<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/NCT03780907</url>
  </required_header>
  <id_info>
    <org_study_id>E2007-E049-203</org_study_id>
    <nct_id>NCT03780907</nct_id>
  </id_info>
  <brief_title>Safety and Pharmacokinetics Study of E2007 to Treat Partial and Generalised Seizures in People With Epilepsy</brief_title>
  <official_title>A Randomised, Double-Blind, Placebo-Controlled Study of the Tolerability, Safety and Pharmacokinetics of E2007 in Epileptic Patients With Partial and Generalised Seizures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eisai Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this study were to assess the tolerability and safety of E2007 in patients&#xD;
      with refractory partial or generalised seizures and to assess the pharmacokinetics of E2007&#xD;
      in epileptic patients receiving at least one concomitant anti-epileptic drug.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 14, 2003</start_date>
  <completion_date type="Actual">August 6, 2003</completion_date>
  <primary_completion_date type="Actual">August 6, 2003</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with Treatment Emergent Adverse Events (TEAEs)</measure>
    <time_frame>From administration of first dose of study drug up until 42 days.</time_frame>
    <description>The TEAEs were defined as those Adverse Events (AEs) that start on or after the first dose of the treatment until the end of the study. AEs were classified by the investigator as 'not related', 'possibly related' or 'probably related'.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Global Impression of Tolerability (CGIT)</measure>
    <time_frame>Day 28</time_frame>
    <description>The investigator's global impressions of the tolerability of the study treatment was based on a five point scale: 1 - very good, 2 - good, 3 - moderate, 4 - poor, and 5 - very poor.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Parameter: Area Under the Curve (AUC)(0-24hr) of E2007</measure>
    <time_frame>Day 1 and Day 14</time_frame>
    <description>Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. A measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Parameter: Cmax (Maximum Observed Plasma Concentration) of E2007</measure>
    <time_frame>Day 1 and Day 14</time_frame>
    <description>Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. The maximum concentration of a drug observed after its administration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Parameter: Tmax (Time to Maximum Concentration) of E2007</measure>
    <time_frame>Day 1 and Day 14</time_frame>
    <description>Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. The time after dosing when a drug attains its highest measurable concentration (Cmax).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Parameter: Css,min (Minimum Steady State Plasma Concentration) of E2007</measure>
    <time_frame>Day 14</time_frame>
    <description>Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. Lowest plasma concentration within a steady-state dosing interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Parameter: Cav (Average Plasma Concentration) of E2007</measure>
    <time_frame>Day 14</time_frame>
    <description>Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Parameter: Peak-to-trough Fluctuation (PTF) of E2007</measure>
    <time_frame>Day 14</time_frame>
    <description>Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Parameter: Observed Accumulation Ratio (Rac) of E2007</measure>
    <time_frame>Day 14</time_frame>
    <description>Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline of Bond and Lader Scale</measure>
    <time_frame>Baseline, Day 28 and Day 42</time_frame>
    <description>The Bond and Lader visual analogue mood scale (VAMS) had a score from 0 - 100; a higher score represented worsening of the participants condition attributed to 3 factors, (1) Anxiety (e.g., calmness), (2) Sedation (e.g., alertness, (3) Dysphoria (e.g., contentedness). The change was visit minus baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline of Peak Saccadic Velocity (PSV)</measure>
    <time_frame>Baseline, Day 28, Day 42</time_frame>
    <description>Saccadic velocity is the rate of eye movement in response to stimulus. The saccadic eye movement was used to allow comparison of any sedative effects seen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Particpants receiving other Anti-epileptic agents During Treatment</measure>
    <time_frame>Day 1 and Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change from Baseline of Failed Saccades</measure>
    <time_frame>Baseline, Day 28, Day 42</time_frame>
    <description>Failed saccades is stimulus resulting in no eye movement above a defined threshold within a specified time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean trough concentrations of E2007</measure>
    <time_frame>Day 7, Day 21, and Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of seizures</measure>
    <time_frame>Baseline (Day-1) to Day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Clinical Global Impression of Change</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Epilepsy</condition>
  <arm_group>
