<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/NCT02257008</url>
  </required_header>
  <id_info>
    <org_study_id>1188.6</org_study_id>
    <nct_id>NCT02257008</nct_id>
  </id_info>
  <brief_title>Effect of Different Boosting Agents on Pharmacokinetics of BILR 355 BS Dissolved in Polyethylene Glycol 400 (PEG 400) in Healthy Male Volunteers</brief_title>
  <official_title>An Open Study to Investigate the Effect of Different Boosting Agents on Pharmacokinetics of Single Doses of BILR 355 BS (Dose Steps: 5 and 12.5 mg) Dissolved in 5 mL PEG 400 After Oral Administration in Healthy Male Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Assessment of the effect of different boosting agents on pharmacokinetics of a single dose of&#xD;
      BILR 355 BS dissolved in PEG 400&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2003</start_date>
  <primary_completion_date type="Actual">December 2003</primary_completion_date>
  <phase>Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum observed concentration of the analyte in the plasma (Cmax)</measure>
    <time_frame>up to 120 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time from dosing to the maximum concentration of the analyte in plasma (tmax)</measure>
    <time_frame>up to 120 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma at different time points (AUC)</measure>
    <time_frame>up to 120 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent terminal half-life of the analyte in plasma (t1/2)</measure>
    <time_frame>up to 120 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent clearance of the analyte in plasma after extravascular multiple dose administration (CL/F)</measure>
    <time_frame>up to 120 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total mean residence time of the analyte in the body (MRTtot)</measure>
    <time_frame>up to 120 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent volume of distribution of the analyte during the terminal phase λz following extravascular administration (Vz/F)</measure>
    <time_frame>up to 120 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Renal clearance of the analyte determined over the dosing interval τ (CLR)</measure>
    <time_frame>up to 120 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Amount of the analyte excreted into urine (Ae)</measure>
    <time_frame>up to 72 hours after start of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinically relevant changes in laboratory parameters</measure>
    <time_frame>up to 10 days after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinically relevant changes in vital signs (blood pressure, pulse-, respiratory rate, body temperature)</measure>
    <time_frame>up to 10 days after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinically relevant changes in 12-lead ECG</measure>
    <time_frame>up to 10 days after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinically relevant changes in faecal occult blood testing</measure>
    <time_frame>up to 10 days after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>Up to 25 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global tolerability assessment by investigator on a 5-point scale</measure>
    <time_frame>Up to 10 days after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinically relevant changes in neurological assessment</measure>
    <time_frame>up to 10 days after start of treatment</time_frame>
    <description>Assessment of central nervous system function including Romberg's test, heel-to-toe straight line, and finger-nose tests</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Single rising dose of BILR 355 BS with grapefruit juice</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Single rising dose of BILR 355 BS with nelfinavir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Single dose of BILR 355 BS with atazanavir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Single dose of BILR 355 BS with atazanavir, ritonavir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BILR 355 BS</intervention_name>
    <arm_group_label>Single dose of BILR 355 BS with atazanavir</arm_group_label>
    <arm_group_label>Single dose of BILR 355 BS with atazanavir, ritonavir</arm_group_label>
    <arm_group_label>Single rising dose of BILR 355 BS with grapefruit juice</arm_group_label>
    <arm_group_label>Single rising dose of BILR 355 BS with nelfinavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Grapefruit juice</intervention_name>
    <arm_group_label>Single rising dose of BILR 355 BS with grapefruit juice</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nelfinavir</intervention_name>
    <arm_group_label>Single rising dose of BILR 355 BS with nelfinavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atazanavir</intervention_name>
    <arm_group_label>Single dose of BILR 355 BS with atazanavir</arm_group_label>
    <arm_group_label>Single dose of BILR 355 BS with atazanavir, ritonavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>Single dose of BILR 355 BS with atazanavir, ritonavir</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All participants in the study were to be healthy males, range from 21 to 50 years of&#xD;
             age and their body mass index (BMI) be within 18.5 to 29.9 kg/m2 (BMI calculation:&#xD;
             weight in kilograms divided by the square of height in meters)&#xD;
&#xD;
          -  In accordance with good clinical practice (GCP) and the local legislation all&#xD;
             volunteers had to give their written informed consent prior to admission to the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including blood pressure, pulse rate and ECG)&#xD;
             deviating from normal and of clinical relevance&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  History of orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of allergy/hypersensitivity (including drug allergy) which is deemed relevant&#xD;
