A Double-blind Study to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy

NCT ID: NCT00477295

Last Updated: 2015-12-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 583 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2011-01-31

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.

Conditions

Epilepsy

Keywords

Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Zonisamide

Group Type: ACTIVE_COMPARATOR

Zonisamide

Intervention Type: DRUG

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.

Carbamazepine

Group Type: ACTIVE_COMPARATOR

Carbamazepine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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 Type: DRUG

Other Intervention Names

Zonegran

Eligibility Criteria

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

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 Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joanna Segieth

Role: STUDY_DIRECTOR

Eisai Limited

Locations

Camperdown, , Australia

Clayton, , Australia

Fitzroy, , Australia

Flinders, , Australia

Heidelberg West, , Australia

Parkville, , Australia

Queensland, , Australia

Wellington, , Australia

Aalborg, , Denmark

Béthune, , France

Dijon, , France

Paris, , France

Saint-Etienne, , France

Berlin, , Germany

Bochum, , Germany

Düsseldorf, , Germany

Munich, , Germany

Schwerin, , Germany

Westerstede, , Germany

Athens, , Greece

Thessaloniki, , Greece

Budapest, , Hungary

Debrecen, , Hungary

Gyula, , Hungary

Hódmezővásárhely, , Hungary

Nyregyhaza, , Hungary

Zalaegerszeg-Pozva, , Hungary

Bangalore, , India

Hyderabad, , India

Koturpuram, , India

Madurai, , India

New Delhi, , India

Pune, , India

Milan, , Italy

Monza, , Italy

Orbassano, , Italy

Rome, , Italy

Gdansk, , Poland

Katowice, , Poland

Krakow, , Poland

Lodz, , Poland

Lublin, , Poland

Poznan, , Poland

Sosnowiec, , Poland

Szcecin, , Poland

Warsaw, , Poland

Kaliningrad, , Russia

Kazan', , Russia

Moscow, , Russia

Saint Petersburg, , Russia

Yaroslavl, , Russia

Belgrade, , Serbia

Niš, , Serbia

Novi Sad, , Serbia

Subotica, , Serbia

Bratislava, , Slovakia

Bratslava, , Slovakia

Brezno, , Slovakia

Nové Zámky, , Slovakia

Vranov nad Topľou, , Slovakia

Žilina, , Slovakia

Sandton, , South Africa

Anyang, , South Korea

Seoul, , South Korea

Wŏnju, , South Korea

Alicante, , Spain

Bacelona, , Spain

Barcelona, , Spain

Madrid, , Spain

Málaga, , Spain

Oviedo, , Spain

Seville, , Spain

Gothenburg, , Sweden

Lund, , Sweden

Changhua, , Taiwan

Yongkang District, , Taiwan

Bristol, , United Kingdom

Liverpool, , United Kingdom

Treliske, , United Kingdom

Countries

Australia; Denmark; France; Germany; Greece; Hungary; India; Italy; Poland; Russia; Serbia; Slovakia; South Africa; South Korea; Spain; Sweden; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 22683226 (View on PubMed)

Other Identifiers

2006-000156-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E2090-E044-310

Identifier Type: -

Identifier Source: org_study_id