Comparison of the Cognitive and Behavioral Effects of Eslicarbazepine Acetate and Carbamazepine in Healthy Adults

Study Overview
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Brief Summary
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Double-blind, randomized, two period crossover comparison of the cognitive and behavioral effects of Eslicarbazepine acetate and Carbamazepine in healthy volunteers.

Detailed Description
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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.

Official Title
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Double-Blind, Randomized, Two Period Crossover Comparison of the Cognitive and Behavioral Effects of Eslicarbazepine Acetate and Carbamazepine in Healthy Adults

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Eslicarbazepine
* Drug: Carbamazepine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults between the ages of 18 and 55 years old. Male or female Exclusion Criteria: Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic, neurologic, psychiatric, or renal disease or pregnancy. Presence or history of drug or alcohol abuse. 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). Use of oral contraceptive hormones or other medications that could be affected by ESL or Carbamazepine. Prior adverse reaction to or prior hypersensitivity to either study medication or to related compounds. Prior participation in studies involving anticonvulsant medications. Subjects who have received any investigational drug within the previous thirty days. Subjects with IQ < 70 as determined by the Peabody Picture Vocabulary Test. Presence of HLA B*1502 in subjects of Asian descent; this will be obtained at screening in subjects of Asian descent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eslicarbazepine<br>Randomized to eslicarbazepine 800mg po bid in crossover design. | Drug: Eslicarbazepine<br>* 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.<br>* Other names: Aptiom;|
| Experimental: Carbamazepine<br>Randomized to carbamazepine 400mg po bid in crossover design. | Drug: Carbamazepine<br>* 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.<br>* Other names: Tegretol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At the end of each 6-week drug treatment period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At the end of each 6-week drug treatment period. | 
| 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. | Prior to treatment (non-drug condition average) and at the end of each six-week treatment period. | 
| 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. | Prior to treatment (non-drug condition average) and at the end of each six-week treatment period. | 
| 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. | Prior to treatment (non-drug condition average) and at the end of each six-week treatment period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eslicarbazepine, Carbamazepine, cognition