Please note that the ANZCTR website will be unavailable from 9am until 9.30am (AEST) on Monday 22nd July for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00477295




Registration number
NCT00477295
Ethics application status
Date submitted
21/05/2007
Date registered
23/05/2007
Date last updated
24/12/2015

Titles & IDs
Public title
A Double-blind Study to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy
Scientific title
A Randomized, Multi-centre, Double-blind Study, to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy
Secondary ID [1] 0 0
2006-000156-40
Secondary ID [2] 0 0
E2090-E044-310
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

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

Active Comparator: Zonisamide -

Active Comparator: Carbamazepine -


Treatment: Drugs: Zonisamide
Week 1 and 2 either 100mg zonisamide or 200 mg carbamazepine Week 3 and 4 either 200mg zonisamide or 4800 mg carbamazepine Week 5 and 6 either 300mg zonisamide or 600 mg carbamazepine; this dose then to be maintained unless a subject has a seizure more than two weeks post a dose increase.

Treatment: Drugs: Carbamazepine
Week 1 and 2 either 100mg zonisamide or 200 mg carbamazepine Week 3 and 4 either 200mg zonisamide or 4800 mg carbamazepine Week 5 and 6 either 300mg zonisamide or 600 mg carbamazepine; this dose then to be maintained unless a subject has a seizure more than two weeks post a dose increase.

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase - A subject achieved a 26-week seizure-free period if they were free of all seizures, regardless of seizure type, for 26 weeks while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.
Timepoint [1] 0 0
Week 31 through Week 109
Secondary outcome [1] 0 0
Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance Period - A subject achieved a 12-month seizure-free period if they were free of all seizures, regardless of seizure type, for 12 months while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.
Timepoint [1] 0 0
Week 5 through Week 109
Secondary outcome [2] 0 0
Analysis of Time to Drop Out Due to an Adverse Event (AE) - An AE is defined as any untoward medical occurrence in a subject and does not necessarily have a causal relationship with the medicinal product. Adverse events were identified by: any unfavorable or unintended sign, symptom or disease temporarily associated with the use of a medicinal product; any new disease or exacerbation of an existing disease; any deterioration in nonprotocol-required measurements of laboratory values or other clinical test; and recurrence of an intermittent medical condition not present at Baseline.
Timepoint [2] 0 0
Week 1 through Week 109
Secondary outcome [3] 0 0
Analysis of Time to Drop Out Due to Lack of Efficacy - Lack of efficacy was evaluated by the subject and on the basis of whether zonisamide and carbamazepine gave the subject at least a 26-week seizure free rate. The subject could withdraw at any time due to lack of efficacy.
Timepoint [3] 0 0
Week 1 through Week 109
Secondary outcome [4] 0 0
Time to 6-months Seizure Freedom - A subject achieved a 6-months seizure-free period if they were free of all seizures, regardless of seizure type, for 6-months while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.
Timepoint [4] 0 0
Week 5 through Week 83
Secondary outcome [5] 0 0
Time to 12-months Seizure Freedom - A subject achieved a 12-month seizure-free period if they were free of all seizures, regardless of seizure type, for 12-months while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.
Timepoint [5] 0 0
Week 5 through Week 83
Secondary outcome [6] 0 0
Change From Baseline in Total ABNAS Score at Maintenance Period Visit 1 - The Aldenkamp-Baker Neuropsychological Assessment Scale(ABNAS) is a subject based questionnaire to measure subjective perceived drug-related cognitive impairments. The ABNAS measured seven critical domains of cognition(tiredness/fatigue,hyperexcitability, slowing(mental and motor),memory impairment,attention disorders,impairment of motor coordination, and language disorders). The total score ranged from 0 to 72, with a higher score reflecting a high level of problems.
Timepoint [6] 0 0
Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)
Secondary outcome [7] 0 0
Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 - The Bond-Lader Visual Analogue Scale (VAS) is made up of 16 pairs of alternative descriptors of mood and attention at either end of a 10 cm line.
Subjects were asked to rate their feelings at the time of assessment by indicating the point on the line which best represent their mood. Each item was scored by measuring the position relative to the left hand end of the line and levels of anxiety, sedation, and dysphoria were then calculated from the combined scores of selected items. The scores ranged from 0 to 100, with a high score reflecting a high level of anxiety, sedation or dysphoria.
Timepoint [7] 0 0
Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)
Secondary outcome [8] 0 0
Change From Baseline in QOLIE-31-P Overall Score at Maintenance Period Visit 1 - The Quality of Life in Epilepsy - Problems(QOLIE-31-P) was completed by the patient and contained 30 items covering seven subscales(seizure worry, overall
Quality of Life (QOL),emotional well-being,energy-fatigue, cognition,medication effects and social function) and one item covering health status. It also included seven items addressing overall distress related to each subscale, an item addressing the relative importance of each subscale topic, and an item addressing perception of overall change in QOL at the end of the study. A high score reflects a good QOL. The following scale range is a sample of 1 of the 7 of the subscales:
10 (Best possible quality of life) - 0 (Worst possible quality of life);
Rand Corporation QOLIE-31 Scoring Manual was used. The QOLIE-31 overall score is calculated by summing the product of each scale score times its weight and summing overall all scales.
Timepoint [8] 0 0
Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)
Secondary outcome [9] 0 0
Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1 - The Short Form 36 Health and Well-Being Questionnaire (SF-36) is a 36-item generic health related QOL instrument covering the following domains: physical functioning, role-physical,bodily pain, general health, social functioning,role-emotional, mental health, and vitality. It yields a profile of eight scores, one for each domain, and physical and mental health summary measures. Each domain is described by a score ranging from 0 to 100, for a range of total possible scoes of 0-400 for physical and 0-400 for mental. An increase represents an improvement, whereas a decrease reflects a worsening.
Timepoint [9] 0 0
Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)
Secondary outcome [10] 0 0
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 - The European Quality of Life Group 5-Dimension Self-Report Questionnaire (EQ-5D) is a preference based generic health related quality of life (HRQoL) instrument which classifies health states across five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain has three levels, they are (1) no problems, (2) some problems, (3) extreme problems. The percentages shown are calculated from the number of subjects at that visit with non-missing data for that score.
Timepoint [10] 0 0
Week 31 through Week 83

