Clinical trial NCT03653741
Conditions: Healthy
Sponsor: Weill Medical College of Cornell University
Start date: 2018-10-01; Completion date: 2021-11-29
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a study to evaluate the effects of perampanel, a FDA approved drug for epilepsy, on commonly performed neurophysiology tests: electroencephalogram (EEG), somatosensory evoked potential (SEP), brainstem auditory evoked potential (BAEP), and visual evoked potential (VEP). Many other drugs used in the treatment of epilepsy have been shown to affect the results of these test but no one has yet examined if perampanel affects these tests. The investigators plan to recruit 12 healthy normal male subjects. All subjects will have VEP, SSEP, EEG, and BAER performed before and 1 hour (when Cmax is reached) after receiving 6mg of oral perampanel. Subjects will also receive a blood draw 1 hour after ingestion of perampanel for serum perampanel level. In a previous study done at another institution, healthy volunteers have tolerated a single dose of perampanel at 6 mg quite well. There is no placebo nor randomization. Subject's participation concludes after completion of post-perampanel ingestion neurophysiology tests.

Detailed description:
The study drug used in this research study is perampanel, an FDA approved medication for the treatment of seizures. The study is being done to examine whether the study drug affects the following non-invasive tests of brain activity: electroencephalogram (EEG), visual evoked potential (VEP), brainstem auditory evoked potential (BAER), and somatosensory evoked potential (SEP). Many anti-seizure drugs have been shown to affect these 4 tests. Anti-seizure medications such as phenytoin, carbamazepine, and oxcarbazepine have been shown to cause slowing of brain activity on EEGs. To date, there have been no published data on whether perampanel, affects EEG, VEP, SEP, or BAER. The data from this study may help with interpretation of these tests in epileptic patients on perampanel.

The investigators are looking for male participants with no prior chronic medical conditions to partake in this study.

All participants will undergo the following tests as part of the study:

1. EEG: this test monitors the electrical activity of the brain through small, metal disks (electrodes) that are placed on the scalp. The test is painless and after the electrodes are placed, participants will be asked to lay down as brain activity is monitored.
2. VEP: this test is similar to the EEG in that electrodes will be placed on the back of the head to monitor brain electrical activity. This test looks specifically at what is happening in the part of the brain that responds to vision, so during the test participants will be shown visual stimuli like a bright light or image on a screen to stimulate brain activity.
3. BAER: this test is similar to the EEG in that electrodes will be placed on participant's head to monitor brain electrical activity. This test looks specifically at what is happening in the part of the brain that responds to sound, so during the test, different sounds will be played to stimulate brain activity.
4. SEP: this test is similar to the EEG in that electrodes will be placed on participant's head to monitor brain electrical activity. This test looks specifically at what is happening in the part of the brain that responds to touch and body sensations, so electrodes will also be placed on the arms and legs to stimulate that area with an electric pulse. This electrical stimulation can cause mild discomfort but is generally well tolerated. Participants may feel muscles twitch when the electrical stimulation is given.

These tests are non-invasive and done routinely in the evaluation of neurologic diseases. They are well tolerated and have no long term side effects.

Following the completion of the four tests, participants will take a single dose of 6mg pill of perampanel:

Perampanel is a drug approved and marketed in the USA for the treatment of epilepsy to prevent recurrent seizures. In a previous study, healthy volunteers have tolerated a single dose of perampanel at 6 mg quite well.

Following taking the pill of perampanel, participants will have their blood drawn:

Participants will have their blood drawn approximately 1 hour after ingestion of single dose of perampanel to measure the concentration of the drug in their blood stream. The total amount of blood taken during the study is approximately 40-60 teaspoons.

After the blood draw, participants will repeat the four tests (EEG, VEP, BAER, SEP) as described above.

There is no follow up visit. However, the study physician will be available should participants experience unexpected side effects due to the study. The investigators, physicians, or sponsors may stop the study or take participants out of the study at any time should they judge that it is in participants' best interest to do so. For instance, they may take participants out of the study if they experience a study-related injury or if they are unable to undergo testing. They may remove participants from the study for various other administrative and medical reasons. They can do this without consent.

For trials of drugs, there may be risks. The research doctor will discuss the full extent of diagnostic, procedural, and drug risks with participants. There may be risks which are currently unforeseeable. As with all medications, side effects may occur and there may be additional side effects, including long term effects, which are at present unknown. Therefore, it is important that participants report any adverse reactions to the study doctor immediately.

In the period immediately following the study, participants should use caution when driving or using heavy machinery, since the study drug may cause imbalance, dizziness or fatigue.

