<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04417907</url>
  </required_header>
  <id_info>
    <org_study_id>54358</org_study_id>
    <nct_id>NCT04417907</nct_id>
  </id_info>
  <brief_title>Perampanel Titration and Cognitive Effects</brief_title>
  <official_title>Effects of Titration Rate on Cognitive and Behavioral Side Effects of Perampanel</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kimford Jay Meador</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to determine whether there are any differences in the&#xD;
      cognitive abilities and/or behavioral response of normal healthy volunteers across different&#xD;
      titration rates of perampanel.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, parallel group design across different titration rates of&#xD;
      perampanel in healthy volunteers. The study consists of 8 visits, 4 of which will occur at&#xD;
      the participant's home, over a 7-week period. One hundred and three (103) normal healthy&#xD;
      subjects will be treated with perampanel (PER) at one of four different titration rates: (1)&#xD;
      2mg/day PER for one week followed by 4mg/day PER for five weeks, (2) 2mg/day PER for two&#xD;
      weeks followed by 4mg/day PER for four weeks, (3) 4mg/day PER for six weeks, or (4) placebo&#xD;
      (0mg/day PER) for six weeks. Cognitive and behavioral function testing along with safety&#xD;
      testing will be conducted at screening, pretreatment baseline, the end of each week during&#xD;
      the titration and maintenance period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 20, 2021</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall neuropsychological composite Z-score as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment.</measure>
    <time_frame>At the end of each week of treatment for 6 weeks plus a baseline measure for control.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite Z-score of objective measures as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment.</measure>
    <time_frame>At the end of each week of treatment for 6 weeks plus a baseline measure for control.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite Z-score of subjective measures as a measure of direct comparison of the 4 titration conditions across 6 weeks of treatment.</measure>
    <time_frame>At the end of each week of treatment for 6 weeks plus a baseline measure for control.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>At the end of the 6 week maintenance period plus a baseline measure for comparison.</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>At the end of the 6 week maintenance period plus a baseline measure for comparison.</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>At the end of the 6 week maintenance period plus a baseline measure for comparison.</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>At the end of each week of treatment for 6 weeks.</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dropouts across the six-week treatment period measure of direct comparison of the 4 titration conditions across 6 weeks of treatment.</measure>
    <time_frame>At the end of each week of treatment for 6 weeks.</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">103</enrollment>
  <condition>Epilepsy</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will take 2mg placebo PO QD for six weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PER 1 Week Titration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will take 2mg perampanel PO QD for one week, followed by 4mg perampanel PO QD for five weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PER 2 Week Titration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will take 2mg perampanel PO QD for two weeks, followed by 4mg perampanel PO QD for four weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PER 4 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will take 4mg perampanel PO QD for six weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perampanel 1 week titration</intervention_name>
    <description>Healthy adults will take 2mg perampanel PO QD for one week followed 4mg perampanel PO QD for five weeks.</description>
    <arm_group_label>PER 1 Week Titration</arm_group_label>
    <other_name>Fycompa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perampanel 2 week titration</intervention_name>
    <description>Healthy adults will take 2mg perampanel PO QD for two weeks followed 4mg perampanel PO QD for four weeks.</description>
    <arm_group_label>PER 2 Week Titration</arm_group_label>
    <other_name>Fycompa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perampanel 4mg</intervention_name>
    <description>Healthy adults will take 4mg perampanel PO QD for six weeks</description>
    <arm_group_label>PER 4 mg</arm_group_label>
    <other_name>Fycompa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Healthy adults will take 2mg placebo PO QD for six weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy adults between the ages of 18 and 55 years&#xD;
&#xD;
          2. Male or female (using approved birth control methods)&#xD;
&#xD;
          3. Informed consent obtained&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic,&#xD;
             neurologic, psychiatric, or renal disease.&#xD;
&#xD;
          2. Presence or history of drug or alcohol abuse or positive urine drug test at screening.&#xD;
&#xD;
          3. The use of concomitant medications, which are known to affect perampanel or the use of&#xD;
             any concomitant medications that may alter cognitive function (see Section VIII.F for&#xD;
             a partial list).&#xD;
&#xD;
          4. Prior adverse reaction to or prior hypersensitivity to perampanel.&#xD;
