<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/NCT02220972</url>
  </required_header>
  <id_info>
    <org_study_id>E2007-A001-408</org_study_id>
    <nct_id>NCT02220972</nct_id>
  </id_info>
  <brief_title>To Evaluate the Effect of Perampanel on Objective and Subjective Sleep in Subjects With Insomnia and Partial Onset Seizures</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effect of Perampanel on Objective and Subjective Sleep in Subjects With Insomnia and Partial Onset Seizures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eisai Inc.</source>
  <brief_summary>
    <textblock>
      This will be a multi-center, randomized, double-blind, placebo-controlled, crossover study to&#xD;
      evaluate the effects of 2007/Fycompa (perampanel) on sleep, in subjects with well controlled&#xD;
      partial onset seizures (on an antiepileptic drug [AED] monotherapy) who are experiencing&#xD;
      sleep onset insomnia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Anticipated">August 2016</completion_date>
  <primary_completion_date type="Anticipated">August 2016</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in latency to persistent sleep (LPS) using Polysomnography (PSG)</measure>
    <time_frame>Baseline, week 5 and week 14</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Sleep Efficiency (SE) using Polysomnography (PSG)</measure>
    <time_frame>Baseline, week 5 and week 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Subjective Sleep onset Latency (SSOL) using Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>Baseline, week 5 and week 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean reciprocal reaction time on Psychomotor Vigilance Task (PVT) to assess sustained attention</measure>
    <time_frame>Baseline, week 5 and week 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short delay and long delay verbal recall using Rey Auditory Verbal Learning Test (RAVLT)</measure>
    <time_frame>Baseline, week 5 and week 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure number of seizures using Seizure Diary</measure>
    <time_frame>baseline up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure severity of suicidal ideation and behavior by eC-SSRS Electronic version of the Columbia Suicide Severity Rating Scale</measure>
    <time_frame>baseline up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of Perampanel as a measure of Adverse Events/ Serious Adverse Events</measure>
    <time_frame>baseline up to 18 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Epilepsy, Partial</condition>
  <arm_group>
    <arm_group_label>Arm A: First on Perampanel with a crossover to Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment Arm A will initially receive perampanel 2 mg QD titrated up to 4 mg QD and finally to 6 mg QD with a crossover to placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: First on Placebo with a crossover to Perampanel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment Arm B will initially receive placebo with a crossover to perampanel 2 mg QD titrated up to 4 mg QD and finally to 6 mg QD.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perampanel</intervention_name>
    <arm_group_label>Arm A: First on Perampanel with a crossover to Placebo</arm_group_label>
    <arm_group_label>Arm B: First on Placebo with a crossover to Perampanel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Arm A: First on Perampanel with a crossover to Placebo</arm_group_label>
    <arm_group_label>Arm B: First on Placebo with a crossover to Perampanel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Have a diagnosis of epilepsy with partial onset seizures with or without secondary&#xD;
             generalization, according to the ILAE Classification of Epileptic Seizures (1981).&#xD;
             Diagnosis should have been established by clinical history, with chart confirmation of&#xD;
             previous EEG that is consistent with localization-related epilepsy; normal interictal&#xD;
             EEGs will be allowed provided that the subject meets the other diagnosis criterion&#xD;
             (ie, clinical history).&#xD;
&#xD;
          2. Subjects will be well controlled (defined as less than 1 seizure every 28 days) for a&#xD;
             period of at least 3 months on a current AED monotherapy (defined as a single AED&#xD;
             taken for at least 28 days before Screening), and have no history of AED polytherapy.&#xD;
&#xD;
          3. Male or female subjects, at least 18 years and no more than 50 years of age at the&#xD;
             time of informed consent&#xD;
&#xD;
          4. Body Mass Index of 18 to 30 kg/m2&#xD;
&#xD;
          5. Meets Diagnostic and Statistical Manual-5 criteria for Insomnia Disorder:&#xD;
&#xD;
               1. Complains of dissatisfaction with nighttime sleep in the form of difficulty&#xD;
                  getting to sleep or difficulty staying asleep&#xD;
&#xD;
               2. Frequency of complaint is at least 3 times per week&#xD;
&#xD;
               3. Duration of complaint is at least 3 months&#xD;
&#xD;
               4. Associated with complaint of daytime impairment&#xD;
&#xD;
          6. Confirmed problems with sleep onset insomnia as evidenced by response to &quot;Time to Fall&#xD;
             Asleep&quot; question on the PSQI at Screening of at least 45 minutes&#xD;
&#xD;