Participants should not take perampanel if theyare allergic to any of the ingredients in the tablet.

Serious Side Effects:

Perampanel may cause new or worse aggressive behavior, homicidal thoughts or threats, hostility, anger, anxiety, irritability, being suspicious or distrustful (believing things that are not true), and other unusual or extreme changes in behavior or mood. Extreme behavioral changes have not been seen in a study of only a single dose of perampanel, and it is not expected that participants will develop such behavioral changes. Participants should contact the study doctor immediately should they experience any of the above.

Antiepileptic drugs, including perampanel, may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Subjects should call their healthcare providers right away if they have any of the following symptoms, especially if they are new, worse, or worrisome: thoughts about suicide or dying, thoughts of self-harm, attempt to commit suicide, new or worse depression, new or worse anxiety, feeling agitated or restless, panic attacks, trouble sleeping (insomnia), new or worse irritability, acting aggressive, being angry or violent, acting on dangerous impulses, an extreme increase in activity and talking (mania), and other unusual changes in behavior or mood. Participants should call the study doctor immediately if they notice any changes in mood, ideas or behavior.

Most common side effects:

Dizziness, fatigue, sleepiness, irritability, falls, nausea, imbalance, gait problems, vertigo, and weight gain.

Less commonly seen side effects:

Headache, anxiety, upset stomach, vomiting, constipation, urinary tract infection, problems with coordination, rash, bruises, muscle pain, blurry vision, swelling of arms/legs, numbness, memory problems, confusion, euphoria, low blood sodium level, increase triglyceride level, skin laceration, pain in extremities, back pain, and head trauma. Though rare, skin laceration, head trauma, pain in extremities, and back pain are possible with this medication due to imbalance and dizziness leading to falls.

Additional Risks:

The U.S Drug Enforcement Agency (DEA) may classify some, but not all, medicines as controlled substances. Perampanel has been classified as schedule III. Medicines in this category have an approved medical use but have potential for abuse, physical dependence, or psychological dependence. The risk is lower compared to drugs in Schedule I and II. Some other anti-epileptic medicines have also been listed as controlled substances.

It is possible that perampanel may interact with other medicines and herbal supplements that participants are taking. Before starting the study, the study doctor will determine that they are not taking anything that can interact with perampanel.

During the collection of blood samples, participants may experience slight discomfort and a small amount of bleeding, discoloration or bruising at the site where the needle was inserted. Clot formation and infections may occur at the puncture site, but this is extremely rare. Fainting may occur during or shortly after having blood drawn. If faintness is experienced, participants should lie down immediately to avoid possible injury caused by falling, and notify the site study staff.

Perampanel does not affect the ability of men to father children.

Risks of the Tests:

For all fours tests (EEG, VEP, BAER, SEP), participants may experience discomfort from the placement of the electrodes on the scalp. Participants may also experience visual discomfort when they are shown bright lights during the VEP, as well as hearing discomfort when they hear sounds during the BAER. Finally, participants may experience brief discomfort during the SEP when electrical stimulus is created by the electrodes on the arms or legs. These electrical shocks are done as part of routine exams in patients with possible nerve damages and are generally well tolerated. There are no long lasting effects from these mild shocks.

Efforts will be made to protect participants' medical records and other personal information to the extent allowed by law. However, the investigator cannot guarantee absolute confidentiality. Records of study participants are stored and kept according to legal requirements and may be part of participants' medical record. Participants will not be identified personally in any reports or publications resulting from this study. Organizations that may request to inspect and/or copy participants' research and medical records for quality assurance and data analysis include groups such as:

* Weill Cornell Medical College and NewYork-Presbyterian Hospital
* The Institutional Review Board (IRB)
* The Office of Human Research Protection (OHRP)
* The Food and Drug Administration (FDA) and/or their representatives
* Eisai, Inc. The results of this study may be presented at meetings or in publications; however, participants' identities will not be disclosed in these presentations.

Biological samples may be collected, processed, and reported as necessary for purposes of the study. In the event anyone involved with this study is exposed to participants' blood or bodily fluids, it blood may be tested for evidence of hepatitis, AIDS, or other infections without participants' further consent. Participants will be notified of the results.

By signing the consent form, participants authorize the study doctor to release participants' study-related records to Eisai, Inc., the FDA, the IRB, or any other regulatory authority. By signing the consent form, participants authorize access to this confidential information. Participants also authorize the release of their medical records to Weill Cornell Medical College and NewYork-Presbyterian Hospital by any other hospitals or institutions where participants might receive medical care of any kind while they are participating in this study.

The investigator will not be charging participants any fees to participate in this study.

