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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
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)
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
Timepoint [3] 0 0
Week 1 through Week 109
Secondary outcome [4] 0 0
Time to 6-months Seizure Freedom
Timepoint [4] 0 0
Week 5 through Week 83
Secondary outcome [5] 0 0
Time to 12-months Seizure Freedom
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
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
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
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
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
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
Sex
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
1/05/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2011
Sample size
Target
Accrual to date
Final
583
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
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Katowice
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Poland
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Krakow
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Poland
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Lodz
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Poland
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Lublin
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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/study/NCT00477295
Trial related presentations / publications
Baulac M, Brodie MJ, Patten A, Segieth J, Giorgi L. Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol. 2012 Jul;11(7):579-88. doi: 10.1016/S1474-4422(12)70105-9. Epub 2012 Jun 8.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00477295