<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/NCT02194179</url>
  </required_header>
  <id_info>
    <org_study_id>1100.1489</org_study_id>
    <nct_id>NCT02194179</nct_id>
  </id_info>
  <brief_title>Bioavailability of 2 Different Nevirapine Extended Release Formulations Compared to Viramune® in HIV-1 Infected Subjects</brief_title>
  <official_title>Steady State Bioavailability of 2 Different Nevirapine Extended Release Formulations Compared to Steady State 400 mg of Viramune® (200 mg BID), in HIV-1 Infected Subjects, an Open Label, Non Randomised, Multidose and Multistage Parallel Group Study. (ERVIR)</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 objective was to establish the pharmacokinetic (PK) profile at steady state of two&#xD;
      different nevirapine (NVP) extended release (XR) formulations at 300 mg or 400 mg daily (QD)&#xD;
      under fasted and fed conditions in comparison with the commercially available NVP immediate&#xD;
      release (IR) tablet at 200 mg BID (400 mg/day).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2006</start_date>
  <primary_completion_date type="Actual">May 2007</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time dosing interval τ)</measure>
    <time_frame>up to day 22</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over the time dosing interval τ)</measure>
    <time_frame>up to day 22</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over the time dosing interval τ)</measure>
    <time_frame>up to day 22</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax,ss / Cmin,ss ratio</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>%PTF (percentage peak-trough fluctuation)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax,ss (time from dosing to the maximum concentration of the analyte in plasma at steady state over the time dosing interval τ)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cavg (average measured concentration of the analyte in plasma at steady state)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events (AEs)</measure>
    <time_frame>up to day 57</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in clinical laboratory tests</measure>
    <time_frame>Baseline, up to day 37</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with abnormal detectable viral load</measure>
    <time_frame>Baseline, up to day 37</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in vital signs (blood pressure, pulse rate)</measure>
    <time_frame>Baseline, up to day 37</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in 12-lead electrocardiogram (ECG)</measure>
    <time_frame>Baseline, day 23</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in physical examination</measure>
    <time_frame>Baseline, up to day 37</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by the investigator on a 4-point scale</measure>
    <time_frame>up to day 37</time_frame>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">92</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>NVP XR 400 mg (KCR 25%) fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NVP XR 400 mg (KCR 25%) fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NVP XR 400 mg (KCR 20%) fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NVP XR 400 mg (KCR 20%) fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NVP XR 300 mg (KCR 25%) fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NVP XR 300 mg (KCR 25%) fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NVP XR 300 mg (KCR 20%) fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NVP XR 300 mg (KCR 20%) fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>NVP IR 200 mg (Viramune®)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NVP XR 400 mg (KCR 25%)</intervention_name>
    <arm_group_label>NVP XR 400 mg (KCR 25%) fasted</arm_group_label>
    <arm_group_label>NVP XR 400 mg (KCR 25%) fed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NVP XR 400 mg (KCR 20%)</intervention_name>
    <arm_group_label>NVP XR 400 mg (KCR 20%) fasted</arm_group_label>
    <arm_group_label>NVP XR 400 mg (KCR 20%) fed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NVP XR 300 mg (KCR 25%)</intervention_name>
    <arm_group_label>NVP XR 300 mg (KCR 25%) fasted</arm_group_label>
    <arm_group_label>NVP XR 300 mg (KCR 25%) fed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NVP XR 300 mg (KCR 20%)</intervention_name>
    <arm_group_label>NVP XR 300 mg (KCR 20%) fasted</arm_group_label>
    <arm_group_label>NVP XR 300 mg (KCR 20%) fed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>high-fat breakfast</intervention_name>
