<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/NCT01679002</url>
  </required_header>
  <id_info>
    <org_study_id>BIA-2093-110</org_study_id>
    <nct_id>NCT01679002</nct_id>
  </id_info>
  <brief_title>Steady-state Pharmacokinetics of BIA 2-093 and Oxcarbazepine in Healthy Volunteers</brief_title>
  <official_title>Steady-state Pharmacokinetics of BIA 2-093 and Oxcarbazepine in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bial - Portela C S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bial - Portela C S.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To investigate the steady-state pharmacokinetics of once-daily and twice-daily regimens of&#xD;
      BIA 2-093 and twice-daily regimen of Oxcarbazepine (Trileptal®) in healthy subjects and to&#xD;
      assess the tolerability of such regimens in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers.&#xD;
      The study consisted of three 8-day treatment periods separated by washout periods of 10-15&#xD;
      days. On each of the treatment periods the volunteers received either a daily oral dose of&#xD;
      BIA 2-093 900 mg once-daily (od), BIA 2-093 450 mg twice-daily (bid), or Oxcarbazepine&#xD;
      (Trileptal®) 450 mg bid.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2003</start_date>
  <completion_date type="Actual">December 2003</completion_date>
  <primary_completion_date type="Actual">December 2003</primary_completion_date>
  <phase>Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax - Maximum Observed Plasma Drug Concentration</measure>
    <time_frame>pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose</time_frame>
    <description>Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites:&#xD;
BIA 2-194 BIA 2-195 Oxcarbazepine</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC - Area Under the Plasma Concentration Versus Time Curve</measure>
    <time_frame>pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose</time_frame>
    <description>AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites:&#xD;
BIA 2-194 BIA 2-195 Oxcarbazepine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of of Subjects Reporting at Least One Adverse Event</measure>
    <time_frame>8 weeks</time_frame>
    <description>Number of of subjects reporting at least one adverse event.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Epilepsy</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period&#xD;
BIA 2-093 450 mg od - BIA 2-093 450 mg bid - OXC 900 mg bid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period&#xD;
BIA 2-093 450 mg bid - OXC 450 mg bid - BIA 2-093 900 mg od</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period&#xD;
OXC 450 mg bid - BIA 2-093 900 mg od - BIA 2-093 450 mg bid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIA 2-093</intervention_name>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_label>Group C</arm_group_label>
    <other_name>ESL, Eslicarbazepine acetate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxcarbazepine</intervention_name>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_label>Group C</arm_group_label>
    <other_name>OXC, Trileptal®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects were eligible for entry into the study if they fulfilled the following&#xD;
             inclusion criteria:&#xD;
&#xD;
          -  Male or female subjects aged between 18 and 45 years, inclusive.&#xD;
&#xD;
          -  Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive.&#xD;
&#xD;
          -  Subjects who were healthy as determined by pre-study medical history, physical&#xD;
             examination, neurological examination, and 12-lead ECG.&#xD;
&#xD;
          -  Subjects who had clinical laboratory tests clinically acceptable.&#xD;
&#xD;
          -  Subjects who were negative for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab tests at&#xD;
             screening.&#xD;
&#xD;
          -  Subjects who were negative for alcohol and drugs of abuse at screening and first&#xD;
             admission.&#xD;
&#xD;
          -  Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per&#xD;
             day.&#xD;
&#xD;
          -  Subjects who were able and willing to give written informed consent.&#xD;
&#xD;
          -  If case of female subjects, subjects who were not of childbearing potential by reason&#xD;
             of surgery or, if of childbearing potential, who used one of the following methods of&#xD;
             contraception: double-barrier, intrauterine device or abstinence.&#xD;
&#xD;
          -  If case of female subjects, subjects who had a negative pregnancy test at screening&#xD;
             and first admission.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who did not conform to the above inclusion criteria.&#xD;
&#xD;
          -  Subjects who had a clinically relevant history or presence of respiratory,&#xD;
             gastrointestinal, renal, hepatic, haematological, lymphatic, neurological,&#xD;
             cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological,&#xD;
             dermatological, endocrine, connective tissue diseases or disorders.&#xD;
&#xD;
          -  Subjects who had a clinically relevant surgical history.&#xD;
&#xD;
