EpilepsyPhase 4NCT04417907

Perampanel Titration and Cognitive Effects

A Phase 4 study testing Perampanel 1 week titration, Perampanel 2 week titration and Perampanel 4mg in people with Epilepsy, run by Kimford Jay Meador at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Epilepsy
What is being tested?: Perampanel 1 week titration, Perampanel 2 week titration and Perampanel 4mg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 29 participants
Where: 3 sitesUnited States
Study dates: 20 Oct 2021to 1 May 2023
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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.

Show all 10Show fewer

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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Northwestern University
Chicago, Illinois, 60611
New York University
New York, New York, 10016
Stanford University
Palo Alto, California, 94304

Other trials in United States

About this study

Official title: Effects of Titration Rate on Cognitive and Behavioral Side Effects of Perampanel

Read the 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.

Conditions: Epilepsy
Being tested: Perampanel 1 week titration, Perampanel 2 week titration, Perampanel 4mg, Placebo
Keywords: Perampanel, Cognition
Medical subject headings: Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Perampanel 1 week titrationDrug
Also called Fycompa
Healthy adults will take 2mg perampanel PO QD for one week followed 4mg perampanel PO QD for five weeks.
Perampanel 2 week titrationDrug
Also called Fycompa
Healthy adults will take 2mg perampanel PO QD for two weeks followed 4mg perampanel PO QD for four weeks.
Perampanel 4mgDrug
Also called Fycompa
Healthy adults will take 4mg perampanel PO QD for six weeks
PlaceboDrug
Healthy adults will take 2mg placebo PO QD for six weeks

Study groups in NCT04417907
Study group	Role	What they receive
Placebo	Placebo comparator	Participants will take 2mg placebo PO QD for six weeks. Receives: 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. Receives: 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. Receives: Drug: Perampanel 2 week titration
PER 4 mg	Experimental	Participants will take 4mg perampanel PO QD for six weeks Receives: Drug: Perampanel 4mg

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Oct 20211 May 2023

First posted5 Jun 2020
Study start20 Oct 2021
Primary completion1 May 2023
Study completion1 May 2023

Why it stopped: Study sponsor no longer provided funding.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for EpilepsyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04417907
Sponsor's protocol ID: 54358
Status last verified: May 2024
First submitted: 2 Jun 2020
Last updated: 6 Jun 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Tumor Related Epilepsy
Epilepsy, Cancer
Enrolling by invitation
An Examination of Cognitive and Sensorimotor Processes in Patients With Epilepsy
Epilepsy
RecruitingObservational study
Investigating Epilepsy: Screening and Evaluation
Seizures, Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy
Enrolling by invitationObservational study
Neurophysiological Intraoperative or Epilepsy Monitoring
Patients Operated on at the Neurosurgery Department

All Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Titration Rate on Cognitive and Behavioral Side Effects of Perampanel
ClinicalTrials.gov ID: NCT04417907
Acronym / sponsor ID: 54358
Conditions: Epilepsy
Keywords: Perampanel, Cognition
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study sponsor no longer provided funding.
Enrolment: 29 participants (actual)
Lead sponsor: Kimford Jay MeadorUniversity, hospital or other
Collaborators: Eisai Inc.
Study start: 20 Oct 2021 (actual)
Primary completion: 1 May 2023 (actual)
Study completion: 1 May 2023 (actual)
First posted: 5 Jun 2020 (actual)
Results: Posted 6 Jun 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboParticipants will take 2mg placebo PO QD for six weeks.
PER 1 Week Titration	Experimental	Drug: Perampanel 1 week titrationParticipants will take 2mg perampanel PO QD for one week, followed by 4mg perampanel PO QD for five weeks.
PER 2 Week Titration	Experimental	Drug: Perampanel 2 week titrationParticipants will take 2mg perampanel PO QD for two weeks, followed by 4mg perampanel PO QD for four weeks.
PER 4 mg	Experimental	Drug: Perampanel 4mgParticipants will take 4mg perampanel PO QD for six weeks

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Perampanel 1 week titrationAlso: FycompaHealthy adults will take 2mg perampanel PO QD for one week followed 4mg perampanel PO QD for five weeks.	Drug	PER 1 Week Titration
Perampanel 2 week titrationAlso: FycompaHealthy adults will take 2mg perampanel PO QD for two weeks followed 4mg perampanel PO QD for four weeks.	Drug	PER 2 Week Titration
Perampanel 4mgAlso: FycompaHealthy adults will take 4mg perampanel PO QD for six weeks	Drug	PER 4 mg
PlaceboHealthy adults will take 2mg placebo PO QD for six weeks	Drug	Placebo

Primary outcome

Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.
Time frame: At the end of each week of treatment for 6 weeks.
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.
Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.
Time frame: At the end of each week of treatment for 6 weeks.
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.
Time frame: At the end of each week of treatment for 6 weeks.
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.