    <arm_group_label>NVP XR 300 mg (KCR 20%) fed</arm_group_label>
    <arm_group_label>NVP XR 300 mg (KCR 25%) fed</arm_group_label>
    <arm_group_label>NVP XR 400 mg (KCR 20%) fed</arm_group_label>
    <arm_group_label>NVP XR 400 mg (KCR 25%) fed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NVP IR 200 mg (Viramune®)</intervention_name>
    <arm_group_label>NVP IR 200 mg (Viramune®)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-1 infected males or females ≥ 18 and ≤ 60 years of age&#xD;
&#xD;
          -  Body mass index 18.5 to 29.9 kg/m2, inclusive&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice and local legislation&#xD;
&#xD;
          -  Treated with a stable Viramune® BID based regimen since at least 12 weeks prior to&#xD;
             study entry. If however, the subject's current Viramune® treatment consists of two&#xD;
             200mg tablets once daily (prescribed off label), the subject is allowed to participate&#xD;
             if he/she agrees to switch to Viramune® 200mg twice daily, 14 days before the start of&#xD;
             Nevirapine Extended Release.&#xD;
&#xD;
          -  An HIV-1 viral load of ≤ 50 c/mL at screening&#xD;
&#xD;
          -  Acceptable screening laboratory values that indicate adequate baseline organ function&#xD;
             with the following exceptions:&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)&#xD;
&#xD;
                  ≤2.5 times the upper limit of normal (ULN) (DAIDS Grade 1) or&#xD;
&#xD;
               -  Gamma-glutamyl transferase (GGT) &lt;2.5 times ULN (DAIDS Grade 1)&#xD;
&#xD;
          -  Willingness to abstain from alcoholic beverages for 24 hours prior to intensive&#xD;
             pharmakokinetic sampling days&#xD;
&#xD;
          -  Willingness to abstain from ingesting substances which may alter drug plasma levels by&#xD;
             interaction with the cytochrome P450 system during the study&#xD;
&#xD;
          -  Willingness to abstain from grapefruit and grapefruit juice, Seville oranges and&#xD;
             juice, and St John's wort or milk thistle starting 14 days prior to administration of&#xD;
             study medication until the end of the study, and&#xD;
&#xD;
          -  Karnofsky performance score ≥70&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current treatment with any PI&#xD;
&#xD;
          -  Participation in another trial with an investigational medicine within two months&#xD;
             prior to Day 1 of this study&#xD;
&#xD;
          -  Serum creatinine levels &gt;1.5 times ULN at screening&#xD;
&#xD;
          -  History of acute illness within 60 days prior to Day 1, which would make the subject,&#xD;
             in the opinion of the investigator, unsuitable for the trial&#xD;
&#xD;
          -  History or evidence of severe illness, malignancy or any other conditions which would&#xD;
             make the subjects, in the opinion of the investigator, unsuitable for the trial&#xD;
&#xD;
          -  Any evidence of a clinically relevant concomitant disease, including gastrointestinal,&#xD;
             hepatic, renal disorders of clinical relevance&#xD;
&#xD;
          -  Surgery of the gastrointestinal tract (except appendectomy and herniotomy)&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  Chronic or relevant acute infections other than HIV-1 (e.g. hepatitis B virus (HBV),&#xD;
             hepatitis C virus (HCV) co infection: A chronic or acute HBV infections is defined as:&#xD;
             HBs Ag positive. Chronic or acute HCV infection is defined as: HCV Ab positive and 1&#xD;
             confirmed positive viral load measurement preceding study entry)&#xD;
&#xD;
          -  Alcohol or substance abuse within 6 months prior to screening or during the study&#xD;
&#xD;
          -  Inability to comply with protocol requirements&#xD;
&#xD;
          -  Screening laboratory values &lt;DAIDS grade 1&#xD;
&#xD;
          -  All fertile males or females, and their respective partner(s) not willing to use two&#xD;
             forms of effective contraception. A double-barrier method must be used. A&#xD;
             double-barrier method is defined as e.g.: 1) a condom with spermicidal jelly or with a&#xD;
             foam suppository; 2) a diaphragm with spermicide; or 3) a male condom and a diaphragm&#xD;
&#xD;
          -  Female of child-bearing potential who:&#xD;
&#xD;
               -  Has a positive serum pregnancy test at screening,&#xD;
&#xD;
               -  Is breastfeeding,&#xD;
&#xD;
               -  Is planning to become pregnant, or&#xD;
