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

Phase 4

Completed

Conditions: Epilepsy

Interventions: Drug: Carbamazepine
Drug: Eslicarbazepine

Registration Number: NCT02912364

Lead Sponsor: Stanford University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Carbamazepine	Carbamazepine	Randomized to carbamazepine 400mg po bid in crossover design.
Eslicarbazepine	Eslicarbazepine	Randomized to eslicarbazepine 800mg po bid in crossover design.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.