A Double-blind Study to Compare the Efficacy and Safety o... | NCT00477295

ID	Type	Description	Link
2006-000156-40	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Zonisamide	Active Comparator		Drug: Zonisamide
Carbamazepine	Active Comparator		Drug: Carbamazepine

Name	Type	Description	Arm Group Labels	Other Names
Zonisamide	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.

Measure	Description	Time Frame
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.	Week 31 through Week 109

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

INCLUSION CRITERIA:

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

Male or female subjects, 18 to 75 years of age inclusive.
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).
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).
Subjects have a documented electroencephalogram (EEG) within 12 months of the Screening Visit, compatible with localization-related epilepsy (to exclude primary generalized epilepsy).
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.
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.
Subjects who are able and willing to follow investigational study procedures, maintain a seizure diary, and report AEs.
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:

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).
Subjects with a history of absence, myoclonic, clonic, tonic, or atonic seizures.
Subjects have a history of status epilepticus, and/or non-epileptic seizures (e.g., metabolic, pseudo-seizures).
Subjects have experienced seizures relating to drugs, alcohol, acute medical illness, mental retardation, or subjects with situation-related seizures.
Subjects have progressive encephalopathy or findings consistent with progressive CNS disease or lesion (e.g. infection, demyelination, or tumour).
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.
Subjects have been previously treated with carbamazepine or zonisamide.
Subjects have received an investigational drug or device in the three months prior to the Screening Visit.
Subjects have a known hypersensitivity to sulfonamides, dibenzazepine derivatives, or tricyclic antidepressants.
Subjects have a history of bone marrow depression, low platelet count or other blood dyscrasia.
Subjects have a history of acute intermittent porphyria.
Subjects have a history of renal disorder (serum creatinine level of > 135 Ã¬mol / 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.
Subjects have a body weight of less than 40 kg.
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).
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.
Subjects are currently taking carbonic anhydrase inhibitors.
Subjects have a history of pancreatitis, nephrolithiasis or hypercalcuria, clinically significant laboratory or electro-cardiographic abnormalities, or uncontrolled hypertension.
Subjects are currently taking mono-amine oxidase inhibitors (MAOIs) or any other excluded medications.

Name	Affiliation	Role
Joanna Segieth	Eisai Limited	Study Director

PubMed Identifier	Type	Citation	Retractions
22683226	Derived	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.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP(the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
BG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Per Protocol Population: All randomized subjects who received at least one dose of study medication and who had no major protocol violations.

Posted

Number

Percentage of Participants

Week 31 through Week 109

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP(the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Units	Counts
Participants	OG000223 OG001233

Title

Denominators

Categories

Title	Measurements
	OG00079.4 OG00183.7

Secondary

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.

Per Protocol Population. N=number of subjects with evaluable data.

Posted

Number

Percentage of participants

Week 5 through Week 109

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP(the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Secondary

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.

Per Protocol Population

Posted

Median

Standard Error

Median Days

Week 1 through Week 109

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Secondary

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.

Per Protocol Population

Posted

Median

Standard Error

Median Days

Week 1 through Week 109

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Secondary

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.

Intent-to-Treat (ITT) Population - randomized subjects who received at least one dose of study medication.

Posted

Mean

Standard Deviation

Days

Week 5 through Week 83

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Secondary

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.

ITT Population

Posted

Mean

Standard Deviation

Days

Week 5 through Week 83

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Secondary

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.

Intent-to-Treat Population: All randomized subjects who received at least one dose of study medication. This was measured using Observed Case (OC).

Posted

Mean

Standard Deviation

Scores on a Scale

Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Secondary

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.

Intent-to-Treat Population. This was measured using Observed Case (OC).

Posted

Mean

Standard Deviation

Scores on a Scale

Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine

Secondary

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.

Intent-to-Treat Population. This was measured using Observed Case (OC).

Posted

Mean

Standard Deviation

Scores on a Scale

Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.

Secondary

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.

Intent-to-Treat Population. This was measured using Observed Case (OC).

Posted

Mean

Standard Deviation

Scores on a Scale

Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine

Secondary

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.

Intent-to-Treat Population. This was measured using Observed Case (OC). The percentages shown are calculated from the number of subjects at that visit with non-missing data for that score (n=174,196).

Posted

Number

Percentage of Participants

Week 31 through Week 83

ID	Title	Description
OG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
OG001	Carbamazepine

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Zonisamide	The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.			15	281	72	281
EG001	Carbamazepine	The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.			17	300	69	300

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Partial seizures with secondary generalization	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0014 affected300 at risk
Complex partial seizures	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Convulsion	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Epilepsy	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Ischemic stroke	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Partial seizures	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Subarachnoid hemorrahage	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0012 affected300 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Skull fracture	Injury, poisoning and procedural complications	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Appendicitis	Infections and infestations	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Chronic sinusitis	Infections and infestations	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Sinusitis bacterial	Infections and infestations	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Typhoid fever	Infections and infestations	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Acute psychosis	Psychiatric disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Suicidal ideation	Psychiatric disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Suicide attempt	Psychiatric disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0012 affected300 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Bradycardia	Cardiac disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Myocardial infarction	Cardiac disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Death	General disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Pyrexia	General disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Brain neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Rhinitis hypertrophic	Respiratory, thoracic and mediastinal disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Vertigo	Ear and labyrinth disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Hepatic enzyme increased	Investigations	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA v. 10.1	Systematic Assessment	EG0001 affected281 at risk EG0010 affected300 at risk
Hypotension	Vascular disorders	MedDRA v. 10.1	Systematic Assessment	EG0000 affected281 at risk EG0011 affected300 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Camperdown			Australia

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D013450	Sulfones
D013457	Sulfur Compounds
D007555	Isoxazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D003984	Dibenzazepines
D006575	Heterocyclic Compounds, 3-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
headache	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG00029 affected281 at risk EG00137 affected300 at risk
somnolence	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG00017 affected281 at risk EG00123 affected300 at risk
dizziness	Nervous system disorders	MedDRA v. 10.1	Systematic Assessment	EG00011 affected281 at risk EG00123 affected300 at risk
weight decreased	Investigations	MedDRA v. 10.1	Systematic Assessment	EG00019 affected281 at risk EG0010 affected300 at risk
decreased appetite	Metabolism and nutrition disorders	MedDRA v. 10.1	Systematic Assessment	EG00022 affected281 at risk EG0015 affected300 at risk