&#xD;
               -  Is not willing to use barrier method protection or require ethinyl estradiol&#xD;
                  administration&#xD;
&#xD;
          -  Any AIDS-defining illness that is unresolved, symptomatic, or not stable on treatment&#xD;
             for at least 12 weeks before the screening visit&#xD;
&#xD;
          -  HIV-2 infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1100/1100.1489_U08-2197-01.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <last_update_submitted>July 17, 2014</last_update_submitted>
  <last_update_submitted_qc>July 17, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 18, 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>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/NCT02194179
org study id: 1100.1489
nct id: NCT02194179
lead sponsor: 
The objective was to establish the pharmacokinetic (PK) profile at steady state of two
      different nevirapine (NVP) extended release (XR) formulations at 300 mg or 400 mg daily (QD)
      under fasted and fed conditions in comparison with the commercially available NVP immediate
      release (IR) tablet at 200 mg BID (400 mg/day).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time dosing interval τ)
time frame: up to day 22
measure: Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over the time dosing interval τ)
time frame: up to day 22
measure: Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over the time dosing interval τ)
time frame: up to day 22
measure: Cmax,ss / Cmin,ss ratio
time frame: up to day 22
measure: %PTF (percentage peak-trough fluctuation)
time frame: up to day 22
measure: tmax,ss (time from dosing to the maximum concentration of the analyte in plasma at steady state over the time dosing interval τ)
time frame: up to day 22
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)
time frame: up to day 22
measure: Cavg (average measured concentration of the analyte in plasma at steady state)
time frame: up to day 22
measure: Number of patients with adverse events (AEs)
time frame: up to day 57
measure: Number of patients with clinically relevant changes in clinical laboratory tests
time frame: Baseline, up to day 37
measure: Number of patients with abnormal detectable viral load
time frame: Baseline, up to day 37
measure: Number of patients with clinically relevant changes in vital signs (blood pressure, pulse rate)
time frame: Baseline, up to day 37
measure: Number of patients with clinically relevant changes in 12-lead electrocardiogram (ECG)
time frame: Baseline, day 23
measure: Number of patients with clinically relevant changes in physical examination
time frame: Baseline, up to day 37
measure: Assessment of tolerability by the investigator on a 4-point scale
time frame: up to day 37
arm group label: NVP XR 400 mg (KCR 25%) fasted
arm group type: Experimental
arm group label: NVP XR 400 mg (KCR 25%) fed
arm group type: Experimental
arm group label: NVP XR 400 mg (KCR 20%) fasted
arm group type: Experimental
arm group label: NVP XR 400 mg (KCR 20%) fed
arm group type: Experimental
arm group label: NVP XR 300 mg (KCR 25%) fasted
arm group type: Experimental
arm group label: NVP XR 300 mg (KCR 25%) fed
arm group type: Experimental
arm group label: NVP XR 300 mg (KCR 20%) fasted
arm group type: Experimental
arm group label: NVP XR 300 mg (KCR 20%) fed
arm group type: Experimental
arm group label: NVP IR 200 mg (Viramune®)
arm group type: Active Comparator
intervention type: Drug
intervention name: NVP XR 400 mg (KCR 25%)
arm group label: NVP XR 400 mg (KCR 25%) fasted
arm group label: NVP XR 400 mg (KCR 25%) fed
intervention type: Drug
intervention name: NVP XR 400 mg (KCR 20%)
arm group label: NVP XR 400 mg (KCR 20%) fasted
arm group label: NVP XR 400 mg (KCR 20%) fed
intervention type: Drug
intervention name: NVP XR 300 mg (KCR 25%)
arm group label: NVP XR 300 mg (KCR 25%) fasted
arm group label: NVP XR 300 mg (KCR 25%) fed
intervention type: Drug
intervention name: NVP XR 300 mg (KCR 20%)
arm group label: NVP XR 300 mg (KCR 20%) fasted
arm group label: NVP XR 300 mg (KCR 20%) fed
intervention type: Other
intervention name: high-fat breakfast
arm group label: NVP XR 300 mg (KCR 20%) fed
arm group label: NVP XR 300 mg (KCR 25%) fed
arm group label: NVP XR 400 mg (KCR 20%) fed
arm group label: NVP XR 400 mg (KCR 25%) fed
intervention type: Drug
intervention name: NVP IR 200 mg (Viramune®)
arm group label: NVP IR 200 mg (Viramune®)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1100/1100.1489_U08-2197-01.pdf
description: Related Info
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Nevirapine