          7. Confirmed problems with sleep onset insomnia as evidenced by habitual median sSOL of&#xD;
             at least 45 minutes obtained from sleep diary responses for the last consecutive 7&#xD;
             days of the Screening/Baseline Period&#xD;
&#xD;
          8. Confirmed problems with sleep onset insomnia as evidenced by LPS of at least 20&#xD;
             minutes on the baseline PSG&#xD;
&#xD;
          9. Provide written informed consent, signed by the subject before entering the study or&#xD;
             undergoing any study procedures&#xD;
&#xD;
         10. Willing and able to comply with all aspects of the protocol&#xD;
&#xD;
         11. Females must not be lactating or pregnant at Screening or Baseline (as documented by a&#xD;
             negative beta-human chorionic gonadotropin [B-hCG] or a human chorionic gonadotropin&#xD;
             [hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG [or&#xD;
             hCG]). A separate baseline assessment is required if a negative screening pregnancy&#xD;
             test was obtained more than 72 hours before the first dose of study drug.&#xD;
&#xD;
         12. All females will be considered to be of childbearing potential unless they are&#xD;
             postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age&#xD;
             group, and without other known or suspected cause) or have been sterilized surgically&#xD;
             (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with&#xD;
             surgery at least 1 month before dosing).&#xD;
&#xD;
         13. Females of childbearing potential must not participate in a conception process (ie,&#xD;
             active attempt to become pregnant or to impregnate, in vitro fertilization) and must&#xD;
             not have had unprotected sexual intercourse within 30 days before study entry and must&#xD;
             agree to use a highly effective method of contraception (eg, total abstinence, an&#xD;
             intrauterine device, a double-barrier method [such as condom plus diaphragm with&#xD;
             spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized&#xD;
             partner with confirmed azoospermia), for at least 4 weeks before dosing, throughout&#xD;
             the entire study period and for 4 weeks after study drug discontinuation. If currently&#xD;
             abstinent, the subject must agree to use a double-barrier method as described above if&#xD;
             she becomes sexually active during the study period or for 4 weeks after study drug&#xD;
             discontinuation. Females who are using hormonal contraceptives must have been on a&#xD;
             stable dose of the same hormonal contraceptive product for at least 4 weeks before&#xD;
             dosing and must continue to use the same contraceptive during the study and for 4&#xD;
             weeks after study drug discontinuation.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Hypersensitivity to any component of Fycompa&#xD;
&#xD;
          2. Subjects with other sleep problems (except for sleep onset or mixed sleep onset and&#xD;
             sleep maintenance insomnia) based on history, standard sleep questionnaires, and PSG&#xD;
             at Screening.&#xD;
&#xD;
          3. Subjects with a diagnosis of a sleep-related breathing disorder, apnea-hypopnea index&#xD;
             of more than 15, periodic limb movement disorder of more than 15, restless legs&#xD;
             syndrome, nightmare disorder, sleep terror disorder, sleepwalking disorder, REM&#xD;
             behavior disorder, narcolepsy, or circadian rhythm sleep disorder.&#xD;
&#xD;
          4. Subjects with current evidence of unstable psychotic disorder, major depressive&#xD;
             disorder, bipolar disorder, or generalized anxiety disorder based on a psychiatric&#xD;
             interview at Screening, or subjects diagnosed with psychotic disorder or major&#xD;
             depressive disorder within 2 years before Screening based on clinical history&#xD;
&#xD;
          5. Subjects on strong cytochrome P450 (CYP) 3A inducers other than AEDs (eg, rifampin,&#xD;
             St. John's Wort)&#xD;
&#xD;
          6. Subjects on EIAEDs: carbamazepine, oxcarbazepine, and phenytoin or eslicarbazepine&#xD;
             (presumed EIAED)&#xD;
&#xD;
          7. Using a prescription or over the counter medication for the purpose of treating sleep&#xD;
             disturbance, including sedating antihistamines, within 14 days before dosing&#xD;
&#xD;
          8. Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or&#xD;
             planning to travel across more than 3 time zones during the study&#xD;
&#xD;
          9. Excessive caffeine use (defined as more than 4 cups of coffee a day, or its&#xD;
             equivalent)&#xD;
&#xD;
         10. Shift workers, defined as subjects who typically start work hours after 16:00 (4 pm)&#xD;
             or before 4:00 (4 am)&#xD;
&#xD;
         11. Any history of a medical condition or concomitant medical condition that in the&#xD;
             opinion of the investigator(s) would compromise the subject's ability to safely&#xD;
             complete the study, including significantly abnormal laboratory results or any&#xD;
             physical or mental condition that prevents compliance with the protocol&#xD;
&#xD;
         12. Use of illegal recreational drugs or recent history (within 2 years before the&#xD;
