25mg, 50mg and 100mg zonisamide will be supplied. Dosing will be twice a day.
Sodium valproateDrug
Also called Epilim
Crushable tablets of 100mg and enteric coated tablets of 200mg and 500mg will be supplied. Dosing will start at 600mg/day, increasing to the minimally effective dose, the maximum tolerated dose, or 2500mg/day, whichever is the lowest.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Not described Receives: Drug: Zonisamide |
| 2 | Active comparator | Not described Receives: Drug: Sodium valproate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change from Baseline in 28-day seizure frequency at Week 12; response rate at 12 weeks.
Measured: Change from baseline to Week 12 in the Computerised Visual Searching Task Reaction Time (CVST) from the Ferum Psyche (FePsy) cognitive battery, which measures central information processing speed conducted at visits 2, 5 and 8.
Secondary outcomes (1)
Safety will be assessed by the incidence of AEs and serious adverse events (SAEs); incidence of withdrawal for treatment emergent adverse events (TEAEs); physical and neurological examinations.
Measured: Visits 1 and Visit 8; vital signs and weight conducted at Visits 1,2,5 and 8; clinical laboratory tests Visit 1 and 8.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2008 (estimated)
- Study startJun 2008
- Primary completionDec 2008
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andrew Yeates, Study director, Eisai Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00713622
- Sponsor's protocol ID
- E2090-E044-406
- Other IDs
- 2007-005313-19
- Status last verified
- Nov 2015
- First submitted
- 8 Jul 2008
- Last updated
- 3 Nov 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Randomised, Active Comparator, Parallel Group Study To Compare The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
- ClinicalTrials.gov ID
- NCT00713622
- Acronym / sponsor ID
- E2090-E044-406
- Conditions
- Epilepsy
- Keywords
- Partial, onset, seizures
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Eisai LimitedIndustry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- Dec 2008 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 11 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Zonisamide (Zonegran) and sodium valproate (Epilim) are both medicines approved to treat epilepsy. The purpose of this study is to find out the extent to which zonisamide may affect memory and concentration, compared to sodium valproate.
Detailed description
Zonisamide (Zonegran) and sodium valproate (Epilim) are both medicines approved to treat epilepsy.
The purpose of this study is to find out the extent to which zonisamide may affect memory and concentration, compared to sodium valproate. This will be investigated using cognitive tests which are performed on a computer screen. Either zonisamide or sodium valproate will be added as a second medicine to the one patients are currently taking, carbamazepine (Tegretol), which will be continued throughout the study.
It is planned that about 80 people across Europe will take part in this study. For the purpose of the study, patients will need to go to the study doctor's clinic 4 times and have 5 telephone calls. Involvement in the study might be as long as 20 weeks, but it could be as short as 12 weeks. The length of the study and number of visits will depend on whether patients have an accurate recording of previous seizures already, how many seizures they have during the study, and whether they decide to continue or to stop treatment after the study is completed.
Adult subjects with a clinical diagnosis of non-symptomatic (i.e., idiopathic or unknown cause) localisation-related epilepsy, with partial onset seizures with or without secondary generalisation, who are receiving fixed dose carbamazepine as their only therapy or can be transferred to carbamazepine (as their only therapy) in the two months before the study baseline. Subjects must require addition of another anti-epileptic drug (AED) to their anti-epileptic therapy, either because they continue to have seizures (i.e., are not controlled), or because they wish to switch to another AED for other reasons (e.g., they tolerate another drug better).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Zonisamide |
| 2 | Active comparator | Drug: Sodium valproate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Subjects with a clinical diagnosis of non-symptomatic (i.e., idiopathic or cryptogenic) localisation-related epilepsy with partial onset seizures with or without secondary generalisation according to International League Against Epilepsy (ILAE) classification27. Diagnosis should be clinically established by history, by previous electroencephalogram (EEG) and by previous magnetic resonance imaging or computer tomography of the brain, consistent with localisation related epilepsy. No lower or upper limit of baseline seizures is defined.
- Able and willing to sign informed consent form (ICF) in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines.
- Male or female subjects aged ≥18 years.
- Subjects taking carbamazepine as monotherapy at baseline or who can be transferred to carbamazepine monotherapy in the two months before the Screening Visit. Dose of carbamazepine is within that recommended by the SPC. Carbamazepine dose has not been altered during the previous 2 weeks prior to the start of the Baseline Period, or 6 weeks if the Baseline Period is to be shortened due to the availability of a retrospective seizure history. The carbamazepine dose is to remain stable throughout the study.
- Subjects requiring addition of another AED, either because they continue to have seizures (are refractory), or because they wish eventually to switch to another AED for other reasons after the study completion (e.g. tolerability reasons).
Key exclusion criteria (29 listed)
- Previous treatment with valproate or zonisamide.
- Use of an AED other than carbamazepine less than 6 weeks prior to randomisation, and other than carbamazepine, zonisamide or sodium valproate during the study.
- Hypersensitivity to zonisamide or valproate or their respective excipients.
- Predisposing condition potentially altering the absorption, distribution or elimination of zonisamide or valproate.
- Sulphonamide allergy.
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: ZonegranCapsules of 25mg, 50mg and 100mg zonisamide will be supplied. Dosing will be twice a day. | Drug | 1 |
| Sodium valproateAlso: EpilimCrushable tablets of 100mg and enteric coated tablets of 200mg and 500mg will be supplied. Dosing will start at 600mg/day, increasing to the minimally effective dose, the maximum tolerated dose, or 2500mg/day, whichever is the lowest. | Drug | 2 |
Primary outcome
Percent change from Baseline in 28-day seizure frequency at Week 12; response rate at 12 weeks.
Time frame: Change from baseline to Week 12 in the Computerised Visual Searching Task Reaction Time (CVST) from the Ferum Psyche (FePsy) cognitive battery, which measures central information processing speed conducted at visits 2, 5 and 8.
1 secondary outcome
Safety will be assessed by the incidence of AEs and serious adverse events (SAEs); incidence of withdrawal for treatment emergent adverse events (TEAEs); physical and neurological examinations.
Time frame: Visits 1 and Visit 8; vital signs and weight conducted at Visits 1,2,5 and 8; clinical laboratory tests Visit 1 and 8.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2015.
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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.
Andrew Yeates study director
Eisai Limited
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zonisamide and Sodium valproate in people with Epilepsy, run by Eisai Limited at 2 sites in 2 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 19 inclusion and 29 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 3 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Austria, Finland. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percent change from Baseline in 28-day seizure frequency at Week 12; response rate at 12 weeks. (time frame: Change from baseline to Week 12 in the Computerised Visual Searching Task Reaction Time (CVST) from the Ferum Psyche (FePsy) cognitive battery, which measures central information processing speed conducted at visits 2, 5 and 8.). 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 3 Nov 2015.