Perampanel Titration and Cognitive Effects

NCT04417907 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 54358
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

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.

Conditions

Epilepsy

Keywords

Perampanel; Cognition

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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 Outcomes (2)

• 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.

  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.

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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

PER 1 Week Titration

EXPERIMENTAL

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

Drug: Perampanel 1 week titration

PER 2 Week Titration

EXPERIMENTAL

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

Drug: Perampanel 2 week titration

PER 4 mg

EXPERIMENTAL

Participants will take 4mg perampanel PO QD for six weeks

Drug: Perampanel 4mg

Interventions

Perampanel 1 week titration DRUG

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

Also known as: Fycompa

PER 1 Week Titration

Perampanel 2 week titration DRUG

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

Also known as: Fycompa

PER 2 Week Titration

Perampanel 4mg DRUG

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

Also known as: Fycompa

PER 4 mg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults between the ages of 18 and 55 years
• Male or female (using approved birth control methods)
• Informed consent obtained

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kimford Jay Meador: lead
• Eisai Inc.: collaborator

Study Sites (3)

Stanford University

Palo Alto, California, 94304, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

New York University

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Epilepsy

Interventions

perampanel

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Enrollment was delayed due to the COVID-19 pandemic. The sponsor then decided to no longer fund the study. These caused total enrollment to be low, preventing statistical analyses from being conducted.

Results Point of Contact

• Title: Kimford Meador
• Organization: Stanford University

kmeador@stanford.edu

650-721-5552

Study Officials

• Kimford Meador, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology and Neurological Sciences

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: June 5, 2020
• Study Start: October 20, 2021
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: June 6, 2024
• Results First Posted: June 6, 2024

Record last verified: 2024-05

Locations

US (3)