Participants or their insurance companies will be charged for continuing medical care and/or hospitalization that is not a part of the research study.

Participants will be compensated 200 dollars in cash within 2 weeks after completing the study.

Participants should not expect anyone to pay them for pain, worry, lost income, or non-medical care costs that occur from taking part in this research study. Participants should expect no compensation or reimbursement for these costs or any risks and anxieties associated with any such follow up care. Participants or their insurance companies will also be charged for any continuing medical care and/or hospitalization that are not a part of the study.

Arms: arm 1: healthy males will undergo EEG, VEP, BAER, and SEP testing, then take a single dose of Perampanel 6 MG pill (intervention), then have blood drawn and undergo the 4 tests mentioned previously for a second time
Interventions: intervention 1: Perampanel 6 MG
Intervention descriptions: intervention 1: Perampanel is a drug approved and marketed in the USA for the treatment of epilepsy to prevent recurrent seizures. In a previous study, healthy volunteers have tolerated a single dose of perampanel at 6 mg quite well.

Protocol documents:
Prot_002.pdf: 
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PROTOCOL TITLE: Effects of Perampanel on Neurophysiology Test Perimeters 
 
PRINCIPAL INVESTIGATOR: David Chuang, MD Weill Cornell Medicine 
IRB Protocol #: 1704018150 
ClinicalTrials.gov Identifier: #NCT03653741 
 
Current Version 6/1/2018 
 
Prior Version Dates:  
Version December 8, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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BACKGROUND 
Neurophysiology tests such as EEG, VEP, BAER, and SEP are used to evaluate the functional status of the 
neuroaxis from the periphery all the way to the cortex. Many anti-epileptic drugs have been shown to 
affect these tests. Anti-epileptic medications such as phenytoin, carbamazepine, and oxcarbazepine 
have been shown to cause background slowing on EEG. Anti-epileptic medications have also been 
shown to prolong latency values in VEP, SSEP and BAER. One small study demonstrated that the AMPA 
receptor antagonist talampanel was associated with dose-dependent increase in beta activity.  To date, 
there have been no published data on whether FDA approved anti-epileptic medication perampanel 
(same mechanism of action as talampanel) affects EEG, VEP, SSEP, or 
BAER.  As for anticipated side effects of perampanel, in a small study of 6 patients that received a single 
dose of perampanel at 6mg (the dose we will be using), the most common side effects was headache, 
fatigue, somnolence, and dizziness. 
STUDY DESIGN 
We hypothesize that perampanel, a FDA approved drug for epilepsy, will affect commonly performed 
neurophysiology tests: electroencephalogram (EEG), somatosensory evoked potential (SEP), brainstem 
auditory evoked potential (BAEP), and visual evoked potential (VEP). More specifically, we hypothesize it 
will decrease background frequency content in EEG and increase latency in VEP, SEP, and BAEP. We plan 
to recruit 12 healthy normal male subjects. All subjects will have VEP, SSEP, EEG, and BAER performed 
before and 1 hour (when Cmax is reached) after receiving 6mg of perampanel. Subjects will also receive 
a blood draw 1 hour after ingestion of perampanel for serum perampanel level for correlation with any 
changes seen in the neurophysiology test data. There is no placebo nor randomization. Subject's 
participation concludes after completion of post-perampanel ingestion neurophysiology tests.  
Primary: Quantify the effects of perampanel on electroencephalography, visual evoked potential, 
somatosensory evoked potential, and brainstem auditory evoked potential to guide interpretation of 
test results for patients taking perampanel.  
Secondary: 1) Correlate effects on neurophysiology test perimeters with known drug side effects. 2) 
Pinpoint where in neuroaxis perampanel exerts maximal effects, which may shed light on where it exerts 
its anti-seizure effects. 
Based on similar studies, we will recruit 12 subjects. Each subject will undergo 4 neurophysiology tests. 
Then each subject will ingest perampanel and then repeat the 4 neurophysiology tests. We will compare 
the pre-ingestion to the post-ingestion values in the 4 tests using a Wilcoxon signed-rank test, which is 
more appropriate for small samples than a standard paired t-test. We do not expect any dropouts, but if 
they occur we will perform sensitivity analysis by providing results for different imputed values for the 
dropouts. 
INCLUSION AND EXCLUSION CRITERIA 
Healthy subjects between the ages of 18 to 50 years old with a body mass index of 19-29 kg/m2 will be 
recruited. Subjects would be excluded if they use recreational drugs and have any neurologic disease, 
psychiatric condition or any other condition that may affect outcome and risk subject safety. 


