Perampanel Titration and Cognitive Effects

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04417907
• Other study ID #: 54358
• Status: Terminated
• Phase: Phase 4
• Start date: October 20, 2021
• Est. completion date: May 1, 2023

Study information

• Verified date: May 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: May 1, 2023
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy adults between the ages of 18 and 55 years

2. Male or female (using approved birth control methods)

3. Informed consent obtained

Exclusion Criteria:

1. Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic, neurologic, psychiatric, or renal disease.

2. Presence or history of drug or alcohol abuse or positive urine drug test at screening.

3. 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).

4. Prior adverse reaction to or prior hypersensitivity to perampanel.

5. Prior participation in studies involving perampanel.

6. Subjects who have received any investigational drug within the previous thirty days.

7. Subjects with IQ < 80 as determined by the Peabody Picture Vocabulary Test after enrollment.

8. Positive pregnancy test. Women of childbearing potential will be required to use approved birth control methods during the study.

9. 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.

10. 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.

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Perampanel 1 week titration
Healthy adults will take 2mg perampanel PO QD for one week followed 4mg perampanel PO QD for five weeks.
• Perampanel 2 week titration
Healthy adults will take 2mg perampanel PO QD for two weeks followed 4mg perampanel PO QD for four weeks.
• Perampanel 4mg
Healthy adults will take 4mg perampanel PO QD for six weeks
• Placebo
Healthy adults will take 2mg placebo PO QD for six weeks

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	New York University	New York	New York
United States	Stanford University	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Kimford Jay Meador	Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. Various measures were combined collectively (averaged) to compute an overall Z-score for each group at each time point. These included: 1) Executive Function Score of computerized test battery; 2) Processing Speed Score of computerized test battery; 3) AEP total score; 4) POMS total and domain scores; 5) Three cognitive components of the QOLIE-31 (attention, memory, language). 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.
Primary	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.
Primary	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. Various measures were combined collectively (averaged) to compute an overall Z-score for each group at each time point. These included: 1) AEP total score; 2) POMS total and domain scores; 3) Three cognitive components of the QOLIE-31 (attention, memory, language). 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.
Secondary	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.
Secondary	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.