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Perampanel Titration and Cognitive Effects

Primary Purpose

Epilepsy

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Perampanel 1 week titration

Perampanel 2 week titration

Perampanel 4mg

Placebo

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Perampanel, Cognition

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Stanford UniversityRecruiting
Northwestern University
New York University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

PER 1 Week Titration

PER 2 Week Titration

PER 4 mg

Arm Description

Participants will take 2mg placebo PO QD for six weeks.

Participants will take 2mg perampanel PO QD for one week, followed by 4mg perampanel PO QD for five weeks.

Participants will take 2mg perampanel PO QD for two weeks, followed by 4mg perampanel PO QD for four weeks.

Participants will take 4mg perampanel PO QD for six weeks

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT04417907

First Posted

June 2, 2020

Last Updated

February 4, 2023

Sponsor

Kimford Jay Meador

Collaborators

Eisai Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04417907

Brief Title

Perampanel Titration and Cognitive Effects

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 20, 2021 (Actual)

Primary Completion Date

September 30, 2023 (Anticipated)

Study Completion Date

September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Kimford Jay Meador

Collaborators

Eisai Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy

Keywords

Perampanel, Cognition

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

103 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will take 2mg placebo PO QD for six weeks.

Arm Title

PER 1 Week Titration

Arm Type

Experimental

Arm Description

Participants will take 2mg perampanel PO QD for one week, followed by 4mg perampanel PO QD for five weeks.

Arm Title

PER 2 Week Titration

Arm Type

Experimental

Arm Description

Participants will take 2mg perampanel PO QD for two weeks, followed by 4mg perampanel PO QD for four weeks.

Arm Title

PER 4 mg

Arm Type

Experimental

Arm Description

Participants will take 4mg perampanel PO QD for six weeks

Intervention Type

Drug

Intervention Name(s)

Perampanel 1 week titration

Other Intervention Name(s)

Fycompa

Intervention Description

Healthy adults will take 2mg perampanel PO QD for one week followed 4mg perampanel PO QD for five weeks.

Intervention Type

Drug

Intervention Name(s)

Perampanel 2 week titration

Other Intervention Name(s)

Fycompa

Intervention Description

Healthy adults will take 2mg perampanel PO QD for two weeks followed 4mg perampanel PO QD for four weeks.

Intervention Type

Drug

Intervention Name(s)

Perampanel 4mg

Other Intervention Name(s)

Fycompa

Intervention Description

Healthy adults will take 4mg perampanel PO QD for six weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Healthy adults will take 2mg placebo PO QD for six weeks

Primary Outcome Measure Information:

Title

Overall neuropsychological composite Z-score as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment.

Description

Time Frame

At the end of each week of treatment for 6 weeks plus a baseline measure for control.

Title

Composite Z-score of objective measures as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment.

Description

Time Frame

At the end of each week of treatment for 6 weeks plus a baseline measure for control.

Title

Composite Z-score of subjective measures as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment.

Description

Time Frame

At the end of each week of treatment for 6 weeks plus a baseline measure for control.

Secondary Outcome Measure Information:

Title

Description

Time Frame

At the end of the 6 week maintenance period plus a baseline measure for comparison.

Title

Description

Time Frame

At the end of the 6 week maintenance period plus a baseline measure for comparison.

Title

Description

Time Frame

At the end of the 6 week maintenance period plus a baseline measure for comparison.

Title

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.

Description

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.

Time Frame

At the end of each week of treatment for 6 weeks.

Title

Dropouts across the six-week treatment period measure of direct comparison of the 4 titration conditions across 6 weeks of treatment.

Description

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.

Time Frame

At the end of each week of treatment for 6 weeks.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jordan Seliger

Phone

650-460-9260

jseliger@stanford.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kimford Meador, MD

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jordan Seliger, MA

Phone

650-460-9260

jseliger@stanford.edu

First Name & Middle Initial & Last Name & Degree

Kimford Meador, MD

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Elizabeth Bachman, MPH

elizabeth.bachman@nm.org

First Name & Middle Initial & Last Name & Degree

Elizabeth Gerard, MD

Facility Name

New York University

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Samantha Martin, MA

samantha.martin@nyulangone.org

First Name & Middle Initial & Last Name & Degree

Beth Leeman-Markowski, MD

12. IPD Sharing Statement

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Perampanel Titration and Cognitive Effects

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