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Furthermore, anyone that would not be able to participate in neurophysiology tests will also be 
excluded. Subject will also be excluded should they take any over the counter medication or consume 
caffeine or alcohol 12 hours prior to the study. 
 
DATA AND SAFETY MONITORING PLAN 
The risk to subjects is minimal risk for all tests involved. Blood levels of perampanel will be drawn 1 hour 
after drug administration. Additionally, the 4 tests (VEP, EEG, SEP, BAEP) will be completed both prior to 
and following study drug administration. This study does not have interim and complete stopping rules. 
This is a small study and we do not expect to encounter any major adverse events since the tests we will 
be administering is well tolerated and the study drug, perampanel, is FDA approved and well tolerated 
in the way we will be administering it (single dose at 6mg). We do not expect any adverse events that 
would stop a subject's participation. The subject can withdraw voluntarily. The risk of taking perampanel 
to the subject is classified as greater than minimal risk. In a small  study  looking  at  single  dose of 
perampanel administered to healthy volunteer at 6mg, the reported side effects were headache, 
dizziness (excluding vertigo), somnolence, and fatigue. These were all classified as mild to moderate in 
severity. Rate of side effect was reported as 16.8% while placebo was 12.6%. Serious Side Effects: 
Perampanel may cause new or worse aggressive behavior, homicidal thoughts or threats, hostility, 
anger, anxiety, irritability, being suspicious or distrustful (believing things that are not true), and other 
unusual or extreme changes in behavior or mood. You should contact the study doctor immediately 
should you experience any of the above. Antiepileptic drugs, including perampanel, may cause suicidal 
thoughts or actions in a very small number of people, about 1 in 500. Study subjectss should call their 
healthcare providers right away if they have any of the following symptoms, especially if they are new, 
worse, or worrisome: thoughts about suicide or dying, thoughts of self-harm, attempt to commit 
suicide, new or worse depression, new or worse anxiety, feeling agitated or restless, panic attacks, 
trouble sleeping (insomnia), new or worse irritability, acting aggressive, being angry or violent, acting on 
dangerous impulses, an extreme increase in activity and talking  (mania), and other unusual changes in 
behavior or mood. You should call your study doctor immediately if you notice any changes in mood, 
ideas or behavior. Most common side effects: Dizziness, fatigue, sleepiness, irritability, falls, nausea, 
imbalance, gait problems, vertigo, and weight gain. Less commonly seen side effects: Headache, anxiety, 
upset stomach, vomiting, constipation, urinary tract infection, problems with coordination, rash, bruises, 
muscle pain, blurry vision, swelling of arms/legs, numbness, memory problems, confusion, euphoria, low 
blood sodium level, increase  triglyceride  level, skin laceration,  pain  in  extremities, back pain, and  
head  trauma.  Additional Risks: The U.S Drug Enforcement Agency (DEA) may classify some, but not all, 
medicines as controlled substances. Perampanel has been classified as schedule III. Medicines in this 
category have an approved medical use but have potential for abuse, physical dependence, or 
psychological dependence. The risk  is   lower   compared   to   drugs in Schedule I and II. Some other 
anti-epileptic medicines have also been listed as controlled substances. It is possible that perampanel 
may interact with other medicines and herbal supplements that you are taking. Before starting the 
study, your study doctor will determine that you are not taking anything that can interact with 
perampanel. During the collection of blood samples, you may experience slight discomfort and a small 
amount of bleeding, discoloration or bruising at the site where the needle was inserted. Clot formation 
and infections may occur at the puncture site, but this is extremely rare. Fainting may occur during or 


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shortly after having blood drawn. If faintness is experienced, you should lie down immediately to avoid 
possible injury caused by falling and notify the site study staff. The total amount of blood taken during 
the study is approximately 40-60 teaspoons. Reproductive Risks: Perampanel does not affect the ability 
of men to father children. 
Subjects will be monitored during the tests and interviewed in order to detect any adverse events. An 
investigator will be with the subject at all times to recognize and record any adverse events. Since the 
study involves only one dosing of study drug, there will not be any negative impact on subjects resulting 
from study closure or a subject being terminated from the study. Adverse events will be rated mild, 
moderate, or severe. Adverse events will be reported to the IRB and to Eisai (study sponsor). Aside from 
the IRB, unexpected adverse events will also be promptly reported to Eisai. The principle investigator 
will be monitoring the safety of the subjects. 
Interim analysis will not be needed as drug is FDA approved and small study so analysis will be done 
after completion of all subject. Data safety monitoring board is not needed since drug is FDA approved 
and will be administered only once to normal subjects. It is found to be generally well tolerated in this 
condition.