<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/NCT02232581</url>
  </required_header>
  <id_info>
    <org_study_id>1211.1</org_study_id>
    <nct_id>NCT02232581</nct_id>
  </id_info>
  <brief_title>Study to Determine the Antiviral Activity and Safety of Alovudine in Nucleoside-experienced HIV-infected Subjects Experiencing Virologic Failure</brief_title>
  <official_title>Randomised, Double Blind, Placebo-controlled Dose Ranging Trial to Determine the Antiviral Activity and Safety of Alovudine in Nucleoside-experienced HIV-infected Subjects Experiencing Virologic Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The primary objective was to determine the mean change in HIV viral load from baseline to&#xD;
      Week 4 compared with placebo after 4 weeks of treatment in highly experienced HIV-infected&#xD;
      patients.&#xD;
&#xD;
      Secondary objectives were to determine (1) the tolerability, hematologic and hepatic safety&#xD;
      of different doses of alovudine and (2) the effect of baseline nucleoside genotypic&#xD;
      susceptibility on virologic response after 4 weeks of alovudine administration&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2004</start_date>
  <primary_completion_date type="Actual">December 2004</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean change in HIV viral load measured from plasma samples</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of virologic responders per treatment arm</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients experiencing a change of viral load</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
    <description>viral load of ≥1 log10 from baseline to Week 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in CD4+ cell count</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of 0.5 virologic responders per treatment arm</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of load responders per treatment arm</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of 0.7 to 0.9 virologic responders per treatment arm</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with laboratory test abnormalities and with respect to Division of AIDS (DAIDS) grading</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with serious adverse events</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients who discontinued due to adverse event</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in CD8+ cell count</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with abnormal changes in laboratory parameters</measure>
    <time_frame>Up to 4 weeks after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Alovudine - low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Alovudine - medium</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Alovudine - high</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alovudine - low</intervention_name>
    <arm_group_label>Alovudine - low</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alovudine - medium</intervention_name>
    <arm_group_label>Alovudine - medium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alovudine - high</intervention_name>
    <arm_group_label>Alovudine - high</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Alovudine - low</arm_group_label>
    <arm_group_label>Alovudine - medium</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent before any trial procedure&#xD;
&#xD;
          -  HIV-1 infected males or females ≥18 years of age&#xD;
&#xD;
          -  Screening genotypic resistance report indicating two or more of the following&#xD;
             nucleoside reverse transcriptase inhibitors (NRTI) resistance mutations: 41, 67, 70,&#xD;
             210 and 215&#xD;
&#xD;
          -  Stable NRTI regimen without stavudine and zidovudine for at least 6 weeks before&#xD;
             screening and stable antiretroviral (ARV) background treatment for 3 months before&#xD;
             screening&#xD;
&#xD;
          -  HIV-1 viral load ≥1000 copies/mL and &lt;75,000 copies/mL at screening&#xD;
&#xD;
          -  Change in viral load between previous test within 3 months before screening, using&#xD;
             local laboratory for routine tests, and screening test was &lt;1.0 log10 copies/mL&#xD;
&#xD;
          -  Acceptable medical history, as assessed by the investigator&#xD;
&#xD;
          -  Current stable ARV medication regimen between screening (Visit 1) and Visit 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ARV medication naïve&#xD;
&#xD;
          -  Patients on recent drug holiday, defined as off ARV medications for at least 7&#xD;
             consecutive days within the previous 3 months&#xD;
&#xD;
          -  Female patients of child-bearing potential who :&#xD;
&#xD;
               -  have a positive serum pregnancy test&#xD;
&#xD;
               -  are breast feeding,&#xD;
&#xD;
               -  are planning to become pregnant, or&#xD;
&#xD;
               -  are not willing to use a barrier method of contraception&#xD;
&#xD;
          -  Prior alovudine use&#xD;
