Epilepsy
Conditions
Keywords
Epilepsy
Brief summary
This is a two-arm, randomized, double-blind, non-inferiority study using a flexible dosing regime to allow optimal zonisamide or carbamazepine therapy for individual subjects. Assessment of eligibility will take place at the Screening Visit. The subjects will be randomized to either the carbamazepine or zonisamide arm at the Randomization Visit (T1). T1 must occur as soon as possible (and at least within 14 days) of the Screening Visit in order to optimize subject care.
Interventions
DRUGZonisamide
Week 1 and 2 either 100mg zonisamide or 200 mg carbamazepine Week 3 and 4 either 200mg zonisamide or 4800 mg carbamazepine Week 5 and 6 either 300mg zonisamide or 600 mg carbamazepine; this dose then to be maintained unless a subject has a seizure more than two weeks post a dose increase.
DRUGCarbamazepine
Week 1 and 2 either 100mg zonisamide or 200 mg carbamazepine Week 3 and 4 either 200mg zonisamide or 4800 mg carbamazepine Week 5 and 6 either 300mg zonisamide or 600 mg carbamazepine; this dose then to be maintained unless a subject has a seizure more than two weeks post a dose increase.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Subjects will be eligible for the study if they meet all of the following inclusion criteria: 1. Male or female subjects, 18 to 75 years of age inclusive. 2. Subjects with untreated, newly diagnosed epilepsy having at least two well documented, unprovoked, clinically evaluated and classified partial seizures (with or without secondary generalization) or generalized tonic-clonic seizures (without clear focal origin) within 12 months of the Screening Visit, of which at least one seizure occurred within three months of the Screening Visit (\> one seizure within a 24 hour period will be counted as one seizure). 3. Subjects will either have had no previous use of an AED, or treatment with one AED for a maximum duration of two weeks before the Randomization Visit (T1). 4. Subjects have a documented electroencephalogram (EEG) within 12 months of the Screening Visit, compatible with localization-related epilepsy (to exclude primary generalized epilepsy). 5. Subjects have a documented computed axial tomography (CAT) scan or magnetic resonance imaging (MRI) scan confirming the absence of a progressive neurological lesion within 12 months of the Screening Visit. 6. Female subjects without childbearing potential (two years post-menopausal, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential must not be pregnant as confirmed by a negative pregnancy test at screening and randomization, must not be lactating and must be using a medically acceptable form of contraception, for the duration of the study and for one month following discontinuation of the study drug. Medically acceptable contraception is defined here as oral contraception pill with at least 50 micrograms ethinylestradiol per intake, contraceptive injections and implants, or intrauterine device in place for at least three months. 7. Subjects who are able and willing to follow investigational study procedures, maintain a seizure diary, and report AEs. 8. Subjects who are able and willing to give written informed consent.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase | Week 31 through Week 109 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of Time to Drop Out Due to an Adverse Event (AE) | Week 1 through Week 109 | 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. |
| Analysis of Time to Drop Out Due to Lack of Efficacy | Week 1 through Week 109 | 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 to 6-months Seizure Freedom | Week 5 through Week 83 | 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 to 12-months Seizure Freedom | Week 5 through Week 83 | 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. |
| Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance Period | Week 5 through Week 109 | 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. |
| Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 | Baseline and Maintenance Period Visit 1 (Week 31 to Week 83) | 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. |
| Change From Baseline in QOLIE-31-P Overall Score at Maintenance Period Visit 1 | Baseline and Maintenance Period Visit 1 (Week 31 to Week 83) | 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. |
| Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1 | Baseline and Maintenance Period Visit 1 (Week 31 to Week 83) | 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. |
| Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Week 31 through Week 83 | 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. |
| Change From Baseline in Total ABNAS Score at Maintenance Period Visit 1 | Baseline and Maintenance Period Visit 1 (Week 31 to Week 83) | 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. |
Countries
Australia, Denmark, France, Germany, Greece, Hungary, India, Italy, Poland, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 281 |
| 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. | 300 |
| Total | 581 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 31 | 35 |
| Overall Study | Lack of Efficacy | 23 | 23 |
| Overall Study | Lost to Follow-up | 21 | 11 |
| Overall Study | Other | 4 | 3 |
| Overall Study | Physician Decision | 4 | 5 |
| Overall Study | Protocol Violation | 3 | 8 |
| Overall Study | Withdrawal by Subject | 35 | 24 |
Baseline characteristics
| Characteristic | Zonisamide | Carbamazepine | Total |
|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 16.33 | 35.6 years STANDARD_DEVIATION 15.5 | 36.4 years STANDARD_DEVIATION 15.91 |
| Sex: Female, Male Female | 107 Participants | 128 Participants | 235 Participants |
| Sex: Female, Male Male | 174 Participants | 172 Participants | 346 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 72 / 281 | 69 / 300 |
| serious Total, serious adverse events | 15 / 281 | 17 / 300 |
Outcome results
Primary
Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase
A subject achieved a 26-week seizure-free period if they were free of all seizures, regardless of seizure type, for 26 weeks while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zonisamide | Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase | 79.4 Percentage of Participants |
| Carbamazepine | Percentage of Participants Who Experienced Seizure Freedom for 26-weeks During the Maintenance Phase | 83.7 Percentage of Participants |
Secondary
Analysis of Time to Drop Out Due to an Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a subject and does not necessarily have a causal relationship with the medicinal product. Adverse events were identified by: any unfavorable or unintended sign, symptom or disease temporarily associated with the use of a medicinal product; any new disease or exacerbation of an existing disease; any deterioration in nonprotocol-required measurements of laboratory values or other clinical test; and recurrence of an intermittent medical condition not present at Baseline.
