Epilepsy
Conditions
Keywords
Eslicarbazepine, Carbamazepine, cognition
Brief summary
Double-blind, randomized, two period crossover comparison of the cognitive and behavioral effects of Eslicarbazepine acetate and Carbamazepine in healthy volunteers.
Detailed description
This study is a double-blind, randomized, two period crossover design. The study consists of 6 visits over a 21 week period. Forty six (46) normal healthy subjects will be treated with both Eslicarbazepine acetate (ESL, 800 mg/day) and Carbamazepine (CBZ, 800mg/day) for 6 weeks and 3 days each (maintenance 4 weeks and taper 3 days). Each antiepileptic drug (AED) treatment period will be followed by a four day taper and washout period off AED for the remainder of the month. Cognitive and behavioral testing along with safety testing will be conducted at pretreatment baseline, the end of each randomization AED maintenance period, and after the final washout period.
Interventions
DRUGEslicarbazepine
Healthy adults will be titrated onto Eslicarbazepine Acetate (800mg daily) . After four weeks maintenance they will be tapered off and enter washout period, then crossed over to 2nd drug.
DRUGCarbamazepine
Healthy adults will be titrated onto Carbamazepine (400 mg bid). After four weeks maintenance they will be tapered off and enter washout period, then crossed over to 2nd drug.
Sponsors
Sumitomo Pharma America, Inc.
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adults between the ages of 18 and 55 years old. 2. Male or female
Exclusion criteria
1. Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic, neurologic, psychiatric, or renal disease or pregnancy. 2. Presence or history of drug or alcohol abuse. 3. The use of concomitant medications, which are known to affect ESL or Carbamazepine or the use of any concomitant medications that may alter cognitive function (see Section VII.E for a partial list). 4. Use of oral contraceptive hormones or other medications that could be affected by ESL or Carbamazepine. 5. Prior adverse reaction to or prior hypersensitivity to either study medication or to related compounds. 6. Prior participation in studies involving anticonvulsant medications. 7. Subjects who have received any investigational drug within the previous thirty days. 8. Subjects with IQ \< 70 as determined by the Peabody Picture Vocabulary Test. 9. Presence of HLA B\*1502 in subjects of Asian descent; this will be obtained at screening in subjects of Asian descent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Composite Z Score of Neuropsychological Battery as a Measure of Direct Comparison of the 2 Antiepileptic Drugs. | At the end of each 6-week drug treatment period. | Z score of cognitive tests at end of each 6-week drug treatment period for each intervention (i.e., Eslicarbazepine and Carbamazepine). The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poor cognitive performance compared to the mean and positive numbers represent higher cognitive performance compared to the mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Z-score for Executive Function. | At the end of each 6-week drug treatment period. | Executive function consists of a composite of measures from the computerized cognitive tests. The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poor cognitive performance compared to the mean and positive numbers represent higher cognitive performance compared to the mean. |
| MCG Paragraph Recall Scores. | Prior to treatment (non-drug condition average) and at the end of each six-week treatment period. | Participants were read a paragraph and were asked to recall content immediately following and twenty minutes after hearing the reading. MCG = Medical College of Georgia. Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period. Score range: 0 - 60, higher scores indicate better memory function. |
| Dual Task Percent of Time in Box. | Prior to treatment (non-drug condition average) and at the end of each six-week treatment period. | Participants were asked to use their computer mouse to keep the cursor inside a moving box on the computer screen while simultaneously responding with a button press when a number on the screen exceeded a certain value. Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period. |
| Profile of Mood States (POMS) Score. | Prior to treatment (non-drug condition average) and at the end of each six-week treatment period. | Participants were asked to rate the extent to which they feel a variety of emotions/feelings. The overall score is presented. Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period. Score range: -32 to 200. Lower scores correspond to better mood state. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants who received either Eslicarbazepine Acetate (800mg once daily), or Carbamazepine, 400mg twice daily. | 46 |
| Total | 46 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 38.0 years STANDARD_DEVIATION 12 |
| Education Level | 15.0 years STANDARD_DEVIATION 1.9 |
| IQ Estimate | 98.6 units on a scale STANDARD_DEVIATION 12.2 |
| Race/Ethnicity, Customized African American | 3 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 6 Participants |
| Race/Ethnicity, Customized White/Caucasian | 24 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 |
| other Total, other adverse events | 12 / 29 | 21 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 |
Outcome results
Primary
Overall Composite Z Score of Neuropsychological Battery as a Measure of Direct Comparison of the 2 Antiepileptic Drugs.
