<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/NCT01725529</url>
  </required_header>
  <id_info>
    <org_study_id>CR017962</org_study_id>
    <secondary_id>TMC435HPC3005</secondary_id>
    <nct_id>NCT01725529</nct_id>
  </id_info>
  <brief_title>An Efficacy, Pharmacokinetics, Safety and Tolerability Study of TMC435 as Part of a Treatment Regimen for Hepatitis C-Infected Patients</brief_title>
  <official_title>A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve, Genotype 1 Hepatitis C-Infected Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen R&amp;D Ireland</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen R&amp;D Ireland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to provide confirmatory efficacy and safety data of TMC435 as&#xD;
      part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) in&#xD;
      patients with genotype 1 Hepatitis C virus (HCV) infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, randomized (study drug is assigned by chance), double-blind (neither&#xD;
      sponsor, physician nor patient knows the name of the assigned study drug), Phase III study to&#xD;
      compare the efficacy, tolerability and safety of TMC435 (in development for treatment of&#xD;
      chronic hepatitis C virus [HCV] infection) versus placebo (a preparation containing no drug&#xD;
      used as control) as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a)&#xD;
      and ribavirin (RBV) (both current therapies for HCV) in adult treatment-naïve patients&#xD;
      (patients who have never taken HCV medications) with genotype 1 Hepatitis C virus (HCV)&#xD;
      infection. The study will consist of a screening period with a maximum duration of 6 weeks, a&#xD;
      response guided 24- or 48-week (TMC435 treatment groups) or 48-week (control group) treatment&#xD;
      period, and a post-therapy follow-up period up to 72 weeks after the start of treatment.&#xD;
      Patients will be randomly assigned in a 1:1:1 fashion to receive TMC435 or placebo,&#xD;
      stratified by HCV genotype 1 subtype and IL28B genotype within each country. In the first 24&#xD;
      weeks, patients will receive 12 weeks TMC435 100 or 150 mg or placebo once-daily (q.d.) plus&#xD;
      PegIFNα-2a plus RBV, after which they will continue with PegIFNα-2a and RBV. Response-guided&#xD;
      treatment criteria will be used to determine PegIFNα-2a and RBV total treatment duration of&#xD;
      24 or 48 weeks for patients in the TMC435 treatment groups. In the control group, all&#xD;
      patients will be required to complete 48 weeks of treatment with PegIFNα-2a and RBV. In all 3&#xD;
      treatment groups, there will be a post-therapy follow-up period up to 72 weeks after the&#xD;
      start of treatment. The total study duration for each patient will be a maximum of 78 weeks&#xD;
      (including the 6-week screening period).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)</measure>
    <time_frame>12 weeks after the end of treatment (EOT: Week 24 or 48)</time_frame>
    <description>Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (&lt;) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) undetectable at end of treatment and, 2). the HCV RNA is &lt; LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24)</measure>
    <time_frame>24 weeks after the end of treatment (EOT: Week 24 or 48)</time_frame>
    <description>Participants considered to have achieved SVR24 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (&lt;) lower limit of quantification (LLOQ;25 IU/mL) undetectable at end of treatment and, 2). the HCV RNA is &lt; LLOQ detectable or undetectable at 24 weeks after the planned end of study drug treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72)</measure>
    <time_frame>Week 72</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With On-treatment Failure</measure>
    <time_frame>End of Treatment (EOT: Week 24 or 48)</time_frame>
    <description>A participant with on-treatment failure refers to a participant with confirmed detectable HCV RNA at the end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Viral Breakthrough</measure>
    <time_frame>Week 24 or 48 (End of Treatment)</time_frame>
    <description>The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma. Viral breakthrough was defined as a confirmed increase of &gt;1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of &gt;100 IU/mL in subjects whose HCV RNA levels had previously been below the limit of quantification (&lt;25 IU/mL detectable) or undetectable (&lt;25 IU/mL undetectable) while on study treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Viral Relapse</measure>
    <time_frame>72 weeks after the EOT (Week 24 or 48)</time_frame>
    <description>Viral relapse was defined as undetectable HCV RNA at the actual end of treatment and last HCV RNA measurement during follow-up ≥25 IU/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level</measure>
    <time_frame>72 weeks after the EOT (Week 24 or 48)</time_frame>
    <description>Percentage of participants with on-treatment normalization of alanine aminotransferase level were assessed.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">457</enrollment>
  <condition>Hepatitis C, Chronic</condition>
  <arm_group>
    <arm_group_label>TMC435 150 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive 12 weeks TMC435 150 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue to receive treatment with PegIFNα-2a and RBV until Week 48.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TMC435 100 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive 12 weeks TMC435 100 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue PegIFNα-2a and RBV until Week 48.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TMC435</intervention_name>
    <description>TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12).</description>
    <arm_group_label>TMC435 100 mg</arm_group_label>
    <arm_group_label>TMC435 150 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Peginterferon-alpha (PegIFNα-2a)</intervention_name>
    <description>PegIFNα-2a (180 micrograms [μg] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>TMC435 100 mg</arm_group_label>
    <arm_group_label>TMC435 150 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin (RBV)</intervention_name>
    <description>Ribavirin 1000 or 1200 mg/day (taken as 100 mg or 200 mg tablets) depending on body weight (If body weight is &lt; 75 kg the total daily dose of RBV will be 1000 mg, administered as 400 mg intake with food in the morning and 600 mg intake with food in the evening. If body weight is &gt; or = 75 kg the total daily dose will be 1200 mg, administered as 2 x 600 mg per intake with food, morning and evening) for 24 or 48 weeks.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>TMC435 100 mg</arm_group_label>