&#xD;
          5. Prior participation in studies involving perampanel.&#xD;
&#xD;
          6. Subjects who have received any investigational drug within the previous thirty days.&#xD;
&#xD;
          7. Subjects with IQ &lt; 80 as determined by the Peabody Picture Vocabulary Test after&#xD;
             enrollment.&#xD;
&#xD;
          8. Positive pregnancy test. Women of childbearing potential will be required to use&#xD;
             approved birth control methods during the study.&#xD;
&#xD;
          9. Presence of lifetime history of suicide attempt (including an active attempt,&#xD;
             interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6&#xD;
             months as indicated by a positive response ('Yes') to either Question 4 or Question 5&#xD;
             of the C-SSRS at Screening.&#xD;
&#xD;
         10. Invalid results on computerized cognitive tests at screening as indicated by a 'No' on&#xD;
             any of the validity indicators generated in the CNS Vital Signs report.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kimford Meador, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jordan Seliger</last_name>
    <phone>650-460-9260</phone>
    <email>jseliger@stanford.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jordan Seliger, MA</last_name>
      <phone>650-460-9260</phone>
      <email>jseliger@stanford.edu</email>
    </contact>
    <investigator>
      <last_name>Kimford Meador, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Elizabeth Bachman, MPH</last_name>
      <email>elizabeth.bachman@nm.org</email>
    </contact>
    <investigator>
      <last_name>Elizabeth Gerard, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>New York University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Samantha Martin, MA</last_name>
      <email>samantha.martin@nyulangone.org</email>
    </contact>
    <investigator>
      <last_name>Beth Leeman-Markowski, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>February 4, 2023</last_update_submitted>
  <last_update_submitted_qc>February 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Kimford Jay Meador</investigator_full_name>
    <investigator_title>Professor of Neurology and Neurological Sciences</investigator_title>
  </responsible_party>
  <keyword>Perampanel</keyword>
  <keyword>Cognition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04417907
org study id: 54358
nct id: NCT04417907
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
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 plus a baseline measure for control.
description: 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.
measure: 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 plus a baseline measure for control.
description: 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.
measure: 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 plus a baseline measure for control.
description: 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.
measure: 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.
time frame: At the end of the 6 week maintenance period plus a baseline measure for comparison.
description: 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.
measure: 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.
time frame: At the end of the 6 week maintenance period plus a baseline measure for comparison.
description: 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.
measure: 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.
time frame: At the end of the 6 week maintenance period plus a baseline measure for comparison.
description: 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.
measure: 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.
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.
measure: 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.
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.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will take 2mg placebo PO QD for six weeks.
arm group label: PER 1 Week Titration
arm group type: Experimental
description: Participants will take 2mg perampanel PO QD for one week, followed by 4mg perampanel PO QD for five weeks.
arm group label: PER 2 Week Titration
arm group type: Experimental
description: Participants will take 2mg perampanel PO QD for two weeks, followed by 4mg perampanel PO QD for four weeks.
arm group label: PER 4 mg
arm group type: Experimental
description: Participants will take 4mg perampanel PO QD for six weeks
intervention type: Drug
intervention name: Perampanel 1 week titration
description: Healthy adults will take 2mg perampanel PO QD for one week followed 4mg perampanel PO QD for five weeks.
arm group label: PER 1 Week Titration
other name: Fycompa
intervention type: Drug
intervention name: Perampanel 2 week titration
description: Healthy adults will take 2mg perampanel PO QD for two weeks followed 4mg perampanel PO QD for four weeks.
arm group label: PER 2 Week Titration
other name: Fycompa
intervention type: Drug
intervention name: Perampanel 4mg
description: Healthy adults will take 4mg perampanel PO QD for six weeks
arm group label: PER 4 mg
other name: Fycompa
intervention type: Drug
intervention name: Placebo
description: Healthy adults will take 2mg placebo PO QD for six weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kimford Meador, MD
role: Principal Investigator
affiliation: Stanford University
last name: Jordan Seliger
phone: 650-460-9260
email: jseliger@stanford.edu
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Stanford University
investigator full name: Kimford Jay Meador
investigator title: Professor of Neurology and Neurological Sciences
mesh term: Epilepsy