          -  Subjects who had a clinically relevant family history.&#xD;
&#xD;
          -  Subjects who had a history of relevant atopy.&#xD;
&#xD;
          -  Subjects who had a history of hypersensitivity to carbamazepine or oxcarbazepine or&#xD;
             any other relevant drug hypersensitivity.&#xD;
&#xD;
          -  Subjects who had a history of alcoholism or drug abuse.&#xD;
&#xD;
          -  Subjects who consumed more than 14 units of alcohol a week.&#xD;
&#xD;
          -  Subjects who had a significant infection or known inflammatory process on screening&#xD;
             and/or first admission.&#xD;
&#xD;
          -  Subjects who had acute gastrointestinal symptoms at the time of screening and/or first&#xD;
             admission (e.g., nausea, vomiting, diarrhoea, heartburn).&#xD;
&#xD;
          -  Subjects who had used prescription or over-the-counter medication within two weeks of&#xD;
             first admission.&#xD;
&#xD;
          -  Subjects who had used any investigational drug and/or participated in any clinical&#xD;
             trial within four months of their first admission.&#xD;
&#xD;
          -  Subjects who had previously received BIA 2-093.&#xD;
&#xD;
          -  Subjects who had donated and/or received any blood or blood products within the&#xD;
             previous 4 months prior to screening.&#xD;
&#xD;
          -  Subjects who were vegetarians, vegans and/or have medical dietary restrictions.&#xD;
&#xD;
          -  Subjects who could not communicate reliably with the investigator.&#xD;
&#xD;
          -  Subjects who were unlikely to co-operate with the requirements of the study.&#xD;
&#xD;
          -  Subjects who were unwilling or unable to give written informed consent.&#xD;
&#xD;
          -  In case of female subjects, subjects who were pregnant or breast-feeding.&#xD;
&#xD;
          -  In case of female subjects, subjects who were of childbearing potential and did not&#xD;
             use an approved effective contraceptive method or used oral contraceptives.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Manuel Vaz-da-Silva, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BIAL - Portela &amp; Cª S.A.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>BIAL - Portela &amp; Cª S.A. - Human Pharmacology Unit (UFH)</name>
      <address>
        <city>S. Mamede do Coronado</city>
        <state>Trofa</state>
        <zip>4745-457</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Portugal</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <results_first_submitted>November 28, 2014</results_first_submitted>
  <results_first_submitted_qc>December 31, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 1, 2015</results_first_posted>
  <last_update_submitted>December 31, 2014</last_update_submitted>
  <last_update_submitted_qc>December 31, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 1, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Epilepsy</keyword>
  <keyword>Oxcarbazepine</keyword>
  <keyword>Eslicarbazepine Acetate</keyword>
  <keyword>BIA 2-093</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eslicarbazepine acetate</mesh_term>
    <mesh_term>Oxcarbazepine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Group A</title>
          <description>BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period.&#xD;
BIA 2-093 900 mg od - BIA 2-093 450 mg bid - OXC 450 mg bid</description>
        </group>
        <group group_id="P2">
          <title>Group B</title>
          <description>BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period&#xD;
BIA 2-093 450 mg bid OXC 450 mg bid BIA 2-093 900 mg od</description>
        </group>
        <group group_id="P3">
          <title>Group C</title>
          <description>oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period OXC 450 mg bid - BIA 2-093 900 mg od - BIA 2-093 450 mg bid</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>BIA 2-093 900 mg Once-daily Period</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>BIA 2-093 450 mg Twice-daily Period</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Oxcarbazepine 450 mg Twice-daily Period</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group A</title>
          <description>BIA 2-093 450 mg once-daily period followed by BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period BIA 2-093 450 mg od - BIA 2-093 450 mg bid - OXC 450 mg bid</description>
        </group>
        <group group_id="B2">
          <title>Group B</title>
          <description>BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 450 mg once-daily period BIA 2-093 450 mg bid - OXC 450 mg bid - BIA 2-093 450 mg od</description>
        </group>
        <group group_id="B3">
          <title>Group C</title>
          <description>oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 450 mg once-daily period followed by BIA 2-093 450 mg twice-daily period OXC 450 mg bid - BIA 2-093 450 mg od - BIA 2-093 450 mg bid</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cmax - Maximum Observed Plasma Drug Concentration</title>
        <description>Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites:&#xD;
BIA 2-194 BIA 2-195 Oxcarbazepine</description>
        <time_frame>pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose</time_frame>