    <arm_group_label>TMC435 150 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo capsules taken orally with food once-daily for 48 weeks.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A liver biopsy within 3 years prior to the screening visit (or between screening and&#xD;
             day of randomization) with histology consistent with chronic Hepatitis C virus (HCV)&#xD;
             infection&#xD;
&#xD;
          -  Presence of contraindications for a liver biopsy in patients who are otherwise deemed&#xD;
             eligible for participation does not exclude the patient from participation&#xD;
&#xD;
          -  Genotype 1 HCV infection (confirmed at screening)&#xD;
&#xD;
          -  Plasma HCV RNA of &gt; 10,000 IU/mL at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with any approved or investigational drug for the treatment of&#xD;
             hepatitis C&#xD;
&#xD;
          -  Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen R&amp;D Ireland Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen R&amp;D Ireland</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Changchun</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Changsha</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chengdu</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chongqing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Guangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Harbin</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jinan</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lanzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nanjing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Shenyang</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tianjin</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wuhan</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zhengzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Busan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chuncheon, Gangwon-Do</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gyeongsangnam-Do</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 14, 2012</study_first_posted>
  <results_first_submitted>July 15, 2015</results_first_submitted>
  <results_first_submitted_qc>July 15, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 13, 2015</results_first_posted>
  <last_update_submitted>July 15, 2015</last_update_submitted>
  <last_update_submitted_qc>July 15, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 13, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatitis C, Chronic</keyword>
  <keyword>TMC435</keyword>
  <keyword>Ribavirin</keyword>
  <keyword>peginterferon-alpha (PegIFNα-2a)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ribavirin</mesh_term>
    <mesh_term>Simeprevir</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Simeprevir (TMC435) 100mg</title>
          <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
        </group>
        <group group_id="P3">
          <title>Simeprevir (TMC435) 150mg</title>
          <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="152"/>
                <participants group_id="P2" count="153"/>
                <participants group_id="P3" count="152"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="137"/>
                <participants group_id="P2" count="137"/>
                <participants group_id="P3" count="142"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="10"/>
              </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="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Simeprevir (TMC435) 100mg</title>
          <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
        </group>
        <group group_id="B3">
          <title>Simeprevir (TMC435) 150mg</title>
          <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</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="152"/>
            <count group_id="B2" value="153"/>
            <count group_id="B3" value="152"/>
            <count group_id="B4" value="457"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45" lower_limit="18" upper_limit="68"/>
                    <measurement group_id="B2" value="45" lower_limit="18" upper_limit="68"/>
                    <measurement group_id="B3" value="44" lower_limit="19" upper_limit="68"/>
                    <measurement group_id="B4" value="45" lower_limit="18" upper_limit="68"/>
                  </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="79"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="75"/>
                    <measurement group_id="B4" value="221"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="73"/>
                    <measurement group_id="B2" value="86"/>
                    <measurement group_id="B3" value="77"/>
                    <measurement group_id="B4" value="236"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)</title>
        <description>Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (&lt;) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) undetectable at end of treatment and, 2). the HCV RNA is &lt; LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment.</description>
        <time_frame>12 weeks after the end of treatment (EOT: Week 24 or 48)</time_frame>
        <population>Intent-to-treat (ITT) population included all the randomized participants who took at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Simeprevir (TMC435) 100mg</title>
            <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
          <group group_id="O3">
            <title>Simeprevir (TMC435) 150mg</title>
            <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)</title>
          <description>Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (&lt;) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) undetectable at end of treatment and, 2). the HCV RNA is &lt; LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment.</description>
          <population>Intent-to-treat (ITT) population included all the randomized participants who took at least 1 dose of study drug.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="152"/>
                <count group_id="O2" value="153"/>
                <count group_id="O3" value="152"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.7"/>
                    <measurement group_id="O2" value="88.9"/>
                    <measurement group_id="O3" value="90.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24)</title>
        <description>Participants considered to have achieved SVR24 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (&lt;) lower limit of quantification (LLOQ;25 IU/mL) undetectable at end of treatment and, 2). the HCV RNA is &lt; LLOQ detectable or undetectable at 24 weeks after the planned end of study drug treatment.</description>
        <time_frame>24 weeks after the end of treatment (EOT: Week 24 or 48)</time_frame>
        <population>ITT population included all the randomized participants who took at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Simeprevir (TMC435) 100mg</title>
