<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/NCT02187107</url>
  </required_header>
  <id_info>
    <org_study_id>CR005848</org_study_id>
    <secondary_id>TMC114-C208</secondary_id>
    <nct_id>NCT02187107</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Long-term Safety and Tolerability of TMC114/Rtv in HIV-1 Infected Participants After Rolling-over From Other TMC114 Trials</brief_title>
  <official_title>An Open Label Trial of TMC114/Rtv in HIV-1 Infected Subjects Who Were Randomized in the Trials TMC114-C201, TMC114-C207 or in Sponsor Selected Phase I Trials</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tibotec Pharmaceuticals, Ireland</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tibotec Pharmaceuticals, Ireland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study was primarily to assess the long-term safety and tolerability of&#xD;
      TMC114/rtv in addition to an individually optimized background antiretroviral therapy in&#xD;
      HIV-1 infected participants. In addition, antiviral activity and immunological effect were&#xD;
      also evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a phase II, open label, multicenter trial of an investigational protease inhibitor&#xD;
      TMC114 in the presence of ritonavir (rtv) in HIV-1 infected participants who were randomized&#xD;
      in trials TMC114-C201, TMC114-C207 or in sponsor selected phase I trials and who might derive&#xD;
      benefit from TMC114 therapy, as judged by the investigator.&#xD;
&#xD;
      The trial consisted of a screening period of a maximum of 4 weeks, a 96-week treatment period&#xD;
      and a 4-week follow-up period. The maximal trial duration for each participant was104 weeks.&#xD;
      During the treatment period, all participants were receiving TMC114 in combination with RTV,&#xD;
      orally, as 600/100 mg dose twice daily, in addition to an individually optimized background&#xD;
      regimen of antiretroviral (ARV) therapy, selected by the investigator at a baseline of the&#xD;
      study.&#xD;
&#xD;
      Sponsor provided a follow-up treatment with TMC114 for all participants who continued to&#xD;
      benefit from treatment with TMC114/RTV until it became commercially available for the&#xD;
      participant. Participants, who completed the 96 weeks of treatment period with TMC114, had&#xD;
      the opportunity to roll over to the extension of this trial, if TMC114 was not locally&#xD;
      commercially available.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2005</start_date>
  <completion_date type="Actual">March 2009</completion_date>
  <primary_completion_date type="Actual">September 2005</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events as a measure of safety and tolerability of TMC114/RTV 600/100 mg combination</measure>
    <time_frame>Baseline, up to the end of follow-up period (approximatelly 100 weeks)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with HIV-1 plasma viral load level &lt;50 copies/mL (TLOVR, non-VF censored)</measure>
    <time_frame>Week 48, Week 96</time_frame>
    <description>The Time to Loss of Virologic Response (TLOVR) algorithm will be used to derive response. Response will be confirmed at 2 consecutive visits and participants who discontinue will be considered nonresponders after discontinuation. Resuppression after confirmed virologic failure will be considered as failure. Virologic Failure will include participants who are rebounders (ie, confirmed viral load &gt;= 50 copies/mL after being a responder) or who were never suppressed (no confirmed viral load &lt;50 copies/mL); non-VF censored: participants who discontinue treatment due to reason other than Virologic Failure will be excluded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CD4 cells absolute count</measure>
    <time_frame>Week 48, Week 96</time_frame>
    <description>The immunologic change will be determined by changes in absolute values for CD4 cells.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>TMC114 + rtv</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Every participant recieves 2 tablets of TMC114, 300 mg, combined with one tablet of rtv (ritonavir), 100mg, orally twice daily, every 12 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TMC114</intervention_name>
    <description>300 mg tablets of TMC114 ethanolate with microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, and Opadry® Orange</description>
    <arm_group_label>TMC114 + rtv</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rtv</intervention_name>
    <description>100 mg tablet of Norvir®</description>
    <arm_group_label>TMC114 + rtv</arm_group_label>
    <other_name>Norvir</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Must be diagnosed with HIV&#xD;
&#xD;
          -  Previously randomized in trials TMC114-C201, TMC114-C207 or in sponsor selected Phase&#xD;
             I trials&#xD;
&#xD;
          -  Agreed to take at least 2 antiretroviral agents from baseline onwards&#xD;
&#xD;
          -  Could comply with the protocol requirements&#xD;
&#xD;
          -  General medical condition, in the investigator's opinion, was not interfering with the&#xD;
             assessments and the conduct of the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A disallowed concomitant therapy&#xD;
&#xD;
          -  Current or past history of active alcohol and/or drug use&#xD;
&#xD;
          -  Pregnant or breast-feeding females&#xD;
&#xD;
          -  Any active or unstable medical condition (e.g., tuberculosis; cardiac dysfunction;&#xD;
             pancreatitis; acute viral infections)&#xD;
&#xD;
          -  Clinical or laboratory evidence of active liver disease, liver impairment/dysfunction&#xD;