        <population>The results are related to overall population in the study devided by period of treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>BIA 2-093 900 mg od</title>
            <description>ESL, Eslicarbazepine acetate BIA 2-093 900 mg od</description>
          </group>
          <group group_id="O2">
            <title>BIA 2-093 450 mg Bid</title>
            <description>ESL, Eslicarbazepine acetate BIA 2-093 450 mg bid</description>
          </group>
          <group group_id="O3">
            <title>Oxcarbazepine 450 mg Bid</title>
            <description>OXC, Oxcarbazepine 450 mg bid</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax - Maximum Observed Plasma Drug Concentration</title>
          <description>Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites:&#xD;
BIA 2-194 BIA 2-195 Oxcarbazepine</description>
          <population>The results are related to overall population in the study devided by period of treatment.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cmax (BIA 2-194)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22210" spread="7257"/>
                    <measurement group_id="O2" value="16667" spread="3981"/>
                    <measurement group_id="O3" value="12195" spread="2053"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmax (BIA 2-195)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="685" spread="188"/>
                    <measurement group_id="O2" value="702" spread="182"/>
                    <measurement group_id="O3" value="2481" spread="362"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmax (Oxcarbazepine)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="208" spread="53.2"/>
                    <measurement group_id="O2" value="182" spread="47.2"/>
                    <measurement group_id="O3" value="1080" spread="548"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC - Area Under the Plasma Concentration Versus Time Curve</title>
        <description>AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites:&#xD;
BIA 2-194 BIA 2-195 Oxcarbazepine</description>
        <time_frame>pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose</time_frame>
        <population>The results are related to overall population in the study devided by period of treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>BIA 2-093 900 mg od</title>
            <description>ESL, Eslicarbazepine acetate BIA 2-093 900 mg od</description>
          </group>
          <group group_id="O2">
            <title>BIA 2-093 450 mg Bid</title>
            <description>ESL, Eslicarbazepine acetate BIA 2-093 450 mg bid</description>
          </group>
          <group group_id="O3">
            <title>Oxcarbazepine 450 mg Bid</title>
            <description>OXC, Oxcarbazepine 450 mg bid</description>
          </group>
        </group_list>
        <measure>
          <title>AUC - Area Under the Plasma Concentration Versus Time Curve</title>
          <description>AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites:&#xD;
BIA 2-194 BIA 2-195 Oxcarbazepine</description>
          <population>The results are related to overall population in the study devided by period of treatment.</population>
          <units>ng*h/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUC0-t (BIA 2-194)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="381601" spread="95368"/>
                    <measurement group_id="O2" value="283014" spread="74203"/>
                    <measurement group_id="O3" value="268376" spread="43294"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC0-t (BIA 2-195)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20164" spread="6790"/>
                    <measurement group_id="O2" value="19091" spread="6042"/>
                    <measurement group_id="O3" value="48841" spread="9041"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC0-t (Oxcarbazepine)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3238" spread="1033"/>
                    <measurement group_id="O2" value="2699" spread="909"/>
                    <measurement group_id="O3" value="5196" spread="1472"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of of Subjects Reporting at Least One Adverse Event</title>
        <description>Number of of subjects reporting at least one adverse event.</description>
        <time_frame>8 weeks</time_frame>
        <population>The results are related to overall population in the study devided by period of treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>BIA 2-093 900 mg od</title>
            <description>ESL, Eslicarbazepine acetate BIA 2-093 900 mg od</description>
          </group>
          <group group_id="O2">
            <title>BIA 2-093 450 mg Bid</title>
            <description>ESL, Eslicarbazepine acetate BIA 2-093 450 mg bid</description>
          </group>
          <group group_id="O3">
            <title>Oxcarbazepine 450 mg Bid</title>
            <description>OXC, Oxcarbazepine 450 mg bid</description>
          </group>
        </group_list>
        <measure>
          <title>Number of of Subjects Reporting at Least One Adverse Event</title>
          <description>Number of of subjects reporting at least one adverse event.</description>