            <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
          <group group_id="O3">
            <title>Simeprevir (TMC435) 150mg</title>
            <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24)</title>
          <description>Participants considered to have achieved SVR24 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (&lt;) lower limit of quantification (LLOQ;25 IU/mL) undetectable at end of treatment and, 2). the HCV RNA is &lt; LLOQ detectable or undetectable at 24 weeks after the planned end of study drug treatment.</description>
          <population>ITT population included all the randomized participants who took at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="152"/>
                <count group_id="O2" value="153"/>
                <count group_id="O3" value="152"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.0"/>
                    <measurement group_id="O2" value="88.9"/>
                    <measurement group_id="O3" value="90.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72)</title>
        <time_frame>Week 72</time_frame>
        <population>ITT population included all the randomized participants who took at least 1 dose of study drug. 'N' (number of participants analyzed) signifies those participants who were analyzed for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Simeprevir (TMC435) 100mg</title>
            <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
          <group group_id="O3">
            <title>Simeprevir (TMC435) 150mg</title>
            <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72)</title>
          <population>ITT population included all the randomized participants who took at least 1 dose of study drug. 'N' (number of participants analyzed) signifies those participants who were analyzed for this measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="152"/>
                <count group_id="O2" value="153"/>
                <count group_id="O3" value="152"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.0"/>
                    <measurement group_id="O2" value="87.6"/>
                    <measurement group_id="O3" value="90.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With On-treatment Failure</title>
        <description>A participant with on-treatment failure refers to a participant with confirmed detectable HCV RNA at the end of treatment.</description>
        <time_frame>End of Treatment (EOT: Week 24 or 48)</time_frame>
        <population>ITT population included all the randomized participants who took at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Simeprevir (TMC435) 100mg</title>
            <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
          <group group_id="O3">
            <title>Simeprevir (TMC435) 150mg</title>
            <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With On-treatment Failure</title>
          <description>A participant with on-treatment failure refers to a participant with confirmed detectable HCV RNA at the end of treatment.</description>
          <population>ITT population included all the randomized participants who took at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="152"/>
                <count group_id="O2" value="153"/>
                <count group_id="O3" value="152"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.5"/>
                    <measurement group_id="O2" value="3.3"/>
                    <measurement group_id="O3" value="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Viral Breakthrough</title>
        <description>The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma. Viral breakthrough was defined as a confirmed increase of &gt;1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of &gt;100 IU/mL in subjects whose HCV RNA levels had previously been below the limit of quantification (&lt;25 IU/mL detectable) or undetectable (&lt;25 IU/mL undetectable) while on study treatment.</description>
        <time_frame>Week 24 or 48 (End of Treatment)</time_frame>
        <population>ITT population included all the randomized participants who took at least 1 dose of study drug. 'N' (number of participants analyzed) signifies those participants who were analyzed for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Simeprevir (TMC435) 100mg</title>
            <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
          <group group_id="O3">
            <title>Simeprevir (TMC435) 150mg</title>
            <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Viral Breakthrough</title>
          <description>The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma. Viral breakthrough was defined as a confirmed increase of &gt;1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of &gt;100 IU/mL in subjects whose HCV RNA levels had previously been below the limit of quantification (&lt;25 IU/mL detectable) or undetectable (&lt;25 IU/mL undetectable) while on study treatment.</description>
          <population>ITT population included all the randomized participants who took at least 1 dose of study drug. 'N' (number of participants analyzed) signifies those participants who were analyzed for this measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="152"/>
                <count group_id="O2" value="153"/>
                <count group_id="O3" value="151"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                    <measurement group_id="O2" value="2.6"/>
                    <measurement group_id="O3" value="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Viral Relapse</title>
        <description>Viral relapse was defined as undetectable HCV RNA at the actual end of treatment and last HCV RNA measurement during follow-up ≥25 IU/mL.</description>
        <time_frame>72 weeks after the EOT (Week 24 or 48)</time_frame>
        <population>ITT population included all the randomized participants who took at least 1 dose of study drug. 'N' (number of participants analyzed) signifies those participants who were analyzed for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Simeprevir (TMC435) 100mg</title>
            <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
          <group group_id="O3">
            <title>Simeprevir (TMC435) 150mg</title>
            <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Viral Relapse</title>
          <description>Viral relapse was defined as undetectable HCV RNA at the actual end of treatment and last HCV RNA measurement during follow-up ≥25 IU/mL.</description>
          <population>ITT population included all the randomized participants who took at least 1 dose of study drug. 'N' (number of participants analyzed) signifies those participants who were analyzed for this measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="131"/>