Z score of cognitive tests at end of each 6-week drug treatment period for each intervention (i.e., Eslicarbazepine and Carbamazepine). The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poor cognitive performance compared to the mean and positive numbers represent higher cognitive performance compared to the mean.
Time frame: At the end of each 6-week drug treatment period.
Population: Participants who completed the protocol are included in the analysis. That is, participants who completed both treatment arms (completed treatment 2 in the participant flow) are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eslicarbazepine | Overall Composite Z Score of Neuropsychological Battery as a Measure of Direct Comparison of the 2 Antiepileptic Drugs. | .001 Z-score | Standard Deviation 0.5 |
| Carbamazepine | Overall Composite Z Score of Neuropsychological Battery as a Measure of Direct Comparison of the 2 Antiepileptic Drugs. | -.23 Z-score | Standard Deviation 0.61 |
p-value: <0.00195% CI: [0.13, 0.34]t-test, 2 sided
Secondary
Dual Task Percent of Time in Box.
Participants were asked to use their computer mouse to keep the cursor inside a moving box on the computer screen while simultaneously responding with a button press when a number on the screen exceeded a certain value. Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period.
Time frame: Prior to treatment (non-drug condition average) and at the end of each six-week treatment period.
Population: Participants who completed the protocol are included in the analysis. That is, participants who completed both treatment arms (Eslicarbazepine and Carbamazepine) are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eslicarbazepine | Dual Task Percent of Time in Box. | 62 percentage of time in box | Standard Deviation 33 |
| Carbamazepine | Dual Task Percent of Time in Box. | 62 percentage of time in box | Standard Deviation 33 |
| Carbamazepine | Dual Task Percent of Time in Box. | 60 percentage of time in box | Standard Deviation 34 |
Secondary
MCG Paragraph Recall Scores.
Participants were read a paragraph and were asked to recall content immediately following and twenty minutes after hearing the reading. MCG = Medical College of Georgia. Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period. Score range: 0 - 60, higher scores indicate better memory function.
Time frame: Prior to treatment (non-drug condition average) and at the end of each six-week treatment period.
Population: Participants who completed the protocol are included in the analysis. That is, participants who completed both treatment arms (Eslicarbazepine and Carbamazepine) are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eslicarbazepine | MCG Paragraph Recall Scores. | Immediate Recall | 34 units on a scale | Standard Deviation 17 |
| Eslicarbazepine | MCG Paragraph Recall Scores. | Delayed Recall | 33 units on a scale | Standard Deviation 18 |
| Carbamazepine | MCG Paragraph Recall Scores. | Immediate Recall | 33 units on a scale | Standard Deviation 12 |
| Carbamazepine | MCG Paragraph Recall Scores. | Delayed Recall | 31 units on a scale | Standard Deviation 13 |
| Carbamazepine | MCG Paragraph Recall Scores. | Immediate Recall | 31 units on a scale | Standard Deviation 15 |
| Carbamazepine | MCG Paragraph Recall Scores. | Delayed Recall | 30 units on a scale | Standard Deviation 16 |
Secondary
Overall Z-score for Executive Function.
Executive function consists of a composite of measures from the computerized cognitive tests. The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poor cognitive performance compared to the mean and positive numbers represent higher cognitive performance compared to the mean.
Time frame: At the end of each 6-week drug treatment period.
Population: Participants who completed the protocol are included in the analysis. That is, participants who completed both treatment arms (Eslicarbazepine and Carbamazepine) are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eslicarbazepine | Overall Z-score for Executive Function. | .22 Z-score | Standard Deviation 0.53 |
| Carbamazepine | Overall Z-score for Executive Function. | -.32 Z-score | Standard Deviation 0.76 |
p-value: <0.00195% CI: [0.3, 0.79]t-test, 2 sided
Secondary
Profile of Mood States (POMS) Score.
Participants were asked to rate the extent to which they feel a variety of emotions/feelings. The overall score is presented. Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period. Score range: -32 to 200. Lower scores correspond to better mood state.
Time frame: Prior to treatment (non-drug condition average) and at the end of each six-week treatment period.
Population: Participants who completed the protocol are included in the analysis. That is, participants who completed both treatment arms (Eslicarbazepine and Carbamazepine) are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eslicarbazepine | Profile of Mood States (POMS) Score. | 8 units on a scale | Standard Deviation 25 |
| Carbamazepine | Profile of Mood States (POMS) Score. | 11 units on a scale | Standard Deviation 29 |
| Carbamazepine | Profile of Mood States (POMS) Score. | 15 units on a scale | Standard Deviation 32 |