Trial Outcomes & Findings for A Double-blind Study to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy (NCT NCT00477295)

Last Updated: 2015-12-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

583 participants

Primary outcome timeframe

Week 31 through Week 109

Results posted on

2015-12-24

Participant Flow

Participant milestones

Participant milestones
Measure	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doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn.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.	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doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn.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.
Overall Study STARTED	282	301
Overall Study COMPLETED	161	192
Overall Study NOT COMPLETED	121	109

Reasons for withdrawal

Reasons for withdrawal
Measure	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doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn.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.	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.
Overall Study Adverse Event	31	35
Overall Study Withdrawal by Subject	35	24
Overall Study Lack of Efficacy	23	23
Overall Study Protocol Violation	3	8
Overall Study Physician Decision	4	5
Overall Study Lost to Follow-up	21	11
Overall Study Other	4	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zonisamide n=281 Participants 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.	Carbamazepine n=300 Participants 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.	Total n=581 Participants Total of all reporting groups
Age, Continuous	37.1 years STANDARD_DEVIATION 16.33 • n=5 Participants	35.6 years STANDARD_DEVIATION 15.50 • n=7 Participants	36.4 years STANDARD_DEVIATION 15.91 • n=5 Participants
Sex: Female, Male Female	107 Participants n=5 Participants	128 Participants n=7 Participants	235 Participants n=5 Participants
Sex: Female, Male Male	174 Participants n=5 Participants	172 Participants n=7 Participants	346 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 31 through Week 109

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

Outcome measures

Outcome measures
Measure	Zonisamide n=223 Participants 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.	Carbamazepine n=233 Participants 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.
Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase	79.4 Percentage of Participants	83.7 Percentage of Participants

SECONDARY outcome

Timeframe: Week 5 through Week 109

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

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=216 Participants 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.	Carbamazepine n=229 Participants 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.
Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance Period	67.6 Percentage of participants	74.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 1 through Week 109

Population: Per Protocol Population

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=223 Participants 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.	Carbamazepine n=233 Participants 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.
Analysis of Time to Drop Out Due to an Adverse Event (AE)	NA Median Days Standard Error NA Please note that this is reported as 'Not Calculable' due to insufficient events.	NA Median Days Standard Error NA Please note that this is reported as 'Not Calculable' due to insufficient events.

SECONDARY outcome

Timeframe: Week 1 through Week 109

Population: Per Protocol Population

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=223 Participants 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.	Carbamazepine n=233 Participants 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.
Analysis of Time to Drop Out Due to Lack of Efficacy	722 Median Days Standard Error NA Please note that this is reported as 'Not Calculable' due to insufficient events.	NA Median Days Standard Error NA Please note that this is reported as 'Not Calculable' due to insufficient events.

SECONDARY outcome

Timeframe: Week 5 through Week 83

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

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=281 Participants 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.	Carbamazepine n=300 Participants 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.
Time to 6-months Seizure Freedom	222.7 Days Standard Deviation 49.78	220.4 Days Standard Deviation 46.31

SECONDARY outcome

Timeframe: Week 5 through Week 83

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=281 Participants 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.	Carbamazepine n=300 Participants 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.
Time to 12-months Seizure Freedom	399.3 Days Standard Deviation 55.03	395.6 Days Standard Deviation 42.19

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=281 Participants 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.	Carbamazepine n=300 Participants 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.
Change From Baseline in Total ABNAS Score at Maintenance Period Visit 1	1.6 Scores on a Scale Standard Deviation 15.43	-0.1 Scores on a Scale Standard Deviation 12.71

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=281 Participants 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.	Carbamazepine n=300 Participants 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.
Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 Anxiety	-2.036 Scores on a Scale Standard Deviation 23.6120	-1.993 Scores on a Scale Standard Deviation 26.1087
Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 Sedation	-0.475 Scores on a Scale Standard Deviation 21.7476	-1.362 Scores on a Scale Standard Deviation 18.0103
Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 Dysphoria	-1.930 Scores on a Scale Standard Deviation 21.7585	-3.833 Scores on a Scale Standard Deviation 19.7824

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=281 Participants 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.	Carbamazepine n=300 Participants 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.
Change From Baseline in QOLIE-31-P Overall Score at Maintenance Period Visit 1	4.474 Scores on a Scale Standard Deviation 15.2838	6.090 Scores on a Scale Standard Deviation 13.2861

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=281 Participants 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.	Carbamazepine n=300 Participants 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.
Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1 Aggregate Mental Component Score	1.027 Scores on a Scale Standard Deviation 10.9124	2.495 Scores on a Scale Standard Deviation 10.5310
Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1 Aggregate Physical Component Score	1.895 Scores on a Scale Standard Deviation 7.6287	2.041 Scores on a Scale Standard Deviation 6.2613

SECONDARY outcome

Timeframe: Week 31 through Week 83

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=174 Participants 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.	Carbamazepine n=196 Participants 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.
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Mobility: No problems	90.8 Percentage of Participants	86.7 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Self-Care: Unable to wash or dress	0.5 Percentage of Participants	0.0 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Usual Activities: No problems	89.1 Percentage of Participants	84.8 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Pain/Discomfort: None	75.5 Percentage of Participants	73.2 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Pain/Discomfort: Moderate	22.3 Percentage of Participants	25.4 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Mobility: Some problems	8.7 Percentage of Participants	12.9 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Mobility: Confined to Bed	0.5 Percentage of Participants	0.5 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Self-Care:No problems	96.7 Percentage of Participants	97.6 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Self-Care: Some problems	2.7 Percentage of Participants	2.4 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Usual Activities: Some problems	9.8 Percentage of Participants	15.2 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Usual Activities: Unable to perform	1.1 Percentage of Participants	0.0 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Pain/Discomfort: Extreme	2.2 Percentage of Participants	1.4 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Anxiety/Depression: None	64.3 Percentage of Participants	62.9 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Anxiety/Depression: Moderate	31.3 Percentage of Participants	34.8 Percentage of Participants
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 Anxiety/Depression: Extreme	4.4 Percentage of Participants	2.4 Percentage of Participants

Adverse Events

Zonisamide

Serious events: 15 serious events

Other events: 72 other events

Deaths: 0 deaths

Carbamazepine

Serious events: 17 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Zonisamide n=281 participants at risk 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.	Carbamazepine n=300 participants at risk 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.
Nervous system disorders headache	10.3% 29/281 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.	12.3% 37/300 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.
Nervous system disorders somnolence	6.0% 17/281 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.	7.7% 23/300 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.
Nervous system disorders dizziness	3.9% 11/281 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.	7.7% 23/300 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.
Investigations weight decreased	6.8% 19/281 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.	0.00% 0/300 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.
Metabolism and nutrition disorders decreased appetite	7.8% 22/281 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.	1.7% 5/300 • A Treatment-Emergent Adverse Event (TEAE) is an Adverse Event (AE) with a start date on or after Day 1 and within 15 days of last dose, including AEs with missing start dates, for up to 116 weeks. For each AE category, a subject with two or more adverse events in that category is only counted once.

Additional Information

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Principal investigator is a sponsor employee
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