                <count group_id="O2" value="142"/>
                <count group_id="O3" value="141"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5"/>
                    <measurement group_id="O2" value="1.4"/>
                    <measurement group_id="O3" value="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level</title>
        <description>Percentage of participants with on-treatment normalization of alanine aminotransferase level were assessed.</description>
        <time_frame>72 weeks after the EOT (Week 24 or 48)</time_frame>
        <population>ITT population included all the randomized participants who took at least 1 dose of study drug. 'N' (number of participants analyzed) signifies those participants who were analyzed for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Simeprevir (TMC435) 100mg</title>
            <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
          <group group_id="O3">
            <title>Simeprevir (TMC435) 150mg</title>
            <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level</title>
          <description>Percentage of participants with on-treatment normalization of alanine aminotransferase level were assessed.</description>
          <population>ITT population included all the randomized participants who took at least 1 dose of study drug. 'N' (number of participants analyzed) signifies those participants who were analyzed for this measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="91"/>
                <count group_id="O2" value="79"/>
                <count group_id="O3" value="89"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.7"/>
                    <measurement group_id="O2" value="86.1"/>
                    <measurement group_id="O3" value="89.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>up to 4 weeks after End of treatment (EOT: Week 24 or Week 48)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received placebo matching to TMC435 100 milligram (mg) and TMC435 150 mg for 12 weeks once daily (q.d.) plus peginterferon-alpha (PegIFNa-2a) and ribavirin (RBV) for 48 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Simeprevir (TMC435) 100mg</title>
          <description>Participants received TMC435 100 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 150 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
        </group>
        <group group_id="E3">
          <title>Simeprevir (TMC435) 150mg</title>
          <description>Participants received TMC435 150 mg once daily (q.d.) for 12 weeks plus peginterferon-alpha (PegIFNα-2a), ribavirin (RBV) and Placebo matching to TMC435 100 mg, followed by PegIFNα-2a and RBV alone. Response-guided treatment criterion was used to determine total treatment duration of 24 or 48 weeks for participants in the TMC435 treatment groups.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 15.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis ischaemic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Incision site infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Atypical pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Chronic hepatitis C</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Pulmonary tuberculosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Meniscus lesion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Multiple injuries</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Tibia fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Traumatic lung injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Cholesterosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Undifferentiated connective tissue disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Brain neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Ureteric stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Shock haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA Version 15.1</default_vocab>
        <default_assessment>Non-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="149" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="149" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="149" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="53" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="44" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="31" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="38" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="28" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="94" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="87" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="84" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="81" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="77" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="80" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="57" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="73" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="57" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="46" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="47" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="31" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="54" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Bilirubin conjugated increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="33" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Red blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="18" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Haematocrit decreased</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Blood bilirubin unconjugated increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Monocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Blood calcium decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Neutrophil percentage decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Low density lipoprotein decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Mean cell haemoglobin concentration decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Mean cell volume increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Blood cholesterol decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Blood potassium decreased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="152"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="153"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="152"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>ASSOCIATE DIRECTOR, MEDICAL DEPARTMENT</name_or_title>
      <organization>Janssen R&amp;D US</organization>
      <email>ClinicalTrialDisclosure@its.jnj.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/NCT01725529
org study id: CR017962
secondary id: TMC435HPC3005
nct id: NCT01725529
lead sponsor: 
has dmc: Yes
The purpose of this study is to provide confirmatory efficacy and safety data of TMC435 as
      part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) in
      patients with genotype 1 Hepatitis C virus (HCV) infection.
