<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/NCT02211482</url>
  </required_header>
  <id_info>
    <org_study_id>FH-18</org_study_id>
    <nct_id>NCT02211482</nct_id>
  </id_info>
  <brief_title>Dolutegravir-Lamivudine as Dual Therapy in Naive HIV-Infected Patients: A Pilot Study</brief_title>
  <acronym>PADDLE</acronym>
  <official_title>Dolutegravir-Lamivudine as Dual Therapy in Naive HIV-Infected Patients: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación Huésped</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ViiV Healthcare</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundación Huésped</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the antiviral efficacy, safety and tolerability of&#xD;
      dual therapy with 3TC and DTG as initial therapy among naïve HIV patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to compare the antiviral efficacy, safety and tolerability of&#xD;
      dual therapy with 3TC and DTG as initial therapy among naïve HIV patients.&#xD;
&#xD;
      Data collected in this study would inform the development of larger studies designed to&#xD;
      evaluate metabolic and long term safety, impact on inflammatory biomarkers, efficacy, safety&#xD;
      and cost effectiveness of this strategy among naïve and suppressed patients.&#xD;
&#xD;
      Primary endpoint:Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL at&#xD;
      week 48.&#xD;
&#xD;
      Secondary endpoints: Frequency, type and severity of adverse events and laboratory&#xD;
      abnormalities, Proportion of patients with HIV-1 RNA &lt;1000 copies/mL at week 12, Proportion&#xD;
      of patients with HIV-RNA &lt;400 at week 24 Number and type of resistance mutations in case of&#xD;
      virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL&#xD;
      or viral rebound at any timepoint) Changes in CD4+ lymphocyte count between baseline and 48&#xD;
      weeks, Estimation of the viral decay compared to historical data.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">April 2017</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 4</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>Efficacy Outcome Measure</measure>
    <time_frame>48 weeks</time_frame>
    <description>Percentage of Participants with HIV-1 RNA levels of less than 50 copies/mL at week 48 by ITT analysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>safety</measure>
    <time_frame>48 week</time_frame>
    <description>Frequency, type and severity of adverse events and laboratory abnormalities</description>
  </secondary_outcome>
  <other_outcome>
    <measure>efficacy</measure>
    <time_frame>24 weeks</time_frame>
    <description>Proportion of patients with HIV-RNA &lt;400 at week 24</description>
  </other_outcome>
  <other_outcome>
    <measure>safety</measure>
    <time_frame>48 weeks</time_frame>
    <description>change in lipid profile between baseline and week 48.</description>
  </other_outcome>
  <other_outcome>
    <measure>efficacy</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of patients with HIV-1 RNA &lt;1000 copies/mL at week 12</description>
  </other_outcome>
  <other_outcome>
    <measure>Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint)</description>
  </other_outcome>
  <other_outcome>
    <measure>efficacy</measure>
    <time_frame>48 weeks</time_frame>
    <description>Changes in CD4+ lymphocyte count between baseline and 48 weeks</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>HIV-1 Infection</condition>
  <arm_group>
    <arm_group_label>Dolutegravir , lamivudine</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Dolutegravir 50 mg QD plus lamivudine 300 mg QD</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dolutegravir, lamivudine</intervention_name>
    <description>single arm</description>
    <arm_group_label>Dolutegravir , lamivudine</arm_group_label>
    <other_name>dolutegravir</other_name>
    <other_name>lamivudine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. &gt; 18 years of age&#xD;
&#xD;
          2. Documented HIV-1 infection (positive ELISA plus a confirmatory Western Blot; or plasma&#xD;
             HIV-1 RNA ≥10,000 copies/mL)&#xD;
&#xD;
          3. Voluntarily signed and dated , IRB / IEC approved informed consent form&#xD;
&#xD;
          4. Agrees not to take any other medication during the study&#xD;
&#xD;
          5. Screening HIV RNA &gt;5,000 copies/mL and ≤ 100,000 copies/ml&#xD;
&#xD;
          6. Naïve to ARV therapies&#xD;
&#xD;
          7. CD4 ≥200 cells/mL&#xD;
&#xD;
          8. Subjects can comply with protocol requirements&#xD;
&#xD;
          9. Subject's general medical condition, in the investigator's opinion, does not interfere&#xD;
             with assessments and completion of the trial&#xD;
&#xD;
         10. Patient is a male or a female not breastfeeding or pregnant&#xD;
&#xD;
         11. A female, may be eligible if she:&#xD;
&#xD;
               1. is of non-child-bearing potential&#xD;
&#xD;
               2. is of child-bearing potential with a negative pregnancy test at Screening and Day&#xD;
                  1 and agrees to use one of the following methods:&#xD;
&#xD;
                    -  Complete abstinence from penile-vaginal intercourse from 2 weeks prior to&#xD;
                       administration of IP, throughout the study, and for at least 2 weeks after&#xD;
&#xD;
                    -  Double barrier method (male condom/spermicide, male condom/diaphragm,&#xD;
                       diaphragm/spermicide)&#xD;
&#xD;
                    -  IUD and male condom&#xD;
&#xD;
                    -  Male partner sterilization confirmed and male condom&#xD;
&#xD;
                    -  Approved hormonal contraception and male condom&#xD;
&#xD;
                    -  Any other method with published data showing that the expected failure rate&#xD;
                       is &lt;1% per year and use male condom&#xD;
&#xD;
                    -  Any contraception method must be used for at least 2 weeks after&#xD;
                       discontinuation of IP&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Genotypic resistance to lamivudine at screening,as per IAS -USA Panel 2013 2. Alcohol or&#xD;
        drug use that might impact on adherence 3. Subjects positive for Hepatitis B at screening&#xD;
        (+HBsAg), or anticipated need for Hepatitis C virus (HCV) therapy during the study 4.&#xD;
        Lactating, pregnancy or fertile women willing to be pregnant 5. Concomitant use of lowering&#xD;
        lipid drugs, interferon, interleukin-2, cytotoxic chemotherapy, Dofetilide (or pilsicainide&#xD;
        ) or immunosuppressors at study entry 6. Grade 4 lab abnormalities 7. Primary HIV infection&#xD;
        (indeterminate WB or previous negative HIV in the last 6 months.) 8. Opportunistic&#xD;
        infection (CDC C category) or other disease and/or clinical condition that, in the&#xD;
        investigator's opinion, would compromise the patient's safety or outcome of the study;&#xD;
        including malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or&#xD;
        resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial&#xD;
        neoplasia 9. Subjects who in the investigator's judgment, poses a significant suicidality&#xD;
        risk 10. History or presence of allergy to the study drugs or their components or drugs of&#xD;
        their class 11. Treatment with any of the following agents within 28 days of Screening:&#xD;
        radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter&#xD;
        immune responses or treatment with an HIV-1 immunotherapeutic vaccine within 90 days of&#xD;
        Screening or exposure to an experimental drug or experimental vaccine within either 28&#xD;
        days, 5 half-lives of the test agent, or twice the duration of the biological effect of the&#xD;
        test agent, whichever is longer, prior to the first dose of investigational product 12. Any&#xD;
        acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would&#xD;
        preclude the subject's participation in the study of an investigational compound 13.&#xD;
        Alanine aminotransferase (ALT) &gt;5 times the upper limit of normal (ULN), or ALT ≥ 3xULN and&#xD;
        bilirubin ≥ 1.5xULN (with &gt;35% direct bilirubin) 14. Creatinine clearance of &lt;50 mL/min via&#xD;
        Cockcroft-Gault method 15. Subjects with moderate to severe hepatic impairment (Class B or&#xD;
        greater) as determined by Child-Pugh classification&#xD;
&#xD;
        -&#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>Pedro Cahn, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundacion Huesped</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fundacion Huesped</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1202ABB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>August 10, 2017</last_update_submitted>
  <last_update_submitted_qc>August 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fundación Huésped</investigator_affiliation>
    <investigator_full_name>Pedro Cahn</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>HIV-1 infected patients</keyword>
  <keyword>dual therapy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lamivudine</mesh_term>
    <mesh_term>Dolutegravir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>to publish week 48 study results</ipd_description>
  </patient_data>
  <!-- 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/NCT02211482
org study id: FH-18
nct id: NCT02211482
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate the antiviral efficacy, safety and tolerability of
      dual therapy with 3TC and DTG as initial therapy among naïve HIV patients
The purpose of this study is to compare the antiviral efficacy, safety and tolerability of
      dual therapy with 3TC and DTG as initial therapy among naïve HIV patients.

