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Trial record 24 of 83 for:    CARBAMAZEPINE AND Cytochrome P-450 CYP3A Inducers

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
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
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Zonisamide Carbamazepine
Hide 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doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn.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doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn.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
Arm/Group Title Zonisamide Carbamazepine Total
Hide 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
Hide 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.
1.Primary Outcome
Title Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Population. N=number of subjects with evaluable data.
Arm/Group Title Zonisamide Carbamazepine
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Population
Arm/Group Title Zonisamide Carbamazepine
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Population
Arm/Group Title Zonisamide Carbamazepine
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population - randomized subjects who received at least one dose of study medication.
Arm/Group Title Zonisamide Carbamazepine
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Zonisamide Carbamazepine
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. This was measured using Observed Case (OC).
Arm/Group Title Zonisamide Carbamazepine
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. This was measured using Observed Case (OC).
Arm/Group Title Zonisamide Carbamazepine
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. This was measured using Observed Case (OC).
Arm/Group Title Zonisamide Carbamazepine
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
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
Hide 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   --/--   --/-- 
Show Serious Adverse Events Hide 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
Show Other (Not Including Serious) Adverse Events Hide 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
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
Layout table for Results Point of Contact information
Name/Title: Eisai Inc.
Organization: Eisai Call Center
Phone: 888-422-4743
Layout table for additonal information
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