Eligibility
Key inclusion criteria
INCLUSION CRITERIA:

Subjects will be eligible for the study if they meet all of the following inclusion
criteria:

1. Male or female subjects, 18 to 75 years of age inclusive.

2. Subjects with untreated, newly diagnosed epilepsy having at least two well documented,
unprovoked, clinically evaluated and classified partial seizures (with or without
secondary generalization) or generalized tonic-clonic seizures (without clear focal
origin) within 12 months of the Screening Visit, of which at least one seizure
occurred within three months of the Screening Visit (> one seizure within a 24 hour
period will be counted as one seizure).

3. Subjects will either have had no previous use of an AED, or treatment with one AED for
a maximum duration of two weeks before the Randomization Visit (T1).

4. Subjects have a documented electroencephalogram (EEG) within 12 months of the
Screening Visit, compatible with localization-related epilepsy (to exclude primary
generalized epilepsy).

5. Subjects have a documented computed axial tomography (CAT) scan or magnetic resonance
imaging (MRI) scan confirming the absence of a progressive neurological lesion within
12 months of the Screening Visit.

6. Female subjects without childbearing potential (two years post-menopausal, bilateral
oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects
with childbearing potential must not be pregnant as confirmed by a negative pregnancy
test at screening and randomization, must not be lactating and must be using a
medically acceptable form of contraception, for the duration of the study and for one
month following discontinuation of the study drug. Medically acceptable contraception
is defined here as oral contraception pill with at least 50 micrograms
ethinylestradiol per intake, contraceptive injections and implants, or intrauterine
device in place for at least three months.

7. Subjects who are able and willing to follow investigational study procedures, maintain
a seizure diary, and report AEs.

8. Subjects who are able and willing to give written informed consent.

EXCLUSION CRITERIA:

Subjects who meet any of the following exclusion criteria will not be eligible for the
study:

1. Subjects have a history of clinical investigations, including EEG data, that are
suggestive of idiopathic generalised epilepsy as defined by the International League
Against Epilepsy (ILAE).