             Screening Visit) of alcohol or drug/solvent dependency or abuse or a positive screen&#xD;
             for drugs of abuse using a standard Urine Drug Screen at Screening&#xD;
&#xD;
         13. A clinically significant electrocardiogram (ECG) abnormality, including a prolonged QT&#xD;
             interval/corrected QT interval defined as more than 450 msec based on an ECG at&#xD;
             Screening&#xD;
&#xD;
         14. Currently enrolled in another clinical study or participated in any clinical study&#xD;
             with an investigational drug, biologic, or device within 1 month before Screening&#xD;
             (Visit 1), or within approximately 5 half-lives of the previous investigational&#xD;
             compound, whichever is longer&#xD;
&#xD;
         15. Previous use of perampanel or participated in previous perampanel studies&#xD;
&#xD;
         16. Any suicidal ideation with intent with or without a plan at Screening or Baseline or&#xD;
             within 6 months before Screening (ie, answering 'Yes' to questions on the Suicidal&#xD;
             Ideation section of the electronic version of the Columbia Suicide Severity Rating&#xD;
             Scale [eC-SSRS])&#xD;
&#xD;
         17. Suicide attempt(s) within approximately the last 2 years or suicidal ideation within&#xD;
             the last 6 months before the Screening visit (using the Suicidal Behavior Section of&#xD;
             the eC-SSRS)&#xD;
&#xD;
         18. Evidence of significant active hepatic disease. Stable elevations of liver enzymes,&#xD;
             alanine aminotransferase and aspartate aminotransferase due to concomitant&#xD;
             medication(s) will be allowed if they are less than 3 times the upper limit of normal&#xD;
&#xD;
         19. Evidence of clinically significant disease (eg, cardiac, respiratory,&#xD;
             gastrointestinal, renal disease) that in the opinion of the Investigator(s) could&#xD;
             affect the subject's safety or interfere with the study assessments&#xD;
&#xD;
         20. Presence of a progressive central nervous system (CNS) disease, including degenerative&#xD;
             CNS diseases and progressive tumors&#xD;
&#xD;
         21. Presence of an implanted vagal nerve stimulator&#xD;
&#xD;
         22. Have had multiple drug allergies or a severe drug reaction to an AED, including&#xD;
             dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>February 9, 2015</last_update_submitted>
  <last_update_submitted_qc>February 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 10, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Epilepsy</keyword>
  <keyword>Partial Onset Seizures</keyword>
  <keyword>Insomnia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
    <mesh_term>Seizures</mesh_term>
    <mesh_term>Epilepsies, Partial</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/NCT02220972
org study id: E2007-A001-408
nct id: NCT02220972
lead sponsor: 
This will be a multi-center, randomized, double-blind, placebo-controlled, crossover study to
      evaluate the effects of 2007/Fycompa (perampanel) on sleep, in subjects with well controlled
      partial onset seizures (on an antiepileptic drug [AED] monotherapy) who are experiencing
      sleep onset insomnia.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline in latency to persistent sleep (LPS) using Polysomnography (PSG)
time frame: Baseline, week 5 and week 14
measure: Change from baseline in Sleep Efficiency (SE) using Polysomnography (PSG)
time frame: Baseline, week 5 and week 14
measure: Change from baseline in Subjective Sleep onset Latency (SSOL) using Pittsburgh Sleep Quality Index (PSQI)
time frame: Baseline, week 5 and week 14
measure: Mean reciprocal reaction time on Psychomotor Vigilance Task (PVT) to assess sustained attention
time frame: Baseline, week 5 and week 14
measure: Short delay and long delay verbal recall using Rey Auditory Verbal Learning Test (RAVLT)
time frame: Baseline, week 5 and week 14
measure: Measure number of seizures using Seizure Diary
time frame: baseline up to 18 weeks
measure: Measure severity of suicidal ideation and behavior by eC-SSRS Electronic version of the Columbia Suicide Severity Rating Scale
time frame: baseline up to 18 weeks
measure: Safety and tolerability of Perampanel as a measure of Adverse Events/ Serious Adverse Events
time frame: baseline up to 18 weeks
arm group label: Arm A: First on Perampanel with a crossover to Placebo
arm group type: Experimental
description: Treatment Arm A will initially receive perampanel 2 mg QD titrated up to 4 mg QD and finally to 6 mg QD with a crossover to placebo.
arm group label: Arm B: First on Placebo with a crossover to Perampanel
arm group type: Experimental
description: Treatment Arm B will initially receive placebo with a crossover to perampanel 2 mg QD titrated up to 4 mg QD and finally to 6 mg QD.
intervention type: Drug
intervention name: Perampanel
arm group label: Arm A: First on Perampanel with a crossover to Placebo
arm group label: Arm B: First on Placebo with a crossover to Perampanel
intervention type: Drug
intervention name: Placebo
arm group label: Arm A: First on Perampanel with a crossover to Placebo
arm group label: Arm B: First on Placebo with a crossover to Perampanel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Epilepsy
mesh term: Sleep Initiation and Maintenance Disorders
mesh term: Seizures
mesh term: Epilepsies, Partial