2 secondary outcomes

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.
Time frame: 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.
Time frame: At the end of each week of treatment for 6 weeks.

Results and safety

Results posted to the registry on 6 Jun 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	4	2
PER 1 Week Titration	7	3
PER 2 Week Titration	7	6
PER 4 mg	11	8

Primary outcome: Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.

Time frame: At the end of each week of treatment for 6 weeks.. Mean (Standard Deviation). Unit: score on a scale

Measure	Placebo n = 2	PER 1 Week Titration n = 3	PER 2 Week Titration n = 6	PER 4 mg n = 8
Week 1	-.41 (1.00)	-.07 (.55)	.05 (.28)	.32 (.33)
Week 2	-.25 (.90)	-.01 (.44)	-.15 (.26)	.15 (.27)
Week 3	-.14 (.71)	-.03 (.36)	.02 (.34)	.10 (.34)
Week 4	-.32 (.81)	-.06 (.40)	.09 (.49)	.23 (.33)
Week 5	-.34 (.85)	-.11 (.53)	-.03 (.35)	.37 (.41)
Week 6	-.28 (.87)	-.03 (.45)	-.11 (.35)	.21 (.48)

Population analysed: Participants who completed the protocol are included in the analysis.

Primary outcome: Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.

Time frame: At the end of each week of treatment for 6 weeks.. Mean (Standard Deviation). Unit: score on a scale

Measure	Placebo n = 2	PER 1 Week Titration n = 3	PER 2 Week Titration n = 6	PER 4 mg n = 8
Week 1	-.69 (.52)	.61 (.21)	.04 (.38)	.11 (.23)
Week 2	.26 (.03)	.44 (.20)	-.05 (.02)	.11 (.40)
Week 3	.04 (.30)	.24 (.30)	.05 (.12)	.11 (.11)
Week 4	.51 (.15)	.28 (.23)	-.17 (.38)	.27 (.31)
Week 5	.06 (.19)	.33 (.02)	-.15 (.01)	.07 (.08)
Week 6	.28 (.25)	.11 (.38)	-.21 (.34)	-.06 (.37)

Population analysed: Participants who completed the protocol are included in the analysis.

Primary outcome: Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.

Time frame: At the end of each week of treatment for 6 weeks.. Mean (Standard Deviation). Unit: score on a scale

Measure	Placebo n = 2	PER 1 Week Titration n = 3	PER 2 Week Titration n = 6	PER 4 mg n = 8
Week 1	-.36 (1.08)	-.20 (.50)	.05 (.28)	.36 (.34)
Week 2	-.35 (.96)	-.09 (.43)	-.17 (.28)	.16 (.27)
Week 3	-.28 (.89)	-.23 (.28)	.04 (.44)	.28 (.26)
Week 4	-.47 (.79)	-.12 (.40)	.14 (.51)	.27 (.32)
Week 5	-.41 (.91)	-.19 (.54)	-.01 (.38)	.42 (.43)
Week 6	-.69 (.93)	-.14 (.49)	-.03 (.36)	.41 (.45)

Population analysed: Participants who completed the protocol are included in the analysis.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 8 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 2 (0%)	1 of 2 (50%)	0 of 2
PER 1 Week Titration	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
PER 2 Week Titration	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
PER 4 mg	0 of 8 (0%)	7 of 8 (87.5%)	0 of 8

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Epilepsy

RecruitingObservational study
Tumor Related Epilepsy
Epilepsy, Cancer
Enrolling by invitation
An Examination of Cognitive and Sensorimotor Processes in Patients With Epilepsy
Epilepsy
RecruitingObservational study
Investigating Epilepsy: Screening and Evaluation
Seizures, Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy
Enrolling by invitationObservational study
Neurophysiological Intraoperative or Epilepsy Monitoring
Patients Operated on at the Neurosurgery Department

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kimford Meador, MD principal investigator

Stanford University

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Perampanel 1 week titration, Perampanel 2 week titration and Perampanel 4mg in people with Epilepsy, run by Kimford Jay Meador at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. (time frame: At the end of each week of treatment for 6 weeks.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04417907.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2024.