    <arm_group_label>E2007 1 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet, once daily to be taken in the morning by mouth, one hour before breakfast, with a glass of water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>E2007 2 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet, once daily to be taken in the morning by mouth, one hour before breakfast, with a glass of water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Tablet, once daily to be taken in the morning, one hour before breakfast, with a glass of water.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>E2007</intervention_name>
    <description>1 mg of E2007 was administered by mouth once daily.</description>
    <arm_group_label>E2007 1 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>E2007</intervention_name>
    <description>2 mg of E2007 was administered by mouth once daily.</description>
    <arm_group_label>E2007 2 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo once daily of oral tablet formulation to be taken in the morning, one hour before breakfast, with a glass of water.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        A patient who met the following inclusion criteria was eligible to participate in the&#xD;
        study:&#xD;
&#xD;
          1. Males or females with simple or complex partial seizures with or without secondary&#xD;
             generalization, or primary generalized tonic-clonic seizures according to the&#xD;
             International League against Epilepsy classification. Patient records were to document&#xD;
             the frequency of seizure.&#xD;
&#xD;
          2. Age: 18 to 65 years.&#xD;
&#xD;
          3. Race: any.&#xD;
&#xD;
          4. Patients receiving up to two additional anti-epileptic medications at doses that were&#xD;
             stable for at least the four weeks immediately preceding baseline.&#xD;
&#xD;
          5. Patients willing and able to co-operate with the study procedures including completion&#xD;
             of patient diaries.&#xD;
&#xD;
          6. Patients living at home with a partner or carer able to monitor compliance.&#xD;
&#xD;
          7. Patients giving informed consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        A patient who met the following exclusion criteria was not eligible to participate in the&#xD;
        study:&#xD;
&#xD;
          1. Pregnant or lactating women.&#xD;
&#xD;
          2. Women of childbearing potential unless (1) surgically sterile or (2) practicing&#xD;
             effective contraception (eg, abstinence, IUD or barrier method plus hormonal method)&#xD;
             and having a negative serum beta-HCG result at screening and being willing to remain&#xD;
             on the current form of contraception for the duration of the study. Postmenopausal&#xD;
             women could be included but were to have been amenorrhoeic for at least 12 months to&#xD;
             be considered as not being of child-bearing potential.&#xD;
&#xD;
          3. Fertile men not willing to use reliable contraception or with partners not willing to&#xD;
             use reliable contraception.&#xD;
&#xD;
          4. Patients with status epilepticus within the past 24 months.&#xD;
&#xD;
          5. Patients with unstable abnormalities of the hepatic, renal, cardiovascular,&#xD;
             respiratory, abdominal, haematological, endocrine or metabolic systems which might&#xD;
             complicate assessment of the tolerability of the study medication.&#xD;
&#xD;
          6. Patients with significantly elevated liver enzymes (abnormal bilirubin level, or serum&#xD;
             transaminase levels more than 1.5 times the upper limit of normal).&#xD;
&#xD;
          7. Patients taking drugs other than anti-epileptic agents which induce the enzyme&#xD;
             cytochrome P450 3A4 (since these might reduce the plasma concentration of E2007),&#xD;
             including dexamethasone, rifabutin, rifampacin, St John's Wort.&#xD;
&#xD;
          8. Patients with past or present drug or alcohol abuse.&#xD;
&#xD;
          9. Patients with unstable psychiatric illness.&#xD;
&#xD;
         10. Patients who had received an investigational drug within the three months before&#xD;
             baseline.&#xD;
&#xD;
         11. Patients without a reliable partner or carer.&#xD;
&#xD;
         12. Patients with any condition which would make the patient, in the opinion of the&#xD;
             investigator, unsuitable for the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>3ClinicalResearch AG</name>
      <address>
        <city>Hennigsdorf</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>July 31, 2015</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>December 17, 2018</last_update_submitted>
  <last_update_submitted_qc>December 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Epilepsy</keyword>
  <keyword>E2007</keyword>
  <keyword>partial seizures</keyword>
  <keyword>generalized seizures</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
    <mesh_term>Seizures</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/NCT03780907
org study id: E2007-E049-203
nct id: NCT03780907
lead sponsor: 
has dmc: No
The objectives of this study were to assess the tolerability and safety of E2007 in patients
      with refractory partial or generalised seizures and to assess the pharmacokinetics of E2007
      in epileptic patients receiving at least one concomitant anti-epileptic drug.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of participants with Treatment Emergent Adverse Events (TEAEs)
time frame: From administration of first dose of study drug up until 42 days.