Time frame: Week 1 through Week 109
Population: Per Protocol Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zonisamide | Analysis of Time to Drop Out Due to an Adverse Event (AE) | NA Median Days |
| Carbamazepine | Analysis of Time to Drop Out Due to an Adverse Event (AE) | NA Median Days |
Secondary
Analysis of Time to Drop Out Due to Lack of Efficacy
Lack of efficacy was evaluated by the subject and on the basis of whether zonisamide and carbamazepine gave the subject at least a 26-week seizure free rate. The subject could withdraw at any time due to lack of efficacy.
Time frame: Week 1 through Week 109
Population: Per Protocol Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Zonisamide | Analysis of Time to Drop Out Due to Lack of Efficacy | 722 Median Days |
| Carbamazepine | Analysis of Time to Drop Out Due to Lack of Efficacy | NA Median Days |
Secondary
Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1
The Bond-Lader Visual Analogue Scale (VAS) is made up of 16 pairs of alternative descriptors of mood and attention at either end of a 10 cm line. Subjects were asked to rate their feelings at the time of assessment by indicating the point on the line which best represent their mood. Each item was scored by measuring the position relative to the left hand end of the line and levels of anxiety, sedation, and dysphoria were then calculated from the combined scores of selected items. The scores ranged from 0 to 100, with a high score reflecting a high level of anxiety, sedation or dysphoria.
Time frame: Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)
Population: Intent-to-Treat Population. This was measured using Observed Case (OC).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zonisamide | 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 23.612 |
| Zonisamide | 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 |
| Zonisamide | 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 |
| Carbamazepine | Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 | Anxiety | -1.993 Scores on a Scale | Standard Deviation 26.1087 |
| Carbamazepine | Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 | Sedation | -1.362 Scores on a Scale | Standard Deviation 18.0103 |
| Carbamazepine | Change From Baseline in Bond and Lader VAS Mood Sub-Scores at Maintenance Period Visit 1 | Dysphoria | -3.833 Scores on a Scale | Standard Deviation 19.7824 |
Secondary
Change From Baseline in QOLIE-31-P Overall Score at Maintenance Period Visit 1
The Quality of Life in Epilepsy - Problems(QOLIE-31-P) was completed by the patient and contained 30 items covering seven subscales(seizure worry, overall Quality of Life (QOL),emotional well-being,energy-fatigue, cognition,medication effects and social function) and one item covering health status. It also included seven items addressing overall distress related to each subscale, an item addressing the relative importance of each subscale topic, and an item addressing perception of overall change in QOL at the end of the study. A high score reflects a good QOL. The following scale range is a sample of 1 of the 7 of the subscales: 10 (Best possible quality of life) - 0 (Worst possible quality of life); Rand Corporation QOLIE-31 Scoring Manual was used. The QOLIE-31 overall score is calculated by summing the product of each scale score times its weight and summing overall all scales.
Time frame: Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)
Population: Intent-to-Treat Population. This was measured using Observed Case (OC).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zonisamide | Change From Baseline in QOLIE-31-P Overall Score at Maintenance Period Visit 1 | 4.474 Scores on a Scale | Standard Deviation 15.2838 |
| Carbamazepine | Change From Baseline in QOLIE-31-P Overall Score at Maintenance Period Visit 1 | 6.090 Scores on a Scale | Standard Deviation 13.2861 |
Secondary
Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1
The Short Form 36 Health and Well-Being Questionnaire (SF-36) is a 36-item generic health related QOL instrument covering the following domains: physical functioning, role-physical,bodily pain, general health, social functioning,role-emotional, mental health, and vitality. It yields a profile of eight scores, one for each domain, and physical and mental health summary measures. Each domain is described by a score ranging from 0 to 100, for a range of total possible scoes of 0-400 for physical and 0-400 for mental. An increase represents an improvement, whereas a decrease reflects a worsening.