      Data collected in this study would inform the development of larger studies designed to
      evaluate metabolic and long term safety, impact on inflammatory biomarkers, efficacy, safety
      and cost effectiveness of this strategy among naïve and suppressed patients.

      Primary endpoint:Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL at
      week 48.

      Secondary endpoints: Frequency, type and severity of adverse events and laboratory
      abnormalities, Proportion of patients with HIV-1 RNA <1000 copies/mL at week 12, Proportion
      of patients with HIV-RNA <400 at week 24 Number and type of resistance mutations in case of
      virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL
      or viral rebound at any timepoint) Changes in CD4+ lymphocyte count between baseline and 48
      weeks, Estimation of the viral decay compared to historical data.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy Outcome Measure
time frame: 48 weeks
description: Percentage of Participants with HIV-1 RNA levels of less than 50 copies/mL at week 48 by ITT analysis
measure: safety
time frame: 48 week
description: Frequency, type and severity of adverse events and laboratory abnormalities
measure: efficacy
time frame: 24 weeks
description: Proportion of patients with HIV-RNA <400 at week 24
measure: safety
time frame: 48 weeks
description: change in lipid profile between baseline and week 48.
measure: efficacy
time frame: 12 weeks
description: Proportion of patients with HIV-1 RNA <1000 copies/mL at week 12
measure: Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint)
time frame: 48 weeks
description: Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint)
measure: efficacy
time frame: 48 weeks
description: Changes in CD4+ lymphocyte count between baseline and 48 weeks
arm group label: Dolutegravir , lamivudine
arm group type: Other
description: Dolutegravir 50 mg QD plus lamivudine 300 mg QD
intervention type: Drug
intervention name: dolutegravir, lamivudine
description: single arm
arm group label: Dolutegravir , lamivudine
other name: dolutegravir
other name: lamivudine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pedro Cahn, PhD
role: Principal Investigator
affiliation: Fundacion Huesped
facility: 
country: Argentina
responsible party type: Principal Investigator
investigator affiliation: Fundación Huésped
investigator full name: Pedro Cahn
investigator title: PhD
mesh term: Lamivudine
mesh term: Dolutegravir
sharing ipd: Yes
ipd description: to publish week 48 study results