<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/NCT02202005</url>
  </required_header>
  <id_info>
    <org_study_id>NEVIR5U14EU</org_study_id>
    <secondary_id>2014-002247-18</secondary_id>
    <nct_id>NCT02202005</nct_id>
  </id_info>
  <brief_title>Multiple Dose BE Study With Nevirapine 400mg PR Tablets</brief_title>
  <official_title>A Multiple Dose, Open Label, Pivotal, 4 Period, 2 Treatment, Sequence Full Replicative Crossover Study to Assess the Bioequivalence (BE) of TEVA's Generic Once Daily Nevirapine 400 mg Prolonged Release (PR) Formulation Compared With the Approved Reference Product Viramune® 400 mg Prolonged Release Tablets Under Fasted Conditions in HIV1 Infected Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ratiopharm GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Teva Branded Pharmaceutical Products R&amp;D, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this steady state pivotal study is to compare the rate and extent of&#xD;
      absorption and to evaluate Bioequivalence of test drug compared to the approved reference&#xD;
      product in HIV infected individuals&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma concentrations by AUC0 τ,ss (area under the concentration time curve)</measure>
    <time_frame>Days 14, 28, 42, 56</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cτ,ss (defined as concentration at the end of dosing interval)</measure>
    <time_frame>Days 14, 28, 42, 56</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,ss (maximum observed plasma concentration)</measure>
    <time_frame>Days 14, 28, 42, 56</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of fluctuation over one dosing interval at steady state (Fl(%)</measure>
    <time_frame>Days 14, 28, 42, 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax,ss (the time to maximum plasma concentration at steady state)</measure>
    <time_frame>Days 14, 28, 42, 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin,ss (minimum plasma concentration at steady state)</measure>
    <time_frame>Days 14, 28, 42, 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average plasma drug concentration</measure>
    <time_frame>Days 14, 28, 42, 56</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>HIV-1</condition>
  <arm_group>
    <arm_group_label>Nevirapine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Viramune®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nevirapine</intervention_name>
    <description>Nevirapine 400mg PR tablet</description>
    <arm_group_label>Nevirapine</arm_group_label>
    <arm_group_label>Viramune®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Viramune®</intervention_name>
    <description>Viramune® 400 mg Retardtabletten</description>
    <arm_group_label>Nevirapine</arm_group_label>
    <arm_group_label>Viramune®</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed and dated written informed consent prior to admission to the study&#xD;
&#xD;
          2. HIV1 infected males or females of 18 to 65 years, nonsmoker (use of cannabis may be&#xD;
             accepted)&#xD;
&#xD;
          3. Body weight ≥ 50.0 kg and BMI ≥ 18.0 and ≤ 32.0 kg/m2&#xD;
&#xD;
          4. Absence of clinically significant history of neurological, endocrinal, cardiovascular,&#xD;
             pulmonary, haematological, psychiatric, gastrointestinal, renal, hepatic, obstructive&#xD;
             disorders, cholestasis, and metabolic disease&#xD;
&#xD;
          5. Treatment with a stable nevirapine based combination regimen for at least the&#xD;
             preceding 12 weeks (or 6 weeks if switched from an antiretroviral regimen containing&#xD;
             two nucleoside analogues and efavirenz)&#xD;
&#xD;
          6. Background HIV therapy with a stable antiretroviral regimen that is recommended in&#xD;
             combination with nevirapine according to British HIV Association clinical guidelines:&#xD;
&#xD;
               1. Abacavir and lamivudine {ABC/3TC} as fixed dose combination Kivexa&#xD;
&#xD;
               2. Tenofovir and emtricitabine {TDF/FTC} Truvada&#xD;
&#xD;
               3. Zidovudine and lamivudine {AZT/3TC} - Combivir, OR&#xD;
&#xD;
               4. Tenofovir and lamivudine as separately prescribed components and kept constant&#xD;
                  (in combination and dosage) throughout the whole course of the study&#xD;
&#xD;
          7. An HIV viral load &lt; 50 copies/mL in preceding 3 months and at screening&#xD;
&#xD;
          8. A CD4+ Tcell count &gt; 50 cell/mm3&#xD;
&#xD;
          9. Acceptable screening laboratory values that indicate adequate baseline organ function&#xD;
&#xD;
         10. Willingness to abstain from ingesting medications that are listed as contraindicated&#xD;
             for nevirapine during the whole course of the study&#xD;
&#xD;
         11. Capable of completing patient diaries&#xD;
&#xD;
         12. Capable and willing to come back for PK assessments and follow up&#xD;
&#xD;
         13. Willingness to refrain from excessive physical activity during the trial&#xD;