description: The TEAEs were defined as those Adverse Events (AEs) that start on or after the first dose of the treatment until the end of the study. AEs were classified by the investigator as 'not related', 'possibly related' or 'probably related'.
measure: Clinical Global Impression of Tolerability (CGIT)
time frame: Day 28
description: The investigator's global impressions of the tolerability of the study treatment was based on a five point scale: 1 - very good, 2 - good, 3 - moderate, 4 - poor, and 5 - very poor.
measure: Pharmacokinetic Parameter: Area Under the Curve (AUC)(0-24hr) of E2007
time frame: Day 1 and Day 14
description: Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. A measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
measure: Pharmacokinetic Parameter: Cmax (Maximum Observed Plasma Concentration) of E2007
time frame: Day 1 and Day 14
description: Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. The maximum concentration of a drug observed after its administration.
measure: Pharmacokinetic Parameter: Tmax (Time to Maximum Concentration) of E2007
time frame: Day 1 and Day 14
description: Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. The time after dosing when a drug attains its highest measurable concentration (Cmax).
measure: Pharmacokinetic Parameter: Css,min (Minimum Steady State Plasma Concentration) of E2007
time frame: Day 14
description: Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants. Lowest plasma concentration within a steady-state dosing interval.
measure: Pharmacokinetic Parameter: Cav (Average Plasma Concentration) of E2007
time frame: Day 14
description: Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.
measure: Pharmacokinetic Parameter: Peak-to-trough Fluctuation (PTF) of E2007
time frame: Day 14
description: Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.
measure: Pharmacokinetic Parameter: Observed Accumulation Ratio (Rac) of E2007
time frame: Day 14
description: Standard pharmacokinetic parameters for E2007 were derived from plasma drug concentrations in epileptic participants.
measure: Change from Baseline of Bond and Lader Scale
time frame: Baseline, Day 28 and Day 42
description: The Bond and Lader visual analogue mood scale (VAMS) had a score from 0 - 100; a higher score represented worsening of the participants condition attributed to 3 factors, (1) Anxiety (e.g., calmness), (2) Sedation (e.g., alertness, (3) Dysphoria (e.g., contentedness). The change was visit minus baseline.
measure: Change from Baseline of Peak Saccadic Velocity (PSV)
time frame: Baseline, Day 28, Day 42
description: Saccadic velocity is the rate of eye movement in response to stimulus. The saccadic eye movement was used to allow comparison of any sedative effects seen.
measure: Number of Particpants receiving other Anti-epileptic agents During Treatment
time frame: Day 1 and Day 14
measure: Percent Change from Baseline of Failed Saccades
time frame: Baseline, Day 28, Day 42
description: Failed saccades is stimulus resulting in no eye movement above a defined threshold within a specified time.
measure: Mean trough concentrations of E2007
time frame: Day 7, Day 21, and Day 28
measure: Number of seizures
time frame: Baseline (Day-1) to Day 42
measure: The Clinical Global Impression of Change
time frame: Day 28
arm group label: E2007 1 mg
arm group type: Experimental
description: Tablet, once daily to be taken in the morning by mouth, one hour before breakfast, with a glass of water.
arm group label: E2007 2 mg
arm group type: Experimental
description: Tablet, once daily to be taken in the morning by mouth, one hour before breakfast, with a glass of water.
arm group label: Placebo
arm group type: Placebo Comparator
description: Tablet, once daily to be taken in the morning, one hour before breakfast, with a glass of water.
intervention type: Drug
intervention name: E2007
description: 1 mg of E2007 was administered by mouth once daily.
arm group label: E2007 1 mg
intervention type: Drug
intervention name: E2007
description: 2 mg of E2007 was administered by mouth once daily.
arm group label: E2007 2 mg
intervention type: Drug
intervention name: Placebo
description: Placebo once daily of oral tablet formulation to be taken in the morning, one hour before breakfast, with a glass of water.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Epilepsy
mesh term: Seizures