Time frame: Baseline and Maintenance Period Visit 1 (Week 31 to Week 83)
Population: Intent-to-Treat Population. This was measured using Observed Case (OC).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zonisamide | 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 |
| Zonisamide | 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 |
| Carbamazepine | Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1 | Aggregate Mental Component Score | 2.495 Scores on a Scale | Standard Deviation 10.531 |
| Carbamazepine | Change From Baseline in SF-36 Aggregate Mental and Physical Component Score at Maintenance Period Visit 1 | Aggregate Physical Component Score | 2.041 Scores on a Scale | Standard Deviation 6.2613 |
Secondary
Change From Baseline in Total ABNAS Score at Maintenance Period Visit 1
The Aldenkamp-Baker Neuropsychological Assessment Scale(ABNAS) is a subject based questionnaire to measure subjective perceived drug-related cognitive impairments. The ABNAS measured seven critical domains of cognition(tiredness/fatigue,hyperexcitability, slowing(mental and motor),memory impairment,attention disorders,impairment of motor coordination, and language disorders). The total score ranged from 0 to 72, with a higher score reflecting a high level of problems.
Time frame: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zonisamide | Change From Baseline in Total ABNAS Score at Maintenance Period Visit 1 | 1.6 Scores on a Scale | Standard Deviation 15.43 |
| Carbamazepine | Change From Baseline in Total ABNAS Score at Maintenance Period Visit 1 | -0.1 Scores on a Scale | Standard Deviation 12.71 |
Secondary
Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance Period
A subject achieved a 12-month seizure-free period if they were free of all seizures, regardless of seizure type, for 12 months while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.
Time frame: Week 5 through Week 109
Population: Per Protocol Population. N=number of subjects with evaluable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zonisamide | Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance Period | 67.6 Percentage of participants |
| Carbamazepine | Percentage of Participants Who Experienced Seizure Freedom for 12-months During the FDP and Maintenance Period | 74.7 Percentage of participants |
Secondary
Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1
The European Quality of Life Group 5-Dimension Self-Report Questionnaire (EQ-5D) is a preference based generic health related quality of life (HRQoL) instrument which classifies health states across five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain has three levels, they are (1) no problems, (2) some problems, (3) extreme problems. The percentages shown are calculated from the number of subjects at that visit with non-missing data for that score.
Time frame: 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).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Mobility: No problems | 90.8 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Mobility: Some problems | 8.7 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Mobility: Confined to Bed | 0.5 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Self-Care:No problems | 96.7 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Self-Care: Some problems | 2.7 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Usual Activities: No problems | 89.1 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Usual Activities: Some problems | 9.8 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Usual Activities: Unable to perform | 1.1 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Pain/Discomfort: None | 75.5 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Pain/Discomfort: Moderate | 22.3 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Pain/Discomfort: Extreme | 2.2 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Anxiety/Depression: None | 64.3 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Anxiety/Depression: Moderate | 31.3 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Anxiety/Depression: Extreme | 4.4 Percentage of Participants |
| Zonisamide | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Self-Care: Unable to wash or dress | 0.5 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Pain/Discomfort: None | 73.2 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Mobility: No problems | 86.7 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Self-Care: Some problems | 2.4 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Mobility: Some problems | 12.9 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Pain/Discomfort: Moderate | 25.4 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Anxiety/Depression: Extreme | 2.4 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Pain/Discomfort: Extreme | 1.4 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Self-Care: Unable to wash or dress | 0.0 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Mobility: Confined to Bed | 0.5 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Usual Activities: No problems | 84.8 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Anxiety/Depression: None | 62.9 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Usual Activities: Some problems | 15.2 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Self-Care:No problems | 97.6 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Usual Activities: Unable to perform | 0.0 Percentage of Participants |
| Carbamazepine | Percentage of Participants With EQ-5D Scores at Maintenance Period Visit 1 | Anxiety/Depression: Moderate | 34.8 Percentage of Participants |
Secondary
Time to 12-months Seizure Freedom
A subject achieved a 12-month seizure-free period if they were free of all seizures, regardless of seizure type, for 12-months while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.
Time frame: Week 5 through Week 83
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zonisamide | Time to 12-months Seizure Freedom | 399.3 Days | Standard Deviation 55.03 |
| Carbamazepine | Time to 12-months Seizure Freedom | 395.6 Days | Standard Deviation 42.19 |
Secondary
Time to 6-months Seizure Freedom
A subject achieved a 6-months seizure-free period if they were free of all seizures, regardless of seizure type, for 6-months while receiving the same dose. The occurrence of seizures was documented in the seizure diary, which was maintained by the subject and reviewed at each following visit.
Time frame: Week 5 through Week 83
Population: Intent-to-Treat (ITT) Population - randomized subjects who received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zonisamide | Time to 6-months Seizure Freedom | 222.7 Days | Standard Deviation 49.78 |
| Carbamazepine | Time to 6-months Seizure Freedom | 220.4 Days | Standard Deviation 46.31 |