2. Subjects with a history of absence, myoclonic, clonic, tonic, or atonic seizures.

3. Subjects have a history of status epilepticus, and/or non-epileptic seizures (e.g.,
metabolic, pseudo-seizures).

4. Subjects have experienced seizures relating to drugs, alcohol, acute medical illness,
mental retardation, or subjects with situation-related seizures.

5. Subjects have progressive encephalopathy or findings consistent with progressive CNS
disease or lesion (e.g. infection, demyelination, or tumour).

6. Subjects have a history of a significant or currently uncontrolled disease that will
interfere with the conduct of this study or the assessment of safety and efficacy of
the study drug.

7. Subjects have been previously treated with carbamazepine or zonisamide.

8. Subjects have received an investigational drug or device in the three months prior to
the Screening Visit.

9. Subjects have a known hypersensitivity to sulfonamides, dibenzazepine derivatives, or
tricyclic antidepressants.

10. Subjects have a history of bone marrow depression, low platelet count or other blood
dyscrasia.

11. Subjects have a history of acute intermittent porphyria.

12. Subjects have a history of renal disorder (serum creatinine level of > 135 ìmol / l
(1.5 mg/dL at the Screening Visit), hepatic disorder or clinically significant
abnormal liver function tests; aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) >2 times the upper normal limit.

13. Subjects have a body weight of less than 40 kg.

14. Subjects have a history of progressive malignancy within the previous 5 years
(excluding a history of non-metastasized and adequately treated cutaneous squamous
cell carcinoma).

15. Subjects have a history of psychiatric illness or mood disorder requiring
electro-convulsive or drug therapy within the previous 6 months which is considered
uncontrolled; a history of suicide attempt; alcohol or drug abuse; chronic treatment
with benzodiazepines or barbiturates.

16. Subjects are currently taking carbonic anhydrase inhibitors.

17. Subjects have a history of pancreatitis, nephrolithiasis or hypercalcuria, clinically
significant laboratory or electro-cardiographic abnormalities, or uncontrolled
hypertension.

18. Subjects are currently taking mono-amine oxidase inhibitors (MAOIs) or any other
excluded medications.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