This is a multicenter, randomized (study drug is assigned by chance), double-blind (neither
      sponsor, physician nor patient knows the name of the assigned study drug), Phase III study to
      compare the efficacy, tolerability and safety of TMC435 (in development for treatment of
      chronic hepatitis C virus [HCV] infection) versus placebo (a preparation containing no drug
      used as control) as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a)
      and ribavirin (RBV) (both current therapies for HCV) in adult treatment-naïve patients
      (patients who have never taken HCV medications) with genotype 1 Hepatitis C virus (HCV)
      infection. The study will consist of a screening period with a maximum duration of 6 weeks, a
      response guided 24- or 48-week (TMC435 treatment groups) or 48-week (control group) treatment
      period, and a post-therapy follow-up period up to 72 weeks after the start of treatment.
      Patients will be randomly assigned in a 1:1:1 fashion to receive TMC435 or placebo,
      stratified by HCV genotype 1 subtype and IL28B genotype within each country. In the first 24
      weeks, patients will receive 12 weeks TMC435 100 or 150 mg or placebo once-daily (q.d.) plus
      PegIFNα-2a plus RBV, after which they will continue with PegIFNα-2a and RBV. Response-guided
      treatment criteria will be used to determine PegIFNα-2a and RBV total treatment duration of
      24 or 48 weeks for patients in the TMC435 treatment groups. In the control group, all
      patients will be required to complete 48 weeks of treatment with PegIFNα-2a and RBV. In all 3
      treatment groups, there will be a post-therapy follow-up period up to 72 weeks after the
      start of treatment. The total study duration for each patient will be a maximum of 78 weeks
      (including the 6-week screening period).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
time frame: 12 weeks after the end of treatment (EOT: Week 24 or 48)
description: Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) undetectable at end of treatment and, 2). the HCV RNA is < LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment.
measure: Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24)
time frame: 24 weeks after the end of treatment (EOT: Week 24 or 48)
description: Participants considered to have achieved SVR24 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ;25 IU/mL) undetectable at end of treatment and, 2). the HCV RNA is < LLOQ detectable or undetectable at 24 weeks after the planned end of study drug treatment.
measure: Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72)
time frame: Week 72
measure: Percentage of Participants With On-treatment Failure
time frame: End of Treatment (EOT: Week 24 or 48)
description: A participant with on-treatment failure refers to a participant with confirmed detectable HCV RNA at the end of treatment.
measure: Percentage of Participants With Viral Breakthrough
time frame: Week 24 or 48 (End of Treatment)
description: The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma. Viral breakthrough was defined as a confirmed increase of >1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of >100 IU/mL in subjects whose HCV RNA levels had previously been below the limit of quantification (<25 IU/mL detectable) or undetectable (<25 IU/mL undetectable) while on study treatment.
measure: Percentage of Participants With Viral Relapse
time frame: 72 weeks after the EOT (Week 24 or 48)
description: Viral relapse was defined as undetectable HCV RNA at the actual end of treatment and last HCV RNA measurement during follow-up ≥25 IU/mL.
measure: Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level
time frame: 72 weeks after the EOT (Week 24 or 48)
description: Percentage of participants with on-treatment normalization of alanine aminotransferase level were assessed.
arm group label: TMC435 150 mg
arm group type: Experimental
description: Patients will receive 12 weeks TMC435 150 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue to receive treatment with PegIFNα-2a and RBV until Week 48.
arm group label: TMC435 100 mg
arm group type: Experimental
description: Patients will receive 12 weeks TMC435 100 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue PegIFNα-2a and RBV until Week 48.
arm group label: Control
arm group type: Placebo Comparator
description: Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks.
intervention type: Drug
intervention name: TMC435
description: TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12).
arm group label: TMC435 100 mg
arm group label: TMC435 150 mg
intervention type: Drug
intervention name: Peginterferon-alpha (PegIFNα-2a)
description: PegIFNα-2a (180 micrograms [μg] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks.
arm group label: Control
arm group label: TMC435 100 mg
arm group label: TMC435 150 mg
intervention type: Drug
intervention name: Ribavirin (RBV)
description: Ribavirin 1000 or 1200 mg/day (taken as 100 mg or 200 mg tablets) depending on body weight (If body weight is < 75 kg the total daily dose of RBV will be 1000 mg, administered as 400 mg intake with food in the morning and 600 mg intake with food in the evening. If body weight is > or = 75 kg the total daily dose will be 1200 mg, administered as 2 x 600 mg per intake with food, morning and evening) for 24 or 48 weeks.
arm group label: Control
arm group label: TMC435 100 mg
arm group label: TMC435 150 mg
intervention type: Drug
intervention name: Placebo
description: Matching placebo capsules taken orally with food once-daily for 48 weeks.
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Janssen R&D Ireland Clinical Trial
role: Study Director
affiliation: Janssen R&D Ireland
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country: China
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis
mesh term: Ribavirin
mesh term: Simeprevir
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 