             or cirrhosis&#xD;
&#xD;
          -  Clinically significant allergy or hypersensitivity to any of the excipients of the&#xD;
             investigational medication&#xD;
&#xD;
          -  Laboratory abnormalities at screening (criteria variable according to the test)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tibotec Pharmaceuticals Limited, Ireland Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Tibotec Pharmaceuticals, Ireland</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Darlinghurst</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wien</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hannover</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Munich</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Szczecin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Denmark</country>
    <country>Germany</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&amp;studyid=1455&amp;filename=CR005848_CSR.pdf</url>
    <description>An Open Label Trial of TMC114/Rtv in HIV-1 Infected Subjects Who Were Randomized in the Trials TMC114-C201, TMC114-C207 or in Sponsor Selected Phase I Trials</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>February 25, 2014</study_first_submitted>
  <study_first_submitted_qc>July 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>August 22, 2014</last_update_submitted>
  <last_update_submitted_qc>August 22, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>AIDS</keyword>
  <keyword>TMC114</keyword>
  <keyword>Ritonavir</keyword>
  <keyword>Norvir</keyword>
  <keyword>Darunavir</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Darunavir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02187107
org study id: CR005848
secondary id: TMC114-C208
nct id: NCT02187107
lead sponsor: 
has dmc: No
The purpose of this study was primarily to assess the long-term safety and tolerability of
      TMC114/rtv in addition to an individually optimized background antiretroviral therapy in
      HIV-1 infected participants. In addition, antiviral activity and immunological effect were
      also evaluated.
This was a phase II, open label, multicenter trial of an investigational protease inhibitor
      TMC114 in the presence of ritonavir (rtv) in HIV-1 infected participants who were randomized
      in trials TMC114-C201, TMC114-C207 or in sponsor selected phase I trials and who might derive
      benefit from TMC114 therapy, as judged by the investigator.

      The trial consisted of a screening period of a maximum of 4 weeks, a 96-week treatment period
      and a 4-week follow-up period. The maximal trial duration for each participant was104 weeks.
      During the treatment period, all participants were receiving TMC114 in combination with RTV,
      orally, as 600/100 mg dose twice daily, in addition to an individually optimized background
      regimen of antiretroviral (ARV) therapy, selected by the investigator at a baseline of the
      study.

      Sponsor provided a follow-up treatment with TMC114 for all participants who continued to
      benefit from treatment with TMC114/RTV until it became commercially available for the
      participant. Participants, who completed the 96 weeks of treatment period with TMC114, had
      the opportunity to roll over to the extension of this trial, if TMC114 was not locally
      commercially available.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events as a measure of safety and tolerability of TMC114/RTV 600/100 mg combination
time frame: Baseline, up to the end of follow-up period (approximatelly 100 weeks)
measure: Number of patients with HIV-1 plasma viral load level <50 copies/mL (TLOVR, non-VF censored)
time frame: Week 48, Week 96
description: The Time to Loss of Virologic Response (TLOVR) algorithm will be used to derive response. Response will be confirmed at 2 consecutive visits and participants who discontinue will be considered nonresponders after discontinuation. Resuppression after confirmed virologic failure will be considered as failure. Virologic Failure will include participants who are rebounders (ie, confirmed viral load >= 50 copies/mL after being a responder) or who were never suppressed (no confirmed viral load <50 copies/mL); non-VF censored: participants who discontinue treatment due to reason other than Virologic Failure will be excluded.
measure: Change in CD4 cells absolute count
time frame: Week 48, Week 96
description: The immunologic change will be determined by changes in absolute values for CD4 cells.
arm group label: TMC114 + rtv
arm group type: Experimental
description: Every participant recieves 2 tablets of TMC114, 300 mg, combined with one tablet of rtv (ritonavir), 100mg, orally twice daily, every 12 hours
intervention type: Drug
intervention name: TMC114
description: 300 mg tablets of TMC114 ethanolate with microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, and Opadry® Orange
arm group label: TMC114 + rtv
intervention type: Drug
intervention name: rtv
description: 100 mg tablet of Norvir®
arm group label: TMC114 + rtv
other name: Norvir
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tibotec Pharmaceuticals Limited, Ireland Clinical Trial
role: Study Director
affiliation: Tibotec Pharmaceuticals, Ireland
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Austria
country: Belgium
country: Denmark
country: Germany
country: Poland
country: Russian Federation
country: United Kingdom
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=1455&filename=CR005848_CSR.pdf
description: An Open Label Trial of TMC114/Rtv in HIV-1 Infected Subjects Who Were Randomized in the Trials TMC114-C201, TMC114-C207 or in Sponsor Selected Phase I Trials
responsible party type: Sponsor
mesh term: Darunavir