             to the trial as judged by the investigator&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24 hours) within at least one month or less&#xD;
             than ten half-lives of the respective drug before enrolment in the study or during the&#xD;
             study&#xD;
&#xD;
          -  Use of any drugs which might influence the results of the trial up to 7 days prior to&#xD;
             enrolment in the study or during the study&#xD;
&#xD;
          -  Participation in another trial with an investigational drug (&lt;= two months prior to&#xD;
             administration or during the trial)&#xD;
&#xD;
          -  Smoker (&gt; 10 cigarettes or &gt; 3 cigars of &gt; 3 pipes/day)&#xD;
&#xD;
          -  Inability to refrain from smoking on trial days&#xD;
&#xD;
          -  Alcohol abuse (&gt; 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (&gt;= 100 mL within four weeks prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Any laboratory value outside the clinically accepted reference range&#xD;
&#xD;
          -  Excessive physical activities within the last week before the trial or during the&#xD;
             trial&#xD;
&#xD;
        Following exclusion criteria are of special interest for this study:&#xD;
&#xD;
          -  Erythema, exanthema and comparable skin alterations&#xD;
&#xD;
          -  For the boosting agents atazanavir and atazanavir plus ritonavir, subjects with a PQ&#xD;
             interval length in the screening ECG of &gt; 200 ms or any higher degree of&#xD;
             atrio-ventricular (AV) block were to be excluded&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <last_update_submitted>October 2, 2014</last_update_submitted>
  <last_update_submitted_qc>October 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 6, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Atazanavir Sulfate</mesh_term>
    <mesh_term>Nelfinavir</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/NCT02257008
org study id: 1188.6
nct id: NCT02257008
lead sponsor: 
Assessment of the effect of different boosting agents on pharmacokinetics of a single dose of
      BILR 355 BS dissolved in PEG 400
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum observed concentration of the analyte in the plasma (Cmax)
time frame: up to 120 hours after start of treatment
measure: Time from dosing to the maximum concentration of the analyte in plasma (tmax)
time frame: up to 120 hours after start of treatment
measure: Area under the concentration-time curve of the analyte in plasma at different time points (AUC)
time frame: up to 120 hours after start of treatment
measure: Apparent terminal half-life of the analyte in plasma (t1/2)
time frame: up to 120 hours after start of treatment
measure: Apparent clearance of the analyte in plasma after extravascular multiple dose administration (CL/F)
time frame: up to 120 hours after start of treatment
measure: Total mean residence time of the analyte in the body (MRTtot)
time frame: up to 120 hours after start of treatment
measure: Apparent volume of distribution of the analyte during the terminal phase λz following extravascular administration (Vz/F)
time frame: up to 120 hours after start of treatment
measure: Renal clearance of the analyte determined over the dosing interval τ (CLR)
time frame: up to 120 hours after start of treatment
measure: Amount of the analyte excreted into urine (Ae)
time frame: up to 72 hours after start of treatment
measure: Number of participants with clinically relevant changes in laboratory parameters
time frame: up to 10 days after start of treatment
measure: Number of participants with clinically relevant changes in vital signs (blood pressure, pulse-, respiratory rate, body temperature)
time frame: up to 10 days after start of treatment
measure: Number of participants with clinically relevant changes in 12-lead ECG
time frame: up to 10 days after start of treatment
measure: Number of participants with clinically relevant changes in faecal occult blood testing
time frame: up to 10 days after start of treatment
measure: Number of participants with adverse events
time frame: Up to 25 days
measure: Global tolerability assessment by investigator on a 5-point scale
time frame: Up to 10 days after start of treatment
measure: Number of participants with clinically relevant changes in neurological assessment
time frame: up to 10 days after start of treatment
description: Assessment of central nervous system function including Romberg's test, heel-to-toe straight line, and finger-nose tests
arm group label: Single rising dose of BILR 355 BS with grapefruit juice
arm group type: Experimental
arm group label: Single rising dose of BILR 355 BS with nelfinavir
arm group type: Experimental
arm group label: Single dose of BILR 355 BS with atazanavir
arm group type: Experimental
arm group label: Single dose of BILR 355 BS with atazanavir, ritonavir
arm group type: Experimental
intervention type: Drug
intervention name: BILR 355 BS
arm group label: Single dose of BILR 355 BS with atazanavir
arm group label: Single dose of BILR 355 BS with atazanavir, ritonavir
arm group label: Single rising dose of BILR 355 BS with grapefruit juice
arm group label: Single rising dose of BILR 355 BS with nelfinavir
intervention type: Other
intervention name: Grapefruit juice
arm group label: Single rising dose of BILR 355 BS with grapefruit juice
intervention type: Drug
intervention name: Nelfinavir
arm group label: Single rising dose of BILR 355 BS with nelfinavir
intervention type: Drug
intervention name: Atazanavir
arm group label: Single dose of BILR 355 BS with atazanavir
arm group label: Single dose of BILR 355 BS with atazanavir, ritonavir
intervention type: Drug
intervention name: Ritonavir
arm group label: Single dose of BILR 355 BS with atazanavir, ritonavir
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Ritonavir
mesh term: Atazanavir Sulfate
mesh term: Nelfinavir