&#xD;
         14. Willingness of male study participants to not father a child during and throughout the&#xD;
             study. To prevent a pregnancy of the female partner, both the male study participant&#xD;
             and the female partner need to take appropriate contraceptives to prevent pregnancy&#xD;
             during the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Infection with HIV2 or HIV1 group O.&#xD;
&#xD;
          2. Current treatment with an HIV protease inhibitor&#xD;
&#xD;
          3. Participation in any other study within 30 days of Day 1, or intention to participate&#xD;
             in another study during participation in this study.&#xD;
&#xD;
          4. Male and female patients who are not willing to use male or female condoms to prevent&#xD;
             HIV transmission&#xD;
&#xD;
          5. Female patients of childbearing potential who:&#xD;
&#xD;
               1. Have a positive serum pregnancy test at screening.&#xD;
&#xD;
               2. Are breast feeding.&#xD;
&#xD;
               3. Are planning to become pregnant&#xD;
&#xD;
               4. Are not willing to take appropriate measures to prevent pregnancy during the&#xD;
                  study&#xD;
&#xD;
          6. Females who do not use an acceptable contraceptive regimen or confirm total abstinence&#xD;
             will be allowed to participate in this study only if they are not considered to be of&#xD;
             childbearing potential&#xD;
&#xD;
          7. Laboratory parameters &gt; DAIDS grade 2 Coagulation&#xD;
&#xD;
          8. Laboratory parameters &gt; DAIDS grade 2 Total triglycerides&#xD;
&#xD;
          9. Hypersensitivity to the active substance or any ingredients of the test or reference&#xD;
             investigational products or chemically related compounds.&#xD;
&#xD;
         10. Contraindication to Nevirapine&#xD;
&#xD;
         11. Relevant history or current condition, illness that might interfere with drug&#xD;
             absorption, distribution, metabolism or excretion&#xD;
&#xD;
         12. Use of concomitant medication (other than the stable background antiretroviral HIV&#xD;
             therapy) that may interfere with the pharmacokinetics of nevirapine and/or the&#xD;
             background antiretroviral HIV therapy)&#xD;
&#xD;
         13. Intake of products containing St. John's Wort from 14 days before treatment with study&#xD;
             medication (Day 1) and not willing to abstain from it throughout the study until after&#xD;
             the last study visit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Teva Medical Expert, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chelsea and Westminster NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chelsea and Westminster NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SW10 9TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>August 21, 2015</last_update_submitted>
  <last_update_submitted_qc>August 21, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 25, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bioequivalence</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nevirapine</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/NCT02202005
org study id: NEVIR5U14EU
secondary id: 2014-002247-18
nct id: NCT02202005
lead sponsor: 
has dmc: No
The objective of this steady state pivotal study is to compare the rate and extent of
      absorption and to evaluate Bioequivalence of test drug compared to the approved reference
      product in HIV infected individuals
allocation: Non-Randomized
intervention model: Crossover Assignment
masking: None (Open Label)
measure: Plasma concentrations by AUC0 τ,ss (area under the concentration time curve)
time frame: Days 14, 28, 42, 56
measure: Cτ,ss (defined as concentration at the end of dosing interval)
time frame: Days 14, 28, 42, 56
measure: Cmax,ss (maximum observed plasma concentration)
time frame: Days 14, 28, 42, 56
measure: Percentage of fluctuation over one dosing interval at steady state (Fl(%)
time frame: Days 14, 28, 42, 56
measure: Tmax,ss (the time to maximum plasma concentration at steady state)
time frame: Days 14, 28, 42, 56
measure: Cmin,ss (minimum plasma concentration at steady state)
time frame: Days 14, 28, 42, 56
measure: Average plasma drug concentration
time frame: Days 14, 28, 42, 56
arm group label: Nevirapine
arm group type: Experimental
arm group label: Viramune®
arm group type: Active Comparator
intervention type: Drug
intervention name: Nevirapine
description: Nevirapine 400mg PR tablet
arm group label: Nevirapine
arm group label: Viramune®
intervention type: Drug
intervention name: Viramune®
description: Viramune® 400 mg Retardtabletten
arm group label: Nevirapine
arm group label: Viramune®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Teva Medical Expert, MD
role: Principal Investigator
affiliation: Chelsea and Westminster NHS Foundation Trust
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Nevirapine