&#xD;
          -  Use of investigational medications within 30 days before study entry or during the&#xD;
             trial&#xD;
&#xD;
          -  Use of immunomodulatory drugs within 3 months before study entry or during the trial&#xD;
             (e.g. interferon, cyclosporine, hydroxyurea, interleukin-2)&#xD;
&#xD;
          -  Current use of rifampin, rifabutine, isoniazid, pyrazinamide, stavudine, zidovudine,&#xD;
             ganciclovir, chronic use of hepatotoxic drugs, anti-tumour therapy or probenecid&#xD;
&#xD;
          -  Laboratory values:&#xD;
&#xD;
               -  Neutrophils of Grade 2 or greater abnormality&#xD;
&#xD;
               -  Hemoglobin of Grade 2 or greater abnormality&#xD;
&#xD;
               -  Platelets: Grade 2 or greater abnormality&#xD;
&#xD;
               -  Creatinine of ≥1.25 Upper limit of the normal (ULN)&#xD;
&#xD;
               -  Lipase of Grade 1 or greater abnormality&#xD;
&#xD;
               -  Alanine aminotransaminase (ALT) or Aspartate aminotransaminase (AST) of Grade 2&#xD;
                  or greater abnormality&#xD;
&#xD;
               -  Direct bilirubin of Grade 1 or greater abnormality&#xD;
&#xD;
          -  CD4 ≤50 cells/mm3&#xD;
&#xD;
          -  Hepatitis B (+HBsAg or +HBcAB) or C +Hepatitis C virus (+HCV AB ) co-infection,&#xD;
             chronic hepatitis, on-going hepatitis or pancreatitis&#xD;
&#xD;
          -  Any new or active AIDS-defining event within 30 days before study entry&#xD;
&#xD;
          -  Inability to adhere to the requirements of the protocol, including active substance&#xD;
             abuse as assessed by the investigator&#xD;
&#xD;
          -  In the opinion of the investigator, likely survival of less than 6 months because of&#xD;
             underlying disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>September 4, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>September 4, 2014</last_update_submitted>
  <last_update_submitted_qc>September 4, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 5, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alovudine</mesh_term>
    <mesh_term>Dideoxynucleosides</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/NCT02232581
org study id: 1211.1
nct id: NCT02232581
lead sponsor: 
The primary objective was to determine the mean change in HIV viral load from baseline to
      Week 4 compared with placebo after 4 weeks of treatment in highly experienced HIV-infected
      patients.

      Secondary objectives were to determine (1) the tolerability, hematologic and hepatic safety
      of different doses of alovudine and (2) the effect of baseline nucleoside genotypic
      susceptibility on virologic response after 4 weeks of alovudine administration
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Mean change in HIV viral load measured from plasma samples
time frame: Up to 4 weeks after drug administration
measure: Percentage of virologic responders per treatment arm
time frame: Up to 4 weeks after drug administration
measure: Proportion of patients experiencing a change of viral load
time frame: Up to 4 weeks after drug administration
description: viral load of ≥1 log10 from baseline to Week 4
measure: Mean change in CD4+ cell count
time frame: Up to 4 weeks after drug administration
measure: Percentage of 0.5 virologic responders per treatment arm
time frame: Up to 4 weeks after drug administration
measure: Percentage of load responders per treatment arm
time frame: Up to 4 weeks after drug administration
measure: Percentage of 0.7 to 0.9 virologic responders per treatment arm
time frame: Up to 4 weeks after drug administration
measure: Number of patients with adverse events
time frame: Up to 4 weeks after drug administration
measure: Number of patients with laboratory test abnormalities and with respect to Division of AIDS (DAIDS) grading
time frame: Up to 4 weeks after drug administration
measure: Number of patients with serious adverse events
time frame: Up to 4 weeks after drug administration
measure: Number of patients who discontinued due to adverse event
time frame: Up to 4 weeks after drug administration
measure: Mean change in CD8+ cell count
time frame: Up to 4 weeks after drug administration
measure: Number of patients with abnormal changes in laboratory parameters
time frame: Up to 4 weeks after drug administration
arm group label: Alovudine - low
arm group type: Experimental
arm group label: Alovudine - medium
arm group type: Experimental
arm group label: Alovudine - high
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Alovudine - low
arm group label: Alovudine - low
intervention type: Drug
intervention name: Alovudine - medium
arm group label: Alovudine - medium
intervention type: Drug
intervention name: Alovudine - high
arm group label: Alovudine - high
intervention type: Drug
intervention name: Placebo
arm group label: Alovudine - low
arm group label: Alovudine - medium
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Alovudine
mesh term: Dideoxynucleosides