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

• ClinicalTrials.gov Identifier: NCT00477295
• Recruitment Status: Completed
• First Posted: May 23, 2007
• Results First Posted: February 8, 2013
• Last Update Posted: December 24, 2015
• Sponsor: Eisai Inc.
• Information provided by (Responsible Party): Eisai Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Epilepsy
• Interventions: Drug: Zonisamide; Drug: Carbamazepine
• Enrollment: 583

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description	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doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn.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.	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doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn.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.
Period Title: Overall Study
Started	282	301
Completed	161	192
Not Completed	121	109
Reason Not Completed
Adverse Event	31	35
Withdrawal by Subject	35	24
Lack of Efficacy	23	23
Protocol Violation	3	8
Physician Decision	4	5
Lost to Follow-up	21	11
Not specified	4	3

Baseline Characteristics

Arm/Group Title		Zonisamide	Carbamazepine	Total
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		281	300	581
Baseline Analysis Population Description		[Not Specified]
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	281 participants	300 participants	581 participants
		37.1 (16.33)	35.6 (15.50)	36.4 (15.91)
		[1] Measure Description: Safety Population.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	281 participants	300 participants	581 participants
	Female	107 38.1%	128 42.7%	235 40.4%
	Male	174 61.9%	172 57.3%	346 59.6%
		[1] Measure Description: Safety Population: All randomized subjects who received at least one dose of study medication.

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase
Description	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.
Time Frame	Week 31 through Week 109

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	223	233
Measure Type: Number; Unit of Measure: Percentage of Participants
	79.4	83.7

2. Secondary Outcome

Title	Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance Period
Description	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.
Time Frame	Week 5 through Week 109

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	216	229
Measure Type: Number; Unit of Measure: Percentage of participants
	67.6	74.7

3. Secondary Outcome

Title	Analysis of Time to Drop Out Due to an Adverse Event (AE)
Description	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.
Time Frame	Week 1 through Week 109

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	223	233
Median (Standard Error); Unit of Measure: Median Days
	NA [1] (NA)	NA [1] (NA)

[1]

Please note that this is reported as 'Not Calculable' due to insufficient events.

4. Secondary Outcome

Title	Analysis of Time to Drop Out Due to Lack of Efficacy
Description	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.
Time Frame	Week 1 through Week 109

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	223	233
Median (Standard Error); Unit of Measure: Median Days
	722 [1] (NA)	NA [1] (NA)

[1]

Please note that this is reported as 'Not Calculable' due to insufficient events.

5. Secondary Outcome

Title	Time to 6-months Seizure Freedom
Description	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.
Time Frame	Week 5 through Week 83

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	281	300
Mean (Standard Deviation); Unit of Measure: Days
	222.7 (49.78)	220.4 (46.31)

6. Secondary Outcome

Title	Time to 12-months Seizure Freedom
Description	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.
Time Frame	Week 5 through Week 83

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	281	300
Mean (Standard Deviation); Unit of Measure: Days
	399.3 (55.03)	395.6 (42.19)

7. Secondary Outcome

Title	Change From Baseline in Total ABNAS Score at Maintenance Period Visit 1
Description	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.
Time Frame	Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	281	300
Mean (Standard Deviation); Unit of Measure: Scores on a Scale
	1.6 (15.43)	-0.1 (12.71)

8. Secondary Outcome

Title	Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1
Description	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.
Time Frame	Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	281	300
Mean (Standard Deviation); Unit of Measure: Scores on a Scale
Anxiety	-2.036 (23.6120)	-1.993 (26.1087)
Sedation	-0.475 (21.7476)	-1.362 (18.0103)
Dysphoria	-1.930 (21.7585)	-3.833 (19.7824)

9. Secondary Outcome

Title	Change From Baseline in QOLIE-31-P Overall Score at Maintenance Period Visit 1
Description	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.
Time Frame	Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	281	300
Mean (Standard Deviation); Unit of Measure: Scores on a Scale
	4.474 (15.2838)	6.090 (13.2861)

10. Secondary Outcome

Title	Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1
Description	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.
Time Frame	Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	281	300
Mean (Standard Deviation); Unit of Measure: Scores on a Scale
Aggregate Mental Component Score	1.027 (10.9124)	2.495 (10.5310)
Aggregate Physical Component Score	1.895 (7.6287)	2.041 (6.2613)

11. Secondary Outcome

Title	Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1
Description	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.
Time Frame	Week 31 through Week 83

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description:	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.	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 Number of Participants Analyzed	174	196
Measure Type: Number; Unit of Measure: Percentage of Participants
Mobility: No problems	90.8	86.7
Mobility: Some problems	8.7	12.9
Mobility: Confined to Bed	0.5	0.5
Self-Care:No problems	96.7	97.6
Self-Care: Some problems	2.7	2.4
Self-Care: Unable to wash or dress	0.5	0.0
Usual Activities: No problems	89.1	84.8
Usual Activities: Some problems	9.8	15.2
Usual Activities: Unable to perform	1.1	0.0
Pain/Discomfort: None	75.5	73.2
Pain/Discomfort: Moderate	22.3	25.4
Pain/Discomfort: Extreme	2.2	1.4
Anxiety/Depression: None	64.3	62.9
Anxiety/Depression: Moderate	31.3	34.8
Anxiety/Depression: Extreme	4.4	2.4