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
Completed
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)
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Clayton
Recruitment hospital [3] 0 0
- Fitzroy
Recruitment hospital [4] 0 0
- Flinders
Recruitment hospital [5] 0 0
- Heidelberg West
Recruitment hospital [6] 0 0
- Parkville
Recruitment hospital [7] 0 0
- Queensland
Recruitment hospital [8] 0 0
- Wellington
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Fitzroy
Recruitment postcode(s) [4] 0 0
- Flinders
Recruitment postcode(s) [5] 0 0
- Heidelberg West
Recruitment postcode(s) [6] 0 0
- Parkville
Recruitment postcode(s) [7] 0 0
- Queensland
Recruitment postcode(s) [8] 0 0
- Wellington
Recruitment outside Australia
Country [1] 0 0
Denmark
State/province [1] 0 0
Aalborg
Country [2] 0 0
France
State/province [2] 0 0
Bethune cedex
Country [3] 0 0
France
State/province [3] 0 0
Dijon
Country [4] 0 0
France
State/province [4] 0 0
Paris
Country [5] 0 0
France
State/province [5] 0 0
St. Etienne
Country [6] 0 0
Germany
State/province [6] 0 0
Berlin
Country [7] 0 0
Germany
State/province [7] 0 0
Bochum
Country [8] 0 0
Germany
State/province [8] 0 0
Duesseldorf
Country [9] 0 0
Germany
State/province [9] 0 0
Munich
Country [10] 0 0
Germany
State/province [10] 0 0
Schwerin
Country [11] 0 0
Germany
State/province [11] 0 0
Westerstede
Country [12] 0 0
Greece
State/province [12] 0 0
Athens
Country [13] 0 0
Greece
State/province [13] 0 0
Thessaloniki
Country [14] 0 0
Hungary
State/province [14] 0 0
Budapest
Country [15] 0 0
Hungary
State/province [15] 0 0
Debrecen
Country [16] 0 0
Hungary
State/province [16] 0 0
Gyula
Country [17] 0 0
Hungary
State/province [17] 0 0
Hodmezovasarhely
Country [18] 0 0
Hungary
State/province [18] 0 0
Nyregyhaza
Country [19] 0 0
Hungary
State/province [19] 0 0
Zalaegerszeg-Pozva
Country [20] 0 0
India
State/province [20] 0 0
Bangalore
Country [21] 0 0
India
State/province [21] 0 0
Hyderabad
Country [22] 0 0
India
State/province [22] 0 0
Koturpuram
Country [23] 0 0
India
State/province [23] 0 0
Madurai
Country [24] 0 0
India
State/province [24] 0 0
New Delhi
Country [25] 0 0
India
State/province [25] 0 0
Pune
Country [26] 0 0
Italy
State/province [26] 0 0
Milan
Country [27] 0 0
Italy
State/province [27] 0 0
Monza
Country [28] 0 0
Italy
State/province [28] 0 0
Orbassano
Country [29] 0 0
Italy
State/province [29] 0 0
Rome
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Anyang
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seol
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Seoul
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Wonju
Country [34] 0 0
Poland
State/province [34] 0 0
Gdansk
Country [35] 0 0
Poland
State/province [35] 0 0
Katowice
Country [36] 0 0
Poland
State/province [36] 0 0
Krakow
Country [37] 0 0
Poland
State/province [37] 0 0
Lodz
Country [38] 0 0
Poland
State/province [38] 0 0
Lublin
Country [39] 0 0
Poland
State/province [39] 0 0
Poznan
Country [40] 0 0
Poland
State/province [40] 0 0
Sosnowiec
Country [41] 0 0
Poland
State/province [41] 0 0
Szcecin
Country [42] 0 0
Poland
State/province [42] 0 0
Warszawa
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Kaliningrad
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Kazan
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Moscow
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Saint Petersburg
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Yaroslavl
Country [48] 0 0
Serbia
State/province [48] 0 0
Belgrade
Country [49] 0 0
Serbia
State/province [49] 0 0
Nis
Country [50] 0 0
Serbia
State/province [50] 0 0
Novi Sad
Country [51] 0 0
Serbia
State/province [51] 0 0
Subotica
Country [52] 0 0
Slovakia
State/province [52] 0 0
Bratislava
Country [53] 0 0
Slovakia
State/province [53] 0 0
Bratslava
Country [54] 0 0
Slovakia
State/province [54] 0 0
Brezno
Country [55] 0 0
Slovakia
State/province [55] 0 0
Nove Zamky
Country [56] 0 0
Slovakia
State/province [56] 0 0
Vranov nad Toplou
Country [57] 0 0
Slovakia
State/province [57] 0 0
Zilina
Country [58] 0 0
South Africa
State/province [58] 0 0
Sandton
Country [59] 0 0
Spain
State/province [59] 0 0
Alicante
Country [60] 0 0
Spain
State/province [60] 0 0
Bacelona
Country [61] 0 0
Spain
State/province [61] 0 0
Barcelona
Country [62] 0 0
Spain
State/province [62] 0 0
Madrid
Country [63] 0 0
Spain
State/province [63] 0 0
Malaga
Country [64] 0 0
Spain
State/province [64] 0 0
Oviedo
Country [65] 0 0
Spain
State/province [65] 0 0
Sevilla
Country [66] 0 0
Sweden
State/province [66] 0 0
Goteborg
Country [67] 0 0
Sweden
State/province [67] 0 0
Lund
Country [68] 0 0
Taiwan
State/province [68] 0 0
Changhua
Country [69] 0 0
Taiwan
State/province [69] 0 0
Yong Kang
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Bristol
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Liverpool
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Treliske

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a two-arm, randomized, double-blind, non-inferiority study using a flexible dosing
regime to allow optimal zonisamide or carbamazepine therapy for individual subjects.
Assessment of eligibility will take place at the Screening Visit. The subjects will be
randomized to either the carbamazepine or zonisamide arm at the Randomization Visit (T1). T1
must occur as soon as possible (and at least within 14 days) of the Screening Visit in order
to optimize subject care.
Trial website
https://clinicaltrials.gov/show/NCT00477295
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joanna Segieth
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
Other publications