Perampanel Titration and Cognitive Effects

Study Overview
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Brief Summary
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The objective of this study is to determine whether there are any differences in the cognitive abilities and/or behavioral response of normal healthy volunteers across different titration rates of perampanel.

Detailed Description
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This is a randomized, double-blind, parallel group design across different titration rates of perampanel in healthy volunteers. The study consists of 8 visits, 4 of which will occur at the participant's home, over a 7-week period. One hundred and three (103) normal healthy subjects will be treated with perampanel (PER) at one of four different titration rates: (1) 2mg/day PER for one week followed by 4mg/day PER for five weeks, (2) 2mg/day PER for two weeks followed by 4mg/day PER for four weeks, (3) 4mg/day PER for six weeks, or (4) placebo (0mg/day PER) for six weeks. Cognitive and behavioral function testing along with safety testing will be conducted at screening, pretreatment baseline, the end of each week during the titration and maintenance period.

Official Title
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Effects of Titration Rate on Cognitive and Behavioral Side Effects of Perampanel

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Perampanel 1 week titration
* Drug: Perampanel 2 week titration
* Drug: Perampanel 4mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults between the ages of 18 and 55 years Male or female (using approved birth control methods) Informed consent obtained Exclusion Criteria: Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic, neurologic, psychiatric, or renal disease. Presence or history of drug or alcohol abuse or positive urine drug test at screening. The use of concomitant medications, which are known to affect perampanel or the use of any concomitant medications that may alter cognitive function (see Section VIII.F for a partial list). Prior adverse reaction to or prior hypersensitivity to perampanel. Prior participation in studies involving perampanel. Subjects who have received any investigational drug within the previous thirty days. Subjects with IQ < 80 as determined by the Peabody Picture Vocabulary Test after enrollment. Positive pregnancy test. Women of childbearing potential will be required to use approved birth control methods during the study. Presence of lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the C-SSRS at Screening. Invalid results on computerized cognitive tests at screening as indicated by a 'No' on any of the validity indicators generated in the CNS Vital Signs report.

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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will take 2mg placebo PO QD for six weeks. | Drug: Placebo<br>* Healthy adults will take 2mg placebo PO QD for six weeks<br>|
| Experimental: PER 1 Week Titration<br>Participants will take 2mg perampanel PO QD for one week, followed by 4mg perampanel PO QD for five weeks. | Drug: Perampanel 1 week titration<br>* Healthy adults will take 2mg perampanel PO QD for one week followed 4mg perampanel PO QD for five weeks.<br>* Other names: Fycompa;|
| Experimental: PER 2 Week Titration<br>Participants will take 2mg perampanel PO QD for two weeks, followed by 4mg perampanel PO QD for four weeks. | Drug: Perampanel 2 week titration<br>* Healthy adults will take 2mg perampanel PO QD for two weeks followed 4mg perampanel PO QD for four weeks.<br>* Other names: Fycompa;|
| Experimental: PER 4 mg<br>Participants will take 4mg perampanel PO QD for six weeks | Drug: Perampanel 4mg<br>* Healthy adults will take 4mg perampanel PO QD for six weeks<br>* Other names: Fycompa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall neuropsychological composite Z-score as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment. | Z score of cognitive tests (selected performance measures from the computerized cognitive test battery) and questionnaires (AEP, POMS, QOLIE-cognitive questions) at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. 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 poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. | At the end of each week of treatment for 6 weeks plus a baseline measure for control. | 
| Composite Z-score of objective measures as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment. | Z score of objective cognitive tests (selected performance measures from the computerized cognitive test battery) at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. 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 poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. | At the end of each week of treatment for 6 weeks plus a baseline measure for control. | 
| Composite Z-score of subjective measures as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment. | Z score of subjective questionnaires (AEP, POMS, QOLIE-cognitive questions at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. 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 poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. | At the end of each week of treatment for 6 weeks plus a baseline measure for control. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall neuropsychological composite Z-score at the end of the maintenance period (study week 6) compared to baseline (study week 1) as a measure of direct comparison of change across the 4 titration conditions. | Z score of cognitive tests (selected performance measures from the computerized cognitive test battery), questionnaires (AEP, POMS, QOLIE-cognitive questions), and non-computerized cognitive scores (average of z-scores for MCG immediate, MCG delayed, SDMT, Stroop-average score) at the end of the maintenance period, compared to baseline measures collected prior to treatment. 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 poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. | At the end of the 6 week maintenance period plus a baseline measure for comparison. | 
| Overall cognitive composite Z-score at the end of the maintenance period (study week 6) compared to baseline (study week 1) as a measure of direct comparison of change across the 4 titration conditions. | Z score of cognitive tests (selected performance measures from the computerized cognitive test battery) and non-computerized cognitive scores (average of z-scores for MCG immediate, MCG delayed, SDMT, Stroop-average score) at the end of the maintenance period, compared to baseline measures collected prior to treatment. 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 poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. | At the end of the 6 week maintenance period plus a baseline measure for comparison. | 
| Overall behavioral composite Z-score at the end of the maintenance period (study week 6) compared to baseline (study week 1) as a measure of direct comparison of change across the 4 titration conditions. | Z score of behavioral tests and questionnaires (AEP, POMS, QOLIE-cognitive questions) at the end of the maintenance period, compared to baseline measures collected prior to treatment. 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 poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. | At the end of the 6 week maintenance period plus a baseline measure for comparison. | 
| Treatment Emergent Adverse Events (TEAEs) across the six-week treatment period measure of direct comparison of the 4 titration conditions across 6 weeks of treatment. | Number of TEAEs across the the four titration conditions over the six-week treatment period. A score of 0 indicates no TEAEs. Higher numbers indicate greater TEAEs. | At the end of each week of treatment for 6 weeks. | 
| Dropouts across the six-week treatment period measure of direct comparison of the 4 titration conditions across 6 weeks of treatment. | Number dropouts across the the four titration conditions over the six-week treatment period. A score of 0 indicates no dropouts. Higher numbers indicate greater dropouts. | At the end of each week of treatment for 6 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perampanel, Cognition