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	For each AE category, a subject with two or more adverse events in that category is only counted once.
Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description	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.	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.
All-Cause Mortality
	Zonisamide	Carbamazepine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Zonisamide	Carbamazepine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	15/281 (5.34%)	17/300 (5.67%)
Cardiac disorders
Bradycardia † 1	0/281 (0.00%)	1/300 (0.33%)
Myocardial infarction † 1	1/281 (0.36%)	0/300 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	1/281 (0.36%)	0/300 (0.00%)
Gastrointestinal disorders
Gastric ulcer † 1	0/281 (0.00%)	1/300 (0.33%)
General disorders
Death † 1	1/281 (0.36%)	0/300 (0.00%)
Pyrexia † 1	1/281 (0.36%)	0/300 (0.00%)
Hepatobiliary disorders
Cholelithiasis † 1	0/281 (0.00%)	1/300 (0.33%)
Infections and infestations
Appendicitis † 1	1/281 (0.36%)	0/300 (0.00%)
Chronic sinusitis † 1	0/281 (0.00%)	1/300 (0.33%)
Sinusitis bacterial † 1	0/281 (0.00%)	1/300 (0.33%)
Typhoid fever † 1	1/281 (0.36%)	0/300 (0.00%)
Injury, poisoning and procedural complications
Facial bones fracture † 1	0/281 (0.00%)	2/300 (0.67%)
Femur fracture † 1	0/281 (0.00%)	1/300 (0.33%)
Head injury † 1	0/281 (0.00%)	1/300 (0.33%)
Humerus fracture † 1	0/281 (0.00%)	1/300 (0.33%)
Joint dislocation † 1	1/281 (0.36%)	0/300 (0.00%)
Muscle strain † 1	0/281 (0.00%)	1/300 (0.33%)
Radius fracture † 1	0/281 (0.00%)	1/300 (0.33%)
Skull fracture † 1	0/281 (0.00%)	1/300 (0.33%)
Investigations
Hepatic enzyme increased † 1	0/281 (0.00%)	1/300 (0.33%)
Metabolism and nutrition disorders
Hypokalemia † 1	1/281 (0.36%)	0/300 (0.00%)
Musculoskeletal and connective tissue disorders
Bone pain † 1	1/281 (0.36%)	0/300 (0.00%)
Musculoskeletal pain † 1	0/281 (0.00%)	1/300 (0.33%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm † 1	1/281 (0.36%)	0/300 (0.00%)
Prostate cancer † 1	0/281 (0.00%)	1/300 (0.33%)
Nervous system disorders
Partial seizures with secondary generalization † 1	0/281 (0.00%)	4/300 (1.33%)
Complex partial seizures † 1	1/281 (0.36%)	0/300 (0.00%)
Convulsion † 1	1/281 (0.36%)	0/300 (0.00%)
Epilepsy † 1	0/281 (0.00%)	1/300 (0.33%)
Ischemic stroke † 1	0/281 (0.00%)	1/300 (0.33%)
Partial seizures † 1	1/281 (0.36%)	0/300 (0.00%)
Subarachnoid hemorrahage † 1	0/281 (0.00%)	1/300 (0.33%)
Psychiatric disorders
Acute psychosis † 1	1/281 (0.36%)	0/300 (0.00%)
Suicidal ideation † 1	0/281 (0.00%)	1/300 (0.33%)
Suicide attempt † 1	0/281 (0.00%)	1/300 (0.33%)
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation † 1	0/281 (0.00%)	1/300 (0.33%)
Respiratory disorder † 1	1/281 (0.36%)	0/300 (0.00%)
Rhinitis hypertrophic † 1	0/281 (0.00%)	1/300 (0.33%)
Skin and subcutaneous tissue disorders
Rash † 1	0/281 (0.00%)	2/300 (0.67%)
Purpura † 1	1/281 (0.36%)	0/300 (0.00%)
Vascular disorders
Hypotension † 1	0/281 (0.00%)	1/300 (0.33%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA v. 10.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Zonisamide	Carbamazepine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	72/281 (25.62%)	69/300 (23.00%)
Investigations
weight decreased † 1	19/281 (6.76%)	0/300 (0.00%)
Metabolism and nutrition disorders
decreased appetite † 1	22/281 (7.83%)	5/300 (1.67%)
Nervous system disorders
headache † 1	29/281 (10.32%)	37/300 (12.33%)
somnolence † 1	17/281 (6.05%)	23/300 (7.67%)
dizziness † 1	11/281 (3.91%)	23/300 (7.67%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA v. 10.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Eisai Inc.
• Organization: Eisai Call Center
• Phone: 888-422-4743

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT00477295 History of Changes
• Other Study ID Numbers: E2090-E044-310; 2006-000156-40 ( EudraCT Number )
• First Submitted: May 21, 2007
• First Posted: May 23, 2007
• Results First Submitted: November 12, 2012
• Results First Posted: February 8, 2013
• Last Update Posted: December 24, 2015