          <population>The results are related to overall population in the study devided by period of treatment.</population>
          <units>Number of of subjects reporting at least</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>BIA 2-093 900 mg</title>
          <description>ESL, Eslicarbazepine acetate BIA 2-093 900 mg od</description>
        </group>
        <group group_id="E2">
          <title>BIA 2-093 450 mg Bid</title>
          <description>ESL, Eslicarbazepine acetate BIA 2-093 450 mg bid</description>
        </group>
        <group group_id="E3">
          <title>Oxcarbazepine 450 mg Bid</title>
          <description>OXC, Oxcarbazepine 450 mg bid</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (7.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Abdominal colic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dry lips</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Epigastric pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Heartburn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Loose stools</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Right upper quadrant pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tooth pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Injection site haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Appetite lost</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Muscle pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Frontal headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nystagmus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Orthostatic dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cervical radiculopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Concentration impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Motor dysfunction NOS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Numbness of limbs</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Occipital headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vasovagal reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Increased libido</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ejaculation disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Erection increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Diffuse macular rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Clinical Research</name_or_title>
      <organization>Bial - Portela &amp; Cª, S.A.</organization>
      <phone>+351 229 866 100</phone>
      <email>jose.rocha@bial.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01679002
org study id: BIA-2093-110
nct id: NCT01679002
lead sponsor: 
has dmc: No
To investigate the steady-state pharmacokinetics of once-daily and twice-daily regimens of
      BIA 2-093 and twice-daily regimen of Oxcarbazepine (Trileptal®) in healthy subjects and to
      assess the tolerability of such regimens in healthy subjects.
Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers.
      The study consisted of three 8-day treatment periods separated by washout periods of 10-15
      days. On each of the treatment periods the volunteers received either a daily oral dose of
      BIA 2-093 900 mg once-daily (od), BIA 2-093 450 mg twice-daily (bid), or Oxcarbazepine
      (Trileptal®) 450 mg bid.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cmax - Maximum Observed Plasma Drug Concentration
time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose
description: Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites:
BIA 2-194 BIA 2-195 Oxcarbazepine
measure: AUC - Area Under the Plasma Concentration Versus Time Curve
time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose
description: AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites:
BIA 2-194 BIA 2-195 Oxcarbazepine
measure: Number of of Subjects Reporting at Least One Adverse Event
time frame: 8 weeks
description: Number of of subjects reporting at least one adverse event.
arm group label: Group A
arm group type: Experimental
description: BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period
BIA 2-093 450 mg od - BIA 2-093 450 mg bid - OXC 900 mg bid
arm group label: Group B
arm group type: Experimental
description: BIA 2-093 450 mg twice-daily period followed by oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period
BIA 2-093 450 mg bid - OXC 450 mg bid - BIA 2-093 900 mg od
arm group label: Group C
arm group type: Experimental
description: oxcarbazepine 450 mg twice-daily period followed by BIA 2-093 900 mg once-daily period followed by BIA 2-093 450 mg twice-daily period
OXC 450 mg bid - BIA 2-093 900 mg od - BIA 2-093 450 mg bid
intervention type: Drug
intervention name: BIA 2-093
arm group label: Group A
arm group label: Group B
arm group label: Group C
other name: ESL, Eslicarbazepine acetate
intervention type: Drug
intervention name: Oxcarbazepine
arm group label: Group A
arm group label: Group B
arm group label: Group C
other name: OXC, Trileptal®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Manuel Vaz-da-Silva, MD, PhD
role: Principal Investigator
affiliation: BIAL - Portela & Cª S.A.
facility: 
country: Portugal
responsible party type: Sponsor
mesh term: Epilepsy
mesh term: Eslicarbazepine acetate
mesh term: Oxcarbazepine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 