Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate

NCT00713622 | Completed Phase 4

• 2 other identifiers: E2090-E044-4062007-005313-19
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Epilepsy

Keywords

Partial; onset; seizures

Outcome Measures

Primary Outcomes (1)

• Percent change from Baseline in 28-day seizure frequency at Week 12; response rate at 12 weeks.

  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.

  Visits 1 and Visit 8; vital signs and weight conducted at Visits 1,2,5 and 8; clinical laboratory tests Visit 1 and 8.

Study Arms (2)

1

ACTIVE COMPARATOR

Drug: Zonisamide

2

ACTIVE COMPARATOR

Drug: Sodium valproate

Interventions

Zonisamide DRUG

Capsules of 25mg, 50mg and 100mg zonisamide will be supplied. Dosing will be twice a day.

Also known as: Zonegran

1

Sodium valproate DRUG

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.

Also known as: Epilim

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Eisai Limited: lead

Study Sites (2)

Universitae Klinik fur Neurologiet

Innsbruck, 6020, Austria

Location

Kuopio University Hospital

Kuopio, 70211, Finland

Location

MeSH Terms

Conditions

Epilepsy; Seizures

Interventions

Zonisamide; Valproic Acid; Epilim

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Andrew Yeates

  Eisai Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2008
• First Posted: July 11, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: April 1, 2009
• Last Updated: November 3, 2015

Record last verified: 2015